Wang is engaged in the research of nanotechnology and information storage, including magnetic/spintronic biochips, in vitro diagnostics, cell sorting, magnetic nanoparticles, nano-patterning, spin electronic materials and sensors, as well as magnetic integrated inductors and transformers. His research group utilizes modern thin film techniques, lithography, and nanoengineering to devise tailorable materials and devices with novel properties and desirable performances for practical applications. He has over 227 publications, and holds 46 patents (issued and pending), and is an author of the textbook entitled Magnetic Information Storage Technology, and is working on another entitled Biochips and Medical imaging. He was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of the American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors.
Professor, Materials Science and Engineering
Professor, Electrical Engineering
Professor (By courtesy), Radiology - Rad/Molecular Imaging Program at Stanford
Member, Cardiovascular Institute
Member, Child Health Research Institute
Affiliate, Precourt Institute for Energy
Member, Stanford Cancer Institute
Member, Stanford Neurosciences Institute
Affiliate, Stanford Woods Institute for the Environment
Associate Chair, Department of Materials Science and Engineering (2014 - Present)
Honors & Awards
CUSPEA Program, Organized by Nobel Laureate TD Lee (1986)
Inaugural Frederick Terman Faculty Fellow, Stanford University (1994-97)
Partnership Award, IBM (1999)
Distinguished Lecturer, IEEE Magnetics Society (2001)
Obducat Prize, Obducat Prize (2008)
Fellow, The Institute of Electrical and Electronics Engineers (IEEE) (2009)
Thousand Talents Professor (Category B), Tsinghua University, Beijing, China (2011)
Fellow, American Physical Society (APS) (2012)
Faculty Fellow, Stanford Center at Peking University (SCPKU) (2013)
Faculty Award, IBM (2013-4)
Nokia Sensing XCHALLENGE Distinguished Award, XPRIZE Foundation (2014)
PhD, Carnegie Mellon University, Electrical and Computer Engineering (1993)
Community and International Work
Fellow, Center for Innovation in Global Health (CIGH), Asia, Africa, America
Mobile Health, POCT
Opportunities for Student Involvement
Current Research and Scholarly Interests
Dr. Wang is a Professor of Materials Science & Engineering, and jointly a Professor of Electrical Engineering at Stanford University, and by courtesy, a Professor of Radiology at Stanford School of Medicine. He also serves as the Director of Stanford Center for Magnetic Nanotechnology. His research interests lie in nanotechnology and information storage, including magnetic/spintronic biochips, in vitro diagnostics, cell sorting, magnetic nanoparticles, nano-patterning, spin electronic materials and sensors, as well as magnetic integrated inductors and transformers. He has over 200 publications, and holds 43 patents (issued and pending), and is an author of the textbook entitled Magnetic Information Storage Technology. He is a scientific founder of MagArray Inc. and serves on the advisory boards of Nvigen Inc. and several other companies. He was elected a Fellow of the Institute of Electrical and Electronics Engineers (IEEE) and a Fellow of the American Physical Society (APS) for his seminal contributions to magnetic materials and nanosensors. He has been recognized by numerous other honors and awards, including an Inaugural Frederick Terman Fellowship. The international recognition of his work has led to well over 100 invitations to speak or lecture in major conferences and institutions. He received the Ph.D. in Electrical and Computer Engineering from the Carnegie Mellon University in 1993.
- Biochips and Medical Imaging
EE 225, MATSCI 382, SBIO 225 (Win)
- Great Inventions That Matter
MATSCI 83N (Spr)
- New Methods in Thin Film Synthesis
MATSCI 312 (Aut)
Independent Studies (14)
- Directed Investigation
BIOE 392 (Spr, Sum)
- Graduate Independent Study
MATSCI 399 (Aut, Win, Spr, Sum)
- Master's Research
MATSCI 200 (Aut, Win, Spr, Sum)
- Master's Thesis and Thesis Research
EE 300 (Aut, Win, Spr, Sum)
- Participation in Materials Science Teaching
MATSCI 400 (Win, Spr)
- Ph.D. Research
MATSCI 300 (Aut, Win, Spr, Sum)
- Practical Training
MATSCI 299 (Aut, Win, Spr, Sum)
- Special Studies and Reports in Electrical Engineering
EE 191 (Aut, Win, Spr)
- Special Studies and Reports in Electrical Engineering
EE 391 (Aut, Win, Spr, Sum)
- Special Studies and Reports in Electrical Engineering (WIM)
EE 191W (Aut, Win, Spr)
- Special Studies or Projects in Electrical Engineering
EE 190 (Aut, Win, Spr)
- Special Studies or Projects in Electrical Engineering
EE 390 (Aut, Win, Spr, Sum)
- Undergraduate Independent Study
MATSCI 100 (Aut, Win, Spr, Sum)
- Undergraduate Research
MATSCI 150 (Aut, Win, Spr, Sum)
- Directed Investigation
Prior Year Courses
- Biochips and Medical Imaging
EE 225, MATSCI 382, SBIO 225 (Win)
- Magnetic materials in nanotechnology, sensing, and energy
MATSCI 347 (Spr)
- New Methods in Thin Film Synthesis
MATSCI 312 (Aut)
- Biochips and Medical Imaging
EE 225, MATSCI 382, SBIO 225 (Win)
- New Methods in Thin Film Synthesis
MATSCI 312 (Aut)
- Bio-chips, Imaging and Nanomedicine
EE 225, MATSCI 382, SBIO 225 (Win)
- China Technology and Engineering
OSPGEN 38 (Sum)
- Introduction to Magnetism and Magnetic Nanostructures
MATSCI 347 (Spr)
- New Methods in Thin Film Synthesis
MATSCI 312 (Aut)
- Biochips and Medical Imaging
Graduate and Fellowship Programs
Molecular profiling of single circulating tumor cells from lung cancer patients
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (52): E8379-E8386
Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.
View details for DOI 10.1073/pnas.1608461113
View details for Web of Science ID 000391090800003
View details for PubMedID 27956614
View details for PubMedCentralID PMC5206556
High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays
2016; 10 (12): 10652-10660
Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid. We have also developed a chemical regeneration scheme to perform multiplex assays with a high level of reproducibility, resulting in greatly reduced experimental costs. In addition, we show that peptides synthesized directly on the nanosensors are approximately two times more sensitive than directly spotted peptides. Reusable peptide nanosensor microarrays enable precise detection of autoantibodies with high resolution and sensitivity and show promise for investigating antibody-mediated immune responses to autoantigens, vaccines, and pathogen-derived antigens as well as other fundamental peptide-protein interactions.
View details for DOI 10.1021/acsnano.6b03786
View details for Web of Science ID 000391079700007
View details for PubMedID 27636738
Portable, one-step, and rapid GMR biosensor platform with smartphone interface.
Biosensors & bioelectronics
2016; 85: 1-7
Quantitative immunoassay tests in clinical laboratories require trained technicians, take hours to complete with multiple steps, and the instruments used are generally immobile-patient samples have to be sent in to the labs for analysis. This prevents quantitative immunoassay tests to be performed outside laboratory settings. A portable, quantitative immunoassay device will be valuable in rural and resource-limited areas, where access to healthcare is scarce or far away. We have invented Eigen Diagnosis Platform (EDP), a portable quantitative immunoassay platform based on Giant Magnetoresistance (GMR) biosensor technology. The platform does not require a trained technician to operate, and only requires one-step user involvement. It displays quantitative results in less than 15min after sample insertion, and each test costs less than US$4. The GMR biosensor employed in EDP is capable of detecting multiple biomarkers in one test, enabling a wide array of immune diagnostics to be performed simultaneously. In this paper, we describe the design of EDP, and demonstrate its capability. Multiplexed assay of human immunoglobulin G and M (IgG and IgM) antibodies with EDP achieves sensitivities down to 0.07 and 0.33 nanomolar, respectively. The platform will allow lab testing to be performed in remote areas, and open up applications of immunoassay testing in other non-clinical settings, such as home, school, and office.
View details for DOI 10.1016/j.bios.2016.04.046
View details for PubMedID 27148826
Small Molecule Detection in Saliva Facilitates Portable Tests of Marijuana Abuse.
2016; 88 (15): 7457-7461
As medical and recreational use of cannabis, or marijuana, becomes more prevalent, law enforcement needs a tool to evaluate whether drivers are operating vehicles under the influence of cannabis, specifically the psychoactive substance, tetrahydrocannabinol (THC). However, the cutoff concentration of THC that causes impairment is still controversial, and current on-site screening tools are not sensitive enough to detect trace amounts of THC in oral fluids. Here we present a novel sensing platform that employs giant magnetoresistive (GMR) biosensors integrated with a portable reader system and smartphone to detect THC in saliva using competitive assays. With a simple saliva collection scheme, we have optimized the assay to measure THC in the range from 0 to 50 ng/mL, covering most cutoff values proposed in previous studies. This work facilitates on-site screening for THC and shows potential for testing of other small molecule drugs and analytes in point-of-care (POC) settings.
View details for DOI 10.1021/acs.analchem.6b01688
View details for PubMedID 27434697
- Effect of Mg Oxidation Degree on Rashba-Effect-Induced Torques in Ta/CoFeB/Mg(MgO) Multilayer IEEE TRANSACTIONS ON MAGNETICS 2016; 52 (7)
- Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection BIOSENSORS & BIOELECTRONICS 2016; 80: 359-365
Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.
View details for DOI 10.1038/srep27623
View details for Web of Science ID 000377358700002
View details for PubMedID 27279139
- Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors SCIENTIFIC REPORTS 2016; 6
Magneto-nanosensor platform for probing low-affinity protein-protein interactions and identification of a low-affinity PD-L1/PD-L2 interaction.
2016; 7: 12220-?
Substantial efforts have been made to understand the interactions between immune checkpoint receptors and their ligands targeted in immunotherapies against cancer. To carefully characterize the complete network of interactions involved and the binding affinities between their extracellular domains, an improved kinetic assay is needed to overcome limitations with surface plasmon resonance (SPR). Here, we present a magneto-nanosensor platform integrated with a microfluidic chip that allows measurement of dissociation constants in the micromolar-range. High-density conjugation of magnetic nanoparticles with prey proteins allows multivalent receptor interactions with sensor-immobilized bait proteins, more closely mimicking natural-receptor clustering on cells. The platform has advantages over traditional SPR in terms of insensitivity of signal responses to pH and salinity, less consumption of proteins and better sensitivities. Using this platform, we characterized the binding affinities of the PD-1-PD-L1/PD-L2 co-inhibitory receptor system, and discovered an unexpected interaction between the two known PD-1 ligands, PD-L1 and PD-L2.
View details for DOI 10.1038/ncomms12220
View details for PubMedID 27447090
View details for PubMedCentralID PMC4961847
Bio-Inspired Stretchable Absolute Pressure Sensor Network.
2016; 16 (1)
A bio-inspired absolute pressure sensor network has been developed. Absolute pressure sensors, distributed on multiple silicon islands, are connected as a network by stretchable polyimide wires. This sensor network, made on a 4'' wafer, has 77 nodes and can be mounted on various curved surfaces to cover an area up to 0.64 m × 0.64 m, which is 100 times larger than its original size. Due to Micro Electro-Mechanical system (MEMS) surface micromachining technology, ultrathin sensing nodes can be realized with thicknesses of less than 100 µm. Additionally, good linearity and high sensitivity (~14 mV/V/bar) have been achieved. Since the MEMS sensor process has also been well integrated with a flexible polymer substrate process, the entire sensor network can be fabricated in a time-efficient and cost-effective manner. Moreover, an accurate pressure contour can be obtained from the sensor network. Therefore, this absolute pressure sensor network holds significant promise for smart vehicle applications, especially for unmanned aerial vehicles.
View details for DOI 10.3390/s16010055
View details for PubMedID 26729134
Microfluidic multiplexed partitioning enables flexible and effective utilization of magnetic sensor arrays.
Lab on a chip
2015; 15 (22): 4273-4276
We demonstrate microfluidic partitioning of a giant magnetoresistive sensor array into individually addressable compartments that enhances its effective use. Using different samples and reagents in each compartment enables measuring of cross-reactive species and wide dynamic ranges on a single chip. This compartmentalization technique motivates the employment of high density sensor arrays for highly parallelized measurements in lab-on-a-chip devices.
View details for DOI 10.1039/c5lc00953g
View details for PubMedID 26395039
- Achieving Isotropic Permeability for Integrated Inductors IEEE TRANSACTIONS ON MAGNETICS 2015; 51 (11)
- 45 degrees Induced Magnetic Anisotropy for Isotropic High-Frequency Permeability IEEE TRANSACTIONS ON MAGNETICS 2015; 51 (11)
- Electric Field Sensor Based on Piezoelectric Bending Effect for Wide Range Measurement IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS 2015; 62 (9): 5730-5737
High performance wash-free magnetic bioassays through microfluidically enhanced particle specificity.
2015; 5: 11693-?
Magnetic biosensors have emerged as a sensitive and versatile platform for high performance medical diagnostics. These magnetic biosensors require well-tailored magnetic particles as detection probes, which need to give rise to a large and specific biological signal while showing very low nonspecific binding. This is especially important in wash-free bioassay protocols, which do not require removal of particles before measurement, often a necessity in point of care diagnostics. Here we show that magnetic interactions between magnetic particles and magnetized sensors dramatically impact particle transport and magnetic adhesion to the sensor surfaces. We investigate the dynamics of magnetic particles' biomolecular binding and magnetic adhesion to the sensor surface using microfluidic experiments. We elucidate how flow forces can inhibit magnetic adhesion, greatly diminishing or even eliminating nonspecific signals in wash-free magnetic bioassays, and enhancing signal to noise ratios by several orders of magnitude. Our method is useful for selecting and optimizing magnetic particles for a wide range of magnetic sensor platforms.
View details for DOI 10.1038/srep11693
View details for PubMedID 26123868
- Microfluidic multiplexed partitioning enables flexible and effective utilization of magnetic sensor arrays LAB ON A CHIP 2015; 15 (22): 4273-4276
- Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips LAB ON A CHIP 2014; 14 (1): 78-88
Wafer-Scale Synthesis of Monodisperse Synthetic Magnetic Multilayer Nanorods
2014; 14 (1): 333-338
A double exposure technique has been used to fabricate nanoimprint stamps for making monodisperse nanorods with controllable lengths. The nanorod length is defined by a normal photolithography projection process whereas the nanorod width is defined by an edge-lithography process using a soft polydimethylsiloxane (PDMS) contact mask. Taking advantage of edge-lithography, the nanorod width can be less than the diffraction limit of the exposure light. Using these nanorod stamps, synthetic magnetic multilayer (SMM) nanorods have been fabricated using nanoimprint lithography, resulting in a length variation of ∼3%. Nanorod magnetic properties have been characterized in both longitudinal and in-plane transverse directions of the nanorods. A theoretical model has been established to explain the magnetic responses and has revealed that both shape anisotropy and interlayer interactions are important in determining the properties of SMM nanorods.
View details for DOI 10.1021/nl404089t
View details for Web of Science ID 000329586700053
View details for PubMedID 24329003
- Functionalization of high-moment magnetic nanodisks for cell manipulation and separation NANO RESEARCH 2013; 6 (10): 745-751
Modeling and experiments of magneto-nanosensors for diagnostics of radiation exposure and cancer.
2013; 15 (4): 665-671
We present a resistive network model, protein assay data, and outlook of the giant magnetoresistive (GMR) spin-valve magneto-nanosensor platform ideal for multiplexed detection of protein biomarkers in solutions. The magneto-nanosensors are designed to have optimal performance considering several factors such as sensor dimension, shape anisotropy, and magnetic nanoparticle tags. The resistive network model indicates that thinner spin-valve sensors with narrower width lead to higher signals from magnetic nanoparticle tags. Standard curves and real-time measurements showed a sensitivity of ~10 pM for phosphorylated-structural maintenance of chromosome 1 (phosphor-SMC1), ~53 fM for granulocyte colony stimulation factor (GCSF), and ~460 fM for interleukin-6 (IL6), which are among the representative biomarkers for radiation exposure and cancer.
View details for DOI 10.1007/s10544-012-9678-z
View details for PubMedID 22763391
View details for PubMedCentralID PMC3674217
- Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation SCIENTIFIC REPORTS 2013; 3
- Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation IEEE TRANSACTIONS ON MAGNETICS 2013; 49 (7): 3434-3437
- Kerr-Imaged Edge-Curling Wall Effects of Narrow Magnetic Cores IEEE TRANSACTIONS ON MAGNETICS 2013; 49 (7): 4017-4020
- Integrated Transformers With Sputtered Laminated Magnetic Core IEEE TRANSACTIONS ON MAGNETICS 2013; 49 (7): 4021-4027
- A 256 Pixel Magnetoresistive Biosensor Microarray in 0.18 mu m CMOS IEEE Radio Frequency Integrated Circuits (RFIC) Symposium in Conjunction with the IEEE MTT-S International Microwave Symposium (IMS) / Microwave Week IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2013: 1290–1301
Emerging protein array technologies for proteomics
EXPERT REVIEW OF PROTEOMICS
2013; 10 (1): 65-75
Numerous efforts have been made to understand fundamental biology of diseases based on gene expression. However, the relationship between gene expression and onset of disease often remains obscure. The great advances in protein microarrays allow us to investigate this unclear question through protein profiles, which are regarded as more reliable than gene expressions to serve as the harbinger of disease onset or as the biomarker of disease treatment monitoring. The authors review two relatively new platforms of protein arrays, along with an introduction to the common basis of protein array technologies. Immobilization of proteins on the surface of arrays and neutralizing reactive areas after the immobilization are key practical issues in the field of protein array. One of the emerging protein array technologies is the magneto-nanosensor array, where giant magnetoresistive sensors are used to quantitatively measure the analytes of interest, which are labeled with magnetic nanoparticles. Similar to giant magnetoresistive sensors, several different ways of utilizing magnetic properties for biomolecular detection have been developed and are reviewed here. Another emerging protein array technology is nucleic acid programmable protein arrays, which have thousands of protein features directly expressed by nucleic acids on the array surface. The authors anticipate that these two emerging protein array platforms can be combined to produce synergistic benefits and open new applications in proteomics and clinical diagnostics.
View details for DOI 10.1586/EPR.12.67
View details for Web of Science ID 000315163000015
View details for PubMedID 23414360
View details for PubMedCentralID PMC4143142
Nanosensor dosimetry of mouse blood proteins after exposure to ionizing radiation.
2013; 3: 2234-?
Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring protein concentrations in blood for medical diagnosis. Using an in vivo mouse radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at ≥ 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A multiplex assay with both proteins showed improved dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose and time responses, low-dose sensitivity, small volume requirements, and rapid speed that have important advantages in radiation triage biodosimetry.
View details for DOI 10.1038/srep02234
View details for PubMedID 23868657
View details for PubMedCentralID PMC3715761
Effect of Magnetic Field Gradient on Effectiveness of the Magnetic Sifter for Cell Purification
IEEE TRANSACTIONS ON MAGNETICS
2013; 49 (1): 316-320
In our experiments with NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen, we demonstrate capture efficiencies above 90% even at sample flow rates of 5 ml/h through our microfabricated magnetic sifter. We also improve the elution efficiencies from between 50% and 60% to close to 90% via optimization of the permanent magnet size and position used to magnetize the sifter. We then explain our observations via the use of finite element software for magnetic field and field gradient distributions, and a particle tracing algorithm, illustrating the impact of magnetic field gradients on the performance of the magnetic sifter. The high capture and elution efficiencies observed here is especially significant for magnetic separation of biologically interesting but rare moieties such as cancer stem cells for downstream analysis.
View details for DOI 10.1109/TMAG.2012.2224851
View details for Web of Science ID 000312831500027
Magnetically ultraresponsive nanoscavengers for next-generation water purification systems.
2013; 4: 1866-?
The development of sustainable, robust and energy efficient water purification technology is still challenging. Although use of nanoparticles is promising, methods are needed for their efficient recovery post treatment. Here we address this issue by fabrication of magnetically ultraresponsive 'nanoscavengers', nanoparticles containing synthetic antiferromagnetic core layers and functional capping layers. When dispersed in water, the nanoscavengers efficiently interact with contaminants to remove them from the water. They are then quickly collected (<5 min) with a permanent magnet, owing to their magnetically ultraresponsive core layers. Specifically, we demonstrate fabrication and deployment of Ag-capped nanoscavengers for disinfection followed by application of an external magnetic field for separation. We also develop and validate a collision-based model for pathogen inactivation, and propose a cyclical water purification scheme in which nanoscavengers are recovered and recycled for contaminant removal.
View details for DOI 10.1038/ncomms2892
View details for PubMedID 23673651
Raman-Active Two-Tiered Ag Nanoparticles with a Concentric Cavity
2011; 7 (23): 3276-3280
A two-tiered Ag nanoparticle containing a cavity at the center of each nanoparticle is generated by two simple steps of nano-imprinting and metal vacuum deposition. It enables sub-zeptomole detection of organic molecules and five orders of the dynamic sensing range.
View details for DOI 10.1002/smll.201101523
View details for Web of Science ID 000298288100004
View details for PubMedID 21990231
Sombrero-Shaped Plasmonic Nanoparticles with Molecular-Level Sensitivity and Multifunctionality
2011; 5 (8): 6449-6457
We demonstrate top-down synthesis of monodisperse plasmonic nanoparticles designed to contain internal Raman hot spots. Our Raman-active nanoparticles are fabricated using nanoimprint lithography and thin-film deposition and are composed of novel internal structures with sublithographic dimensions: a disk-shaped Ag core, a Petri-dish-shaped SiO(2) base whose inner surface is coated with Ag film, and a sub-10 nm scale circular gap between the core and the base. Confocal Raman measurements and electromagnetic simulations show that Raman hot spots appear at the inside perimeter of individual nanoparticles and serve as the source of a 1000-fold improvement of minimum molecular detection level that enables detection of signals from a few molecules near hot spots. A multimodality version of these nanoparticles, which includes the functionality offered by magnetic multilayers, is also demonstrated. These results illustrate the potential of direct fabrication for creating exotic monodisperse nanoparticles, which combine engineered internal nanostructures and multilayer composite materials, for use in nanoparticle-based molecular imaging and detection.
View details for DOI 10.1021/nn201649n
View details for Web of Science ID 000294085400044
View details for PubMedID 21732686
Autoassembly Protein Arrays for Analyzing Antibody Cross-Reactivity
2011; 11 (7): 2579-2583
We report an autoassembly protein array capable of rapidly screening for aberrant antibody-antigen binding events. Our technique combines magnetic nanoparticle technology with proximity-based, magnetically responsive nanosensors for rapid (under 15 min) and high-density screening of antibody cross-reactivity at sensitivities down to 50 fM in a homogeneous assay. This method will enable the identification of the precise cause of aberrant or cross-reactive binding events in an easy-to-use, rapid, and high-throughput manner.
View details for DOI 10.1021/nl1026056
View details for Web of Science ID 000292849400001
View details for PubMedID 20804215
Fabrication of planar, layered nanoparticles using tri-layer resist templates
2011; 22 (18)
A simple and universal pathway to produce free multilayer synthetic nanoparticles is developed based on lithography, vapor phase deposition and a tri-layer resist lift-off and release process. The fabrication method presented in this work is ideal for production of a broad range of nanoparticles, either free in solution or still attached to an intact release layer, with unique magnetic, optical, radioactive, electronic and catalytic properties. Multi-modal capabilities are implicit in the layered architecture. As an example, directly fabricated magnetic nanoparticles are evaluated to illustrate the structural integrity of thin internal multilayers and the nanoparticle stability in aggressive biological environments, which is highly desired for biomedical applications.
View details for DOI 10.1088/0957-4484/22/18/185302
View details for Web of Science ID 000288653300005
View details for PubMedID 21415483
Quantification of protein interactions and solution transport using high-density GMR sensor arrays
2011; 6 (5): 314-320
Monitoring the kinetics of protein interactions on a high-density sensor array is vital to drug development and proteomic analysis. Label-free kinetic assays based on surface plasmon resonance are the current gold standard, but they have poor detection limits, suffer from non-specific binding, and are not amenable to high-throughput analyses. Here, we show that magnetically responsive nanosensors that have been scaled to over 100,000 sensors per cm² can be used to measure the binding kinetics of various proteins with high spatial and temporal resolution. We present an analytical model that describes the binding of magnetically labelled antibodies to proteins that are immobilized on the sensor surface. This model is able to quantify the kinetics of antibody-antigen binding at sensitivities as low as 20 zeptomoles of solute.
View details for DOI 10.1038/NNANO.2011.45
View details for Web of Science ID 000290301300013
View details for PubMedID 21478869
nanoLAB: An ultraportable, handheld diagnostic laboratory for global health
LAB ON A CHIP
2011; 11 (5): 950-956
Driven by scientific progress and economic stimulus, medical diagnostics will move to a stage in which straightforward medical diagnoses are independent of physician visits and large centralized laboratories. The future of basic diagnostic medicine will lie in the hands of private individuals. We have taken significant strides towards achieving this goal by developing an autoassembly assay for disease biomarker detection which obviates the need for washing steps and is run on a handheld sensing platform. By coupling magnetic nanotechnology with an array of magnetically responsive nanosensors, we demonstrate a rapid, multiplex immunoassay that eliminates the need for trained technicians to run molecular diagnostic tests. Furthermore, the platform is battery-powered and ultraportable, allowing the assay to be run anywhere in the world by any individual.
View details for DOI 10.1039/c0lc00534g
View details for Web of Science ID 000287409600024
View details for PubMedID 21264375
Effects of Ionizing Radiation on Self-Renewal and Pluripotency of Human Embryonic Stem Cells
2010; 70 (13): 5539-5548
Human embryonic stem cells (hESC) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs, nor has any study assessed their ability to form teratomas, the definitive test of pluripotency. In this study, we use microarrays to analyze the global gene expression changes in hESCs after low-dose (0.4 Gy), medium-dose (2 Gy), and high-dose (4 Gy) irradiation. We identify genes and pathways at each radiation dose that are involved in cell death, p53 signaling, cell cycling, cancer, embryonic and organ development, and others. Using Gene Set Enrichment Analysis, we also show that the expression of a comprehensive set of core embryonic transcription factors is not altered by radiation at any dose. Transplantation of irradiated hESCs to immune-deficient mice results in teratoma formation from hESCs irradiated at all doses, definitive proof of pluripotency. Further, using a bioluminescence imaging technique, we have found that irradiation causes hESCs to initially die after transplantation, but the surviving cells quickly recover by 2 weeks to levels similar to control. To conclude, we show that similar to somatic cells, irradiated hESCs suffer significant death and apoptosis after irradiation. However, they continue to remain pluripotent and are able to form all three embryonic germ layers. Studies such as this will help define the limits for radiation exposure for pregnant women and also radiotracer reporter probes for tracking cellular regenerative therapies.
View details for DOI 10.1158/0008-5472.CAN-09-4238
View details for Web of Science ID 000279396800036
View details for PubMedID 20530673
View details for PubMedCentralID PMC3014320
GMR biosensor arrays: Correction techniques for reproducibility and enhanced sensitivity
BIOSENSORS & BIOELECTRONICS
2010; 25 (9): 2177-2181
Giant magnetoresistive biosensors possess great potential in biomedical applications for quantitatively detecting magnetically tagged biomolecules. Magnetic sensing does not suffer from the high background levels found in optical sensing modalities such as the enzyme linked immunosorbent assay translating into a technology with higher sensitivity. However, to reveal the full potential of these sensors and compensate for non-idealities such as temperature dependence, digital correction and calibration techniques are not only useful but imperative. Using these calibration techniques to correct for process variations and dynamic changes in the sensing environment (such as temperature and magnetic field), we are able to obtain extremely sensitive and, more importantly, reproducible results for quantifiable biomolecular reorganization. The reproducibility of the system was improved by over 3 x using digital correction techniques and the sensors are made temperature independent by using a novel background correction technique.
View details for DOI 10.1016/j.bios.2010.01.039
View details for Web of Science ID 000277930000029
View details for PubMedID 20219342
GMR biosensor arrays: A system perspective
BIOSENSORS & BIOELECTRONICS
2010; 25 (9): 2051-2057
Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time.
View details for DOI 10.1016/j.bios.2010.01.038
View details for Web of Science ID 000277930000009
View details for PubMedID 20207130
Portable Biomarker Detection with Magnetic Nanotags
International Symposium on Circuits and Systems Nano-Bio Circuit Fabrics and Systems (ISCAS 2010)
IEEE. 2010: 1779–1782
View details for Web of Science ID 000287216002001
Matrix-insensitive protein assays push the limits of biosensors in medicine
2009; 15 (11): 1327-U130
Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.
View details for DOI 10.1038/nm.2032
View details for Web of Science ID 000271543700023
View details for PubMedID 19820717
Microfabricated magnetic sifter for high-throughput and high-gradient magnetic separation
7th International Conference on Scientific and Clinical Applications of Magnetic Carriers
ELSEVIER SCIENCE BV. 2009: 1436–39
A microfabricated magnetic sifter has been designed and fabricated for applications in biological sample preparation. The device enables high-throughput, high-gradient magnetic separation of magnetic nanoparticles by utilizing columnar fluid flow through a dense array (~5000/mm(2)) of micropatterned slots in a magnetically soft membrane. The potential of the sifter for separation of magnetic nanoparticles conjugated with capture antibodies is demonstrated through quantitative separation experiments with CD138-labelled MACS nanoparticles. Capture efficiencies ranging from 28-37% and elution efficiencies greater than 73% were measured for a single pass through the sifter.
View details for DOI 10.1016/j.jmmm.2009.02.062
View details for Web of Science ID 000265278000025
Protein-Functionalized Synthetic Antiferromagnetic Nanoparticles for Biomolecule Detection and Magnetic Manipulation
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2009; 48 (9): 1620-1624
Direct protein functionalization provides synthetic antiferromagnetic nanoparticles with high chemical specificity and multifunctionality. These nanoparticle-protein conjugates function as improved magnetic labels for biological detection experiments, and exhibit tunable responses to a small external magnetic field gradient, thus allowing the observation of distinctive single nanoparticle motion.
View details for DOI 10.1002/anie.200803994
View details for Web of Science ID 000263642300018
View details for PubMedID 19156803
Multiplex protein assays based on real-time magnetic nanotag sensing
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (52): 20637-20640
Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.
View details for DOI 10.1073/pnas.0810822105
View details for Web of Science ID 000262092800015
View details for PubMedID 19074273
Giant magnetoresistive biochip for DNA detection and HPV genotyping
BIOSENSORS & BIOELECTRONICS
2008; 24 (1): 99-103
A giant magnetoresistive (GMR) biochip based on spin valve sensor array and magnetic nanoparticle labels was developed for inexpensive, sensitive and reliable DNA detection. The DNA targets detected in this experiment were PCR products amplified from Human Papillomavirus (HPV) plasmids. The concentrations of the target DNA after PCR were around 10 nM in most cases, but concentrations of 10 pM were also detectable, which is demonstrated by experiments with synthetic DNA samples. A mild but highly specific surface chemistry was used for probe oligonucleotide immobilization. Double modulation technique was used for signal detection in order to reduce the 1/f noise in the sensor. Twelve assays were performed with an accuracy of approximately 90%. Magnetic signals were consistent with particle coverage data measured with Scanning Electron Microscopy (SEM). More recent research on microfluidics showed the potential of reducing the assay time below one hour. This is the first demonstration of magnetic DNA detection using plasmid-derived samples. This study provides a direct proof that GMR sensors can be used for biomedical applications.
View details for DOI 10.1016/j.bios.2008.03.030
View details for Web of Science ID 000259425300015
View details for PubMedID 18457945
- Giant Magnetoresistive Biosensors for Molecular Diagnosis: Surface Chemistry and Assay Development Conference on Biosensing SPIE-INT SOC OPTICAL ENGINEERING. 2008
- Spin filter based tunnel junctions JOURNAL OF APPLIED PHYSICS 2006; 100 (12)
- A novel zero-drift detection method for highly sensitive GMR biochips 41st IEEE International Magnetics Conference (Intermag 2006) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2006: 3560–62
- Permeability of fine magnetic particles: Measurements, calibration, and pitfalls 41st IEEE International Magnetics Conference (Intermag 2006) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2006: 3335–37
Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects
2006; 6 (4): 669-676
We report the in vivo targeting and imaging of tumor vasculature using arginine-glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD intravenously. The tumor fluorescence intensity reached maximum at 6 h postinjection with good contrast. The results reported here open up new perspectives for integrin-targeted near-infrared optical imaging and may aid in cancer detection and management including imaging-guided surgery.
View details for DOI 10.1021/nl052405t
View details for Web of Science ID 000236916200015
View details for PubMedID 16608262
Spin valve sensors for ultrasensitive detection of superparamagnetic nanoparticles for biological applications
SENSORS AND ACTUATORS A-PHYSICAL
2006; 126 (1): 98-106
We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparamagnetic nanoparticles as potential biomolecular labels in magnetic biodetection technology. We discuss the sensor design and experimentally demonstrate that as few as approximately 23 monodisperse 16-nm superparamagnetic Fe(3)O(4) nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in detection. A patterned self-assembly method of nanoparticles, based on a polymer-mediated process and fine lithography, is developed for the detection. It is found that sensor signal increases linearly with the number of nanoparticles.
View details for DOI 10.1016/j.sna.2005.10.001
View details for Web of Science ID 000235103900015
Microstructures of FeTaN films in the neck region of magnetic recording heads
8th Joint Magnetism and Magnetic Materials International Magnetics Conference (MMM-INTERMAG)
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2001: 3039–42
View details for Web of Science ID 000170911100014
- Properties of a new soft magnetic material Nature 2000; 407 (6801): 150–51
Magnetic properties and high-frequency responses of high moment FeTaN/AlN laminates for high-data-rate magnetic recording
IEEE TRANSACTIONS ON MAGNETICS
1999; 35 (5): 2502-2504
View details for Web of Science ID 000083151100092
Epitaxial growth of atomically flat spin dependent tunneling junctions
Symposium on Epitaxial Growth-Principles and Applications
MATERIALS RESEARCH SOCIETY. 1999: 73–78
View details for Web of Science ID 000082591100010
Study of natural oxidation of ultra-thin aluminum layers with in-situ resistance measurement
Symposium U on In Situ Process Diagnostics and Modelling, at the 1999 MRS Spring Meeting
MATERIALS RESEARCH SOCIETY. 1999: 185–190
View details for Web of Science ID 000082591000026
Microstructures and properties of high saturation soft magnetic materials for advanced recording reads
Symposium L on Materials for High-Density Magnetic Recording / Symposium M on Integrated Magneto-Optics at the MRS Spring Meeting
MATERIALS RESEARCH SOCIETY. 1998: 5–5
View details for Web of Science ID 000076893400001
- High-Density 2D Homo- and Hetero- Plasmonic Dimers with Universal Sub-10-nm Gaps ACS NANO 2015; 9 (9): 9331-9339
- A Nonintrusive Power Supply Design for Self-Powered Sensor Networks in the Smart Grid by Scavenging Energy From AC Power Line IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS 2015; 62 (7): 4398-4407
- Increasing ferromagnetic resonance frequency using lamination and shape JOURNAL OF APPLIED PHYSICS 2015; 117 (17)
- Hysteretic Modeling of Output Characteristics of Giant Magnetoresistive Current Sensors IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS 2015; 62 (1): 516-524
- Spin-wave resonances in the presence of a Bloch wall PHYSICAL REVIEW B 2014; 89 (22)
Genetically encoded multispectral labeling of proteins with polyfluorophores on a DNA backbone.
Journal of the American Chemical Society
2013; 135 (16): 6184-6191
Genetically encoded methods for protein conjugation are of high importance as biological tools. Here we describe the development of a new class of dyes for genetically encoded tagging that add new capabilities for protein reporting and detection via HaloTag methodology. Oligodeoxyfluorosides (ODFs) are short DNA-like oligomers in which the natural nucleic acid bases are replaced by interacting fluorescent chromophores, yielding a broad range of emission colors using a single excitation wavelength. We describe the development of an alkyl halide dehalogenase-compatible chloroalkane linker phosphoramidite derivative that enables the rapid automated synthesis of many possible dyes for protein conjugation. Experiments to test the enzymatic self-conjugation of nine different DNA-like dyes to proteins with HaloTag domains in vitro were performed, and the data confirmed the rapid and efficient covalent labeling of the proteins. Notably, a number of the ODF dyes were found to increase in brightness or change color upon protein conjugation. Tests in mammalian cellular settings revealed that the dyes are functional in multiple cellular contexts, both on the cell surface and within the cytoplasm, allowing protein localization to be imaged in live cells by epifluorescence and laser confocal microscopy.
View details for DOI 10.1021/ja4004393
View details for PubMedID 23590213
Glaucoma and vitamins A, C, and E supplement intake and serum levels in a population-based sample of the United States
2013; 27 (4): 487-494
To investigate the potential association between glaucoma prevalence and supplemental intake, as well as serum levels of vitamins A, C and E.This cross-sectional study included 2912 participants in the 2005-2006 National Health and Nutrition Examination Survey, age ≥40 years, who self-reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements during the preceding 30-day period. Participants also underwent serum measurements of vitamins A, C, and E (both alpha- and gamma-tocopherol). Information on the primary outcome measure, presence or absence of glaucoma, as well as demographic information, comorbidities and health-related behaviors, was assessed via interview.Multivariate odds ratios for self-reported glaucoma, comparing the highest quartile of consumption to no consumption, and adjusted for potential confounding variables were 0.48 (95% confidence interval (CI) 0.13-1.82) for vitamin A, 0.47 (95% CI 0.23-0.97) for vitamin C, and 2.59 (95% CI 0.89-7.56) for vitamin E. Adjusted odds ratios for self-reported glaucoma comparing the highest vs lowest quintiles of vitamin serum levels were 1.44 (95% CI 0.79-2.62) for vitamin A, 0.94 (95% CI 0.42-2.11) for vitamin C, 1.40 (95% CI 0.70-2.81) for alpha-tocopherol, and 0.64 (95% CI 0.24-1.70) for gamma-tocopherol.Neither supplementary consumption with nor serum levels of vitamins A and E were found to be associated with glaucoma prevalence. While low- and high-dose supplementary consumption of vitamin C was found to be associated with decreased odds of glaucoma, serum levels of vitamin C did not correlate with glaucoma prevalence.
View details for DOI 10.1038/eye.2013.10
View details for Web of Science ID 000317594000005
View details for PubMedID 23429409
A SHIFT IN THE LONG-TERM MODE OF FORAMINIFERAN SIZE EVOLUTION CAUSED BY THE END-PERMIAN MASS EXTINCTION
2013; 67 (3): 816-827
Size is among the most important traits of any organism, yet the factors that control its evolution remain poorly understood. In this study, we investigate controls on the evolution of organismal size using a newly compiled database of nearly 25,000 foraminiferan species and subspecies spanning the past 400 million years. We find a transition in the pattern of foraminiferan size evolution from correlation with atmospheric pO2 during the Paleozoic (400-250 million years ago) to long-term stasis during the post-Paleozoic (250 million years ago to present). Thus, a dramatic shift in the evolutionary mode coincides with the most severe biotic catastrophe of the Phanerozoic (543 million years ago to present). Paleozoic tracking of pO2 was confined to Order Fusulinida, whereas Paleozoic lagenides, miliolids, and textulariids were best described by the stasis model. Stasis continued to best describe miliolids and textulariids during post-Paleozoic time, whereas random walk was the best supported mode for the other diverse orders. The shift in evolutionary dynamics thus appears to have resulted primarily from the selective elimination of fusulinids at the end of the Permian Period. These findings illustrate the potential for mass extinction to alter macroevolutionary dynamics for hundreds of millions of years.
View details for DOI 10.1111/j.1558-5646.2012.01807.x
View details for Web of Science ID 000315894800018
View details for PubMedID 23461330
Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging
JOURNAL OF NEURO-ONCOLOGY
2013; 112 (1): 9-15
We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.
View details for DOI 10.1007/s11060-012-1031-0
View details for Web of Science ID 000315487900002
View details for PubMedID 23334608
Incidence of Non-Small-Cell Lung Cancer among California Hispanics According to Neighborhood Socioeconomic Status
JOURNAL OF THORACIC ONCOLOGY
2013; 8 (3): 287-294
Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and ever-smoking rates among California Hispanics according to measures of SES.We computed neighborhood (n)SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation.Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men.For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES.
View details for DOI 10.1097/JTO.0b013e31827bd7f5
View details for Web of Science ID 000316205600012
View details for PubMedID 23399956
FCHSD1 and FCHSD2 Are Expressed in Hair Cell Stereocilia and Cuticular Plate and Regulate Actin Polymerization In Vitro
2013; 8 (2)
Mammalian FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. We report here that FCHSD1 and FCHSD2 are expressed in mouse cochlear sensory hair cells. FCHSD1 mainly localizes to the cuticular plate, whereas FCHSD2 mainly localizes along the stereocilia in a punctuate pattern. Nervous Wreck (Nwk), the Drosophila ortholog of FCHSD1 and FCHSD2, has been shown to bind Wsp and play an important role in F-actin assembly. We show that, like its Drosophila counterpart, FCHSD2 interacts with WASP and N-WASP, the mammalian orthologs of Drosophila Wsp, and stimulates F-actin assembly in vitro. In contrast, FCHSD1 doesn't bind WASP or N-WASP, and can't stimulate F-actin assembly when tested in vitro. We found, however, that FCHSD1 binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9 (SNX9), a well characterized BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization. FCHSD1 greatly enhances SNX9's WASP-Arp2/3-dependent F-actin polymerization activity. In hair cells, SNX9 was detected in the cuticular plate, where it colocalizes with FCHSD1. Our results suggest that FCHSD1 and FCHSD2 could modulate F-actin assembly or maintenance in hair cell stereocilia and cuticular plate.
View details for DOI 10.1371/journal.pone.0056516
View details for Web of Science ID 000315184200089
View details for PubMedID 23437151
- Pressure-induced symmetry breaking in tetragonal CsAuI3 PHYSICAL REVIEW B 2013; 87 (5)
Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival in Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2); a Bone Marrow Pathology Group Study
102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP)
NATURE PUBLISHING GROUP. 2013: 358A–358A
View details for Web of Science ID 000314789302115
The Pathologist's Approach to T-Cell Large Granular Lymphocytic Leukemia Diagnosis: A Multicenter Comparative Study by the Bone Marrow Pathology Group
102nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP)
NATURE PUBLISHING GROUP. 2013: 351A–351A
View details for Web of Science ID 000314789302087
- Gene Ontology Annotations and Resources NUCLEIC ACIDS RESEARCH 2013; 41 (D1): D530-D535
Association between Myopia and Glaucoma in the United States Population
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2013; 54 (1): 830-835
To investigate the association between myopia and the prevalence of glaucoma.This cross-sectional study included 5277 participants from the 2005 to 2008 National Health and Nutrition Examination Survey, greater than or equal to 40 years old, without history of cataract or refractive surgery, who underwent auto-refraction measurement. The predictor was refractive status; emmetropia (-0.99 to +0.99 diopters [D]), mild myopia (-1.00 to -2.99 D), moderate myopia (-3.00 to -5.99 D), severe myopia (> -6.00 D), and hyperopia (> 1.00 D). The outcomes were self-reported glaucoma, vertical cup-to-disc ratio and visual field defects as found on frequency doubling technology (FDT) testingOdds of self-reported glaucoma were not significantly increased in mild (odds ratio [OR] 0.90, confidence interval [CI] 0.56-1.45), moderate (OR 1.40, CI 0.62-3.16), or severe (OR 0.26, CI 0.08-0.80) myopes compared with emmetropes. Odds of vertical cup-to-disc ratio greater than or equal to 0.7 were not significantly increased in mild (OR 0.84, CI 0.31-2.25), moderate (OR 0.37, CI 0.04-3.57), or severe (OR 0.85, CI 0.09-8.42) myopes compared with emmetropes. Odds of any visual field defects were significantly increased in mild (OR 2.02, CI 1.28-3.19), moderate (OR 3.09, CI 1.42-6.72), and severe (OR 14.43, CI 5.13-40.61) myopes compared with emmetropes. The χ(2) test indicated a significant difference (P = 0.001) in the distribution of subjects with each category of visual field status across subjects with each refractive status; the proportion of subjects with worse visual field defects increased with worsening myopia severity.The association between myopia and visual field defects may represent an increased risk of glaucoma among myopes, and the lack of association with self-reported glaucoma may suggest a need for greater glaucoma surveillance in this population.
View details for DOI 10.1167/iovs.12-11158
View details for Web of Science ID 000314338400109
View details for PubMedID 23299483
- On the rate constants of OH + HO2 and HO2 + HO2: A comprehensive study of H2O2 thermal decomposition using multi-species laser absorption PROCEEDINGS OF THE COMBUSTION INSTITUTE 2013; 34: 565-571
mTORC1 and mTORC2 Play Different Roles in the Functional Survival of Transplanted Adipose-Derived Stromal Cells in Hind Limb Ischemic Mice Via Regulating Inflammation In Vivo
2013; 31 (1): 203-214
Poor cell survival severely limits the beneficial effects of stem cell therapy for peripheral arterial disease (PAD). This study was designed to investigate the role of mammalian target of rapamycin (mTOR) in the survival and therapeutic function of transplanted murine adipose-derived stromal cells (mADSCs) in a murine PAD model. mADSCs (1.0 × 10(7)) were isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein-positive transgenic mice, intramuscularly implanted into the hind limb of C57BL/6 mice after femoral artery ligation/excision, and monitored using noninvasive bioluminescence imaging (BLI). Although engrafted mADSCs produced antiapoptotic/proangiogenic effects in vivo by modulating the inflammatory and angiogenic cytokine response involving the mTOR pathway, longitudinal BLI revealed progressive death of post-transplant mADSCs within ~4 weeks in the ischemic hind limb. Selectively targeting mTOR complex-1 (mTORC1) using low-dose rapamycin treatment with mADSCs attenuated proinflammatory cytokines (interleukin [IL]-1β and tumor necrosis factor-alpha [TNF-α]) expression and neutrophil/macrophage infiltration, which overtly promoted mADSCs viability and antiapoptotic/proangiogenic efficacy in vivo. However, targeting dual mTORC1/mTORC2 using PP242 or high-dose rapamycin caused IL-1β/TNF-α upregulation and anti-inflammatory IL-10, IL-6, and vascular endothelial growth factor/vascular endothelial growth factor receptor 2 downregulation, undermining the survival and antiapoptotic/proangiogenic action of mADSCs in vivo. Furthermore, low-dose rapamycin abrogated TNF-α secretion by mADSCs and rescued the cells from hypoxia/reoxygenation-induced death in vitro, while PP242 or high-dose rapamycin exerted proinflammatory effects and promoted cell death. In conclusion, mTORC1 and mTORC2 may differentially regulate inflammation and affect transplanted mADSCs' functional survival in ischemic hind limb. These findings uncover that mTOR may evolve into a promising candidate for mechanism-driven approaches to facilitate the translation of cell-based PAD therapy.
View details for DOI 10.1002/stem.1265
View details for Web of Science ID 000312561000020
View details for PubMedID 23081858
Novel Application of Human Morphomics to Quantify Temporal Soft Tissues in Pierre Robin and Treacher Collins
JOURNAL OF CRANIOFACIAL SURGERY
2013; 24 (1): 158-162
Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls.High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized "core" sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant.The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group.There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.
View details for DOI 10.1097/SCS.0b013e3182646411
View details for Web of Science ID 000314853300079
View details for PubMedID 23348276
Improved Early Outcomes Using a T Cell Replete Graft Compared with T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
2012; 18 (12): 1835-1844
Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT.
View details for DOI 10.1016/j.bbmt.2012.07.003
View details for Web of Science ID 000311593900010
View details for PubMedID 22796535
Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system
Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy.
View details for DOI 10.1186/1476-4598-11-86
View details for Web of Science ID 000314051700001
View details for PubMedID 23171475
DNA Repair and Cell Cycle Biomarkers of Radiation Exposure and Inflammation Stress in Human Blood
2012; 7 (11)
DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS). Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06
View details for DOI 10.1371/journal.pone.0048619
View details for Web of Science ID 000311935800084
View details for PubMedID 23144912
A Magneto-Nanosensor Immunoassay for Sensitive Detection of Aspergillus Fumigatus Allergen Asp f 1
International Magnetics Conference (INTERMAG)
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2012: 3266–68
We report a magneto-nanosensor biochip for fungal detection. The chip is made of arrays of giant magnetoresistive (GMR) spin-valve sensors, and is able to detect protein biomarkers at low concentrations in solutions. As a demonstration, a standard curve for fungal pathogen Asp f 1 was obtained by measuring signals from various concentrations of Asp f 1 spiked in PBS solutions, indicating a detection limit of ~100 pg/ml. Five positive and negative Asp f 1 solution samples were discriminated correctly in blind experiments. Our data suggest that the magneto-nanosensor biochips are very promising as sensitive diagnostic devices for fungal pathogens. Given the generality of the detection scheme used in the magneto-nanosensor, we anticipate that the platform will be very useful for the detection of many types of biomarkers.
View details for DOI 10.1109/TMAG.2012.2195163
View details for Web of Science ID 000310194400137
- Nanoscale photon management in silicon solar cells JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A 2012; 30 (6)
A Current Sensor Based on the Giant Magnetoresistance Effect: Design and Potential Smart Grid Applications
2012; 12 (11): 15520-15541
Advanced sensing and measurement techniques are key technologies to realize a smart grid. The giant magnetoresistance (GMR) effect has revolutionized the fields of data storage and magnetic measurement. In this work, a design of a GMR current sensor based on a commercial analog GMR chip for applications in a smart grid is presented and discussed. Static, dynamic and thermal properties of the sensor were characterized. The characterizations showed that in the operation range from 0 to ±5 A, the sensor had a sensitivity of 28 mV·A(-1), linearity of 99.97%, maximum deviation of 2.717%, frequency response of −1.5 dB at 10 kHz current measurement, and maximum change of the amplitude response of 0.0335%·°C(-1) with thermal compensation. In the distributed real-time measurement and monitoring of a smart grid system, the GMR current sensor shows excellent performance and is cost effective, making it suitable for applications such as steady-state and transient-state monitoring. With the advantages of having a high sensitivity, high linearity, small volume, low cost, and simple structure, the GMR current sensor is promising for the measurement and monitoring of smart grids.
View details for DOI 10.3390/s121115520
View details for Web of Science ID 000311429500064
View details for PubMedID 23202221
FTO genotype is associated with phenotypic variability of body mass index
2012; 490 (7419): 267-?
There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
View details for DOI 10.1038/nature11401
View details for Web of Science ID 000309733300051
View details for PubMedID 22982992
View details for PubMedCentralID PMC3564953
Positron Emission Tomography of Cu-64-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL
MOLECULAR IMAGING AND BIOLOGY
2012; 14 (5): 608-616
This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.
View details for DOI 10.1007/s11307-011-0537-8
View details for Web of Science ID 000308819300011
View details for PubMedID 22231277
- Within- and among-genus components of size evolution during mass extinction, recovery, and background intervals: a case study of Late Permian through Late Triassic foraminifera PALEOBIOLOGY 2012; 38 (4): 627-643
- Optical Absorption Enhancement in Freestanding GaAs Thin Film Nanopyramid Arrays ADVANCED ENERGY MATERIALS 2012; 2 (10): 1254-1260
- Thermodynamic analysis of thermal hysteresis: Mechanistic insights into biological antifreezes JOURNAL OF CHEMICAL THERMODYNAMICS 2012; 53: 125-130
- Antibody lineages with evidence of somatic hypermutation persisting for > 4 years in a South African subject with broad neutralizing activity BIOMED CENTRAL LTD. 2012
- Pressure-induced tuning of a magnetic phase separation in Nd0.53Sr0.47MnO3 PHYSICAL REVIEW B 2012; 86 (9)
Prevalence and Predictors of Depression Among Participants With Glaucoma in a Nationally Representative Population Sample
AMERICAN JOURNAL OF OPHTHALMOLOGY
2012; 154 (3): 436-444
To investigate the prevalence of and risk factors for depression among participants with glaucoma and the predictive value of glaucoma for depression.Cross-sectional study.This study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, aged ≥40 years, who reported a presence or absence of glaucoma. Demographic and disease-related information was obtained by interview. Self-reported measures of vision were ascertained via items from the Visual Function Questionnaire (VFQ-25). Participants underwent visual acuity examination, fundus photography, and visual field testing with screening frequency-doubling technology (FDT N-30-5). The main outcome was presence of depression, as determined by a score ≥10 on the Patient Health Questionnaire-9 (PHQ-9).Prevalence of depression among participants with and without glaucoma was 10.9% (SEM 2.2%) and 6.9% (SEM 0.62%), respectively. While the presence of glaucoma was significantly associated with depression after adjustment for demographic factors (OR 1.80, 95% CI 1.16-2.79), this association was not significant after adjustment for self-reported general health condition (OR 1.35, 95% CI 0.822-2.23). Among participants with glaucoma, objective measures of glaucoma severity were not significant predictors for depression. However, several self-reported measures of visual function were significantly associated with depression.Glaucoma is a significant predictor of depression after adjustment for demographic factors and multiple comorbidities, but not after adjustment for self-reported general health condition. Among participants with glaucoma, self-reported measures of vision were significant risk factors for depression, whereas objective measures of vision were not.
View details for DOI 10.1016/j.ajo.2012.03.039
View details for Web of Science ID 000308115600005
View details for PubMedID 22789562
Modulating the Strength and Threshold of NOTCH Oncogenic Signals by mir-181a-1/b-1
2012; 8 (8)
Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR) signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.
View details for DOI 10.1371/journal.pgen.1002855
View details for Web of Science ID 000308529300016
View details for PubMedID 22916024
Fluorescent Magnetic Nanoparticles for Magnetically Enhanced Cancer Imaging and Targeting in Living Subjects
2012; 6 (8): 6862-6869
Early detection and targeted therapy are two major challenges in the battle against cancer. Novel imaging contrast agents and targeting approaches are greatly needed to improve the sensitivity and specificity of cancer theranostic agents. Here, we implemented a novel approach using a magnetic micromesh and biocompatible fluorescent magnetic nanoparticles (FMN) to magnetically enhance cancer targeting in living subjects. This approach enables magnetic targeting of systemically administered individual FMN, containing a single 8 nm superparamagnetic iron oxide core. Using a human glioblastoma mouse model, we show that nanoparticles can be magnetically retained in both the tumor neovasculature and surrounding tumor tissues. Magnetic accumulation of nanoparticles within the neovasculature was observable by fluorescence intravital microscopy in real time. Finally, we demonstrate that such magnetically enhanced cancer targeting augments the biological functions of molecules linked to the nanoparticle surface.
View details for DOI 10.1021/nn301670a
View details for Web of Science ID 000307988900039
View details for PubMedID 22857784
- Bonding and structural changes in siderite at high pressure AMERICAN MINERALOGIST 2012; 97 (8-9): 1421-1426
FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumourigenesis. The protein ataxia-telangiectasia mutated (ATM) is activated by DNA double-strand breaks and regulates apoptosis via p53. Here we show that FOXO3 interacts with the ATM-Chk2-p53 complex, augments phosphorylation of the complex and induces the formation of nuclear foci in cells on DNA damage. FOXO3 is essential for DNA damage-induced apoptosis and conversely FOXO3 requires ATM, Chk2 and phosphorylated p53 isoforms to trigger apoptosis as a result of DNA damage. Under these conditions FOXO3 may also have a role in regulating chromatin retention of phosphorylated p53. These results suggest an essential link between FOXO3 and the ATM-Chk2-p53-mediated apoptotic programme following DNA damage.
View details for DOI 10.1038/ncomms2008
View details for Web of Science ID 000308801100016
View details for PubMedID 22893124
View details for PubMedCentralID PMC3589124
- Author Response: The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 2012; 53 (8): 4940-4940
Heterotopic Ossification Following Burn Injury: The Role of Stem Cells
JOURNAL OF BURN CARE & RESEARCH
2012; 33 (4): 463-470
Heterotopic ossification (HO), or the abnormal development of bone tissue in soft-tissue locations, can be physically debilitating and clinically devastating. For unclear reasons, HO is highly associated with burn injury. The objective of this review is to summarize 1) cells that are responsible for HO, 2) in vitro and in vivo models of HO and how they have contributed to our current knowledge of the disease process, 3) the effects of the adipose compartment on HO, 4) the effects of inflammation on HO, and 5) the effects of mesenchymal stem cells (MSCs) on HO. Preclinical models of HO suggest several possible mechanisms for the development of this pathologic process, including progenitor cell differentiation and paracrine modulation of local inflammatory responses. Further studies are needed to elucidate the molecular mechanisms driving HO so that targeted therapies can be developed. Current literature supports a role for MSCs in modulating heterotopic bone formation, and direct manipulation of MSCs might one day be used to prevent and treat HO.
View details for DOI 10.1097/BCR.0b013e31825af547
View details for Web of Science ID 000306275000013
View details for PubMedID 22683987
Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota
2012; 149 (7): 1578-1593
Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.
View details for DOI 10.1016/j.cell.2012.04.037
View details for Web of Science ID 000305753800022
View details for PubMedID 22726443
- Differential Acoustic Resonance Spectroscopy for the acoustic measurement of small and irregular samples in the low frequency range JOURNAL OF GEOPHYSICAL RESEARCH-SOLID EARTH 2012; 117
Effects of ghrelin on homocysteine-induced dysfunction and inflammatory response in rat cardiac microvascular endothelial cells
CELL BIOLOGY INTERNATIONAL
2012; 36 (6): 511-517
Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs. In contrast, ghrelin pretreatment significantly improved proliferation and NO secretion, and inhibited cell apoptosis and secretion of cytokines in HCY-induced CMECs. In addition, Western blot assay showed that NF-κB (nuclear factor κB) and cleaved-caspase 3 expression were elevated, and PCNA (proliferating cell nuclear antigen) and eNOS (endothelial nitric oxide synthase) expression were decreased after treatment with HCY, which was significantly reversed by pretreatment with ghrelin. The data suggest that ghrelin inhibits HCY-induced CMEC dysfunction and inflammatory response, probably mediated by inhibition of NF-κB activation.
View details for DOI 10.1042/CBI20110235
View details for Web of Science ID 000305113500002
View details for PubMedID 22339616
Hybrid Silicon Nanocone-Polymer Solar Cells
2012; 12 (6): 2971-2976
Recently, hybrid Si/organic solar cells have been studied for low-cost Si photovoltaic devices because the Schottky junction between the Si and organic material can be formed by solution processes at a low temperature. In this study, we demonstrate a hybrid solar cell composed of Si nanocones and conductive polymer. The optimal nanocone structure with an aspect ratio (height/diameter of a nanocone) less than two allowed for conformal polymer surface coverage via spin-coating while also providing both excellent antireflection and light trapping properties. The uniform heterojunction over the nanocones with enhanced light absorption resulted in a power conversion efficiency above 11%. Based on our simulation study, the optimal nanocone structures for a 10 μm thick Si solar cell can achieve a short-circuit current density, up to 39.1 mA/cm(2), which is very close to the theoretical limit. With very thin material and inexpensive processing, hybrid Si nanocone/polymer solar cells are promising as an economically viable alternative energy solution.
View details for DOI 10.1021/nl300713x
View details for Web of Science ID 000305106400054
View details for PubMedID 22545674
- High pressure nano-tomography using an iterative method 6th International Conference on the Study of Matter at Extreme Conditions (SMEC) AMER INST PHYSICS. 2012
LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era
LEUKEMIA & LYMPHOMA
2012; 53 (6): 1105-1112
Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.
View details for DOI 10.3109/10428194.2011.638717
View details for Web of Science ID 000304311500016
View details for PubMedID 22066713
Regulation of selection and autoimmunity by miR-181 family miRNAs
99th Annual Meeting of the American-Association-of-Immunologists
AMER ASSOC IMMUNOLOGISTS. 2012
View details for Web of Science ID 000304659701313
Families of Superhard Crystalline Carbon Allotropes Constructed via Cold Compression of Graphite and Nanotubes
PHYSICAL REVIEW LETTERS
2012; 108 (13)
We report a general scheme to systematically construct two classes of structural families of superhard sp(3) carbon allotropes of cold-compressed graphite through the topological analysis of odd 5+7 or even 4+8 membered carbon rings stemmed from the stacking of zigzag and armchair chains. Our results show that the previously proposed M, bct-C(4), W and Z allotropes belong to our currently proposed families and that depending on the topological arrangement of the native carbon rings numerous other members are found that can help us understand the structural phase transformation of cold-compressed graphite and carbon nanotubes (CNTs). In particular, we predict the existence of two simple allotropes, R and P carbon, which match well the experimental x-ray diffraction patterns of cold-compressed graphite and CNTs, respectively, display a transparent wide-gap insulator ground state and possess a large Vickers hardness comparable to diamond.
View details for DOI 10.1103/PhysRevLett.108.135501
View details for Web of Science ID 000302019600007
View details for PubMedID 22540712
Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (10): E595-E604
The regulation of cell shape is a common challenge faced by organisms across all biological kingdoms. In nearly all bacteria, cell shape is determined by the architecture of the peptidoglycan cell wall, a macromolecule consisting of glycan strands crosslinked by peptides. In addition to shape, cell growth must also maintain the wall structural integrity to prevent lysis due to large turgor pressures. Robustness can be accomplished by establishing a globally ordered cell-wall network, although how a bacterium generates and maintains peptidoglycan order on the micron scale using nanometer-sized proteins remains a mystery. Here, we demonstrate that left-handed chirality of the MreB cytoskeleton in the rod-shaped bacterium Escherichia coli gives rise to a global, right-handed chiral ordering of the cell wall. Local, MreB-guided insertion of material into the peptidoglycan network naturally orders the glycan strands and causes cells to twist left-handedly during elongational growth. Through comparison with the right-handed twisting of Bacillus subtilis cells, our work supports a common mechanism linking helical insertion and chiral cell-wall ordering in rod-shaped bacteria. These physical principles of cell growth link the molecular structure of the bacterial cytoskeleton, mechanisms of wall synthesis, and the coordination of cell-wall architecture.
View details for DOI 10.1073/pnas.1117132109
View details for Web of Science ID 000301117700005
View details for PubMedID 22343529
- RESPONSE OF THE PHOTOSPHERIC MAGNETIC FIELD TO THE X2.2 FLARE ON 2011 FEBRUARY 15 ASTROPHYSICAL JOURNAL LETTERS 2012; 745 (2)
The Association between Glaucoma Prevalence and Supplementation with the Oxidants Calcium and Iron
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2012; 53 (2): 725-731
To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma.This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ≥ 40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview.Participants who consumed ≥ 800 mg/d of supplementary calcium or ≥ 18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25-4.76 for calcium; OR 3.80, 95% CI 1.79-8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42-21.62). A clear dose-response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found.These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.
View details for DOI 10.1167/iovs.11-9038
View details for Web of Science ID 000302788600024
View details for PubMedID 22247455
DNA Polyfluorophores for Real-Time Multicolor Tracking of Dynamic Biological Systems
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2012; 51 (29): 7176-7180
Dye-ing to live: Spectral limitations of common organic dyes make it difficult or impossible to visualize and follow multiple biological components in rapidly moving systems. The development of a multispectral set of improved DNA-scaffolded fluorophores is described. Their use in multicolor cellular imaging (see scheme) and in tracking of biological motions on the subsecond timescale is demonstrated.
View details for DOI 10.1002/anie.201201928
View details for Web of Science ID 000306314300020
View details for PubMedID 22684777
View details for PubMedCentralID PMC3489938
- Direct Fluorescence Monitoring of DNA Base Excision Repair ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2012; 51 (7): 1689-1692
Expanding the molecular recognition repertoire of antifreeze polypeptides: effects on nucleoside crystal growth
2012; 48 (94): 11555-11557
Despite differences in the crystal structures of ice and nucleosides, antifreeze polypeptides (AFPs) have been demonstrated to inhibit nucleation of 5-methyluridine, cytidine, and inosine and modify the crystal growth of the nucleosides efficiently. The molecular recognition repertoire of AFPs has been expanded to non-ice-like crystalline solids.
View details for DOI 10.1039/c2cc36264c
View details for Web of Science ID 000310459400019
View details for PubMedID 23089878
- The Gene Ontology: enhancements for 2011 NUCLEIC ACIDS RESEARCH 2012; 40 (D1): D559-D564
Templated chemistry for monitoring damage and repair directly in duplex DNA
2012; 48 (65): 8069-8071
We report the fluorogenic detection of the product of base excision repair (an abasic site) in a specific sequence of duplex DNA. This is achieved by DNA-templated chemistry, employing triple helix-forming probes that contain unnatural nucleobases designed to selectively recognize the site of a missing base. Light-up signals of up to 36-fold were documented, and probes could be used to monitor enzymatic removal of a damaged base.
View details for DOI 10.1039/c2cc34060g
View details for Web of Science ID 000306573800008
View details for PubMedID 22782065
- Spin wave modes in ferromagnetic tubes JOURNAL OF APPLIED PHYSICS 2012; 111 (1)
- Measurement of the jet fragmentation function and transverse profile in proton-proton collisions at a center-of-mass energy of 7 TeV with the ATLAS detector EUROPEAN PHYSICAL JOURNAL C 2011; 71 (11)
Interaction of reduced nicotinamide adenine dinucleotide with an antifreeze protein from Dendroides canadensis: mechanistic implication of antifreeze activity enhancement
JOURNAL OF MOLECULAR RECOGNITION
2011; 24 (6): 1025-1032
Antifreeze proteins (AFPs) found in many organisms can noncolligatively lower the freezing point of water without altering the melting point. The difference between the depressed freezing point and the melting point, termed thermal hysteresis (TH), is usually a measure of the antifreeze activity of AFPs. Certain low molecular mass molecules and proteins can further enhance the antifreeze activity of AFPs. Interaction between an enhancer and arginine is known to play an important role in enhancing the antifreeze activity of an AFP from the beetle Dendroides canadensis (DAFP-1). Here, we examined the enhancement effects of several prevalent phosphate-containing coenzymes on the antifreeze activity of DAFP-1. β-Nicotinamide adenine dinucleotide (reduced) (NADH) is identified as the most efficient enhancer of DAFP-1, which increases the antifreeze activity of DAFP-1 by around 10 times. Examination of the enhancement abilities of a series of NADH analogs and various molecular fragments of NADH reveals that the modifications of nicotinamide generate a series of highly efficient enhancers, though none as effective as NADH itself, and the whole molecular structure of NADH is necessary for its highly efficient enhancement effect. We also demonstrated a 1:1 binding between DAFP-1 and NADH. The binding was characterized by high-performance liquid chromatography (HPLC) using the gel filtration method of Hummel and Dreyer. The data analysis suggests binding between DAFP-1 and NADH with a dissociation constant in the micromolar range. Interactions between DAFP-1 and NADH are discussed along with molecular mechanisms of enhancer action.
View details for DOI 10.1002/jmr.1151
View details for Web of Science ID 000298599500014
View details for PubMedID 22038809
The bacterial actin MreB rotates, and rotation depends on cell-wall assembly
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2011; 108 (38): 15822-15827
Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the Escherichia coli actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.
View details for DOI 10.1073/pnas.1108999108
View details for Web of Science ID 000295030000036
View details for PubMedID 21903929
Scaling relations applied to synthetic fuel production
242nd National Meeting of the American-Chemical-Society (ACS)
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000299378303423
High pressure chemistry of silane and water
242nd National Meeting of the American-Chemical-Society (ACS)
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000299378300881
Polyfluorophores on a DNA backbone: Expanded spectrum and improved stability with new fluorophores
242nd National Meeting of the American-Chemical-Society (ACS)
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000299378305616
Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study
2011; 118 (6): 1591-1599
To lend clarity to inconsistent prior findings of an inverse association between ultraviolet radiation (UVR) exposure and risk of lymphoid malignancies, we examined the association of prospectively ascertained residential ambient UVR exposure with risk of non-Hodgkin lymphomas (NHLs), multiple myeloma (MM), and classical Hodgkin lymphoma in the California Teachers Study cohort. Among 121 216 eligible women, 629 were diagnosed with NHL, 119 with MM, and 38 with Hodgkin lymphoma between 1995-1996 and 2007. Cox proportional hazards regression was used to estimate incidence rate ratios (RRs) with 95% confidence intervals (CIs). Residential UVR levels within a 20-km radius were associated with reduced risk of overall NHL (RR for highest vs lowest statewide quartile of minimum UVR [≥ 5100 vs < 4915 W-h/m(2)], 0.58; 95% CI, 0.42-0.80), especially diffuse large B-cell lymphoma (RR, 0.36; 95% CI, 0.17-0.78) and chronic lymphocytic leukemia/small lymphocytic lymphoma (RR, 0.46; 95% CI, 0.21-1.01), and MM (RR for maximum UVR, 0.57; 95% CI, 0.36-0.90). These associations were not modified by skin sensitivity to sunlight, race/ethnicity, body mass index, or neighborhood socioeconomic status. Dietary vitamin D also was not associated with risk of lymphoid malignancies. These results support a protective effect of routine residential UVR exposure against lymphomagenesis through mechanisms possibly independent of vitamin D.
View details for DOI 10.1182/blood-2011-02-336065
View details for Web of Science ID 000293787300026
View details for PubMedID 21622649
Silicon nano-well arrays for reliable pattern transfer and locally confined high temperature reactions
2011; 22 (30)
Si nano-well arrays, with precisely controlled undercut Si sidewall profiles and flat bottomed pockets, enable uniform nanoscale pattern transfer from resists to metal deposits without degradation of the initial lithographic resolution, as verified by the formation of arrays of Au nano-dots with 10 nm diameter. An additional functionality of the Si nano-wells as local nano-reactors, where the patterned material is enclosed in a Si pocket during high temperature reaction, is demonstrated by thermally inducing a phase transformation of the as-deposited A1 phase of FePt nano-dots to the high coercivity, chemically ordered L1(0) phase.
View details for DOI 10.1088/0957-4484/22/30/305304
View details for Web of Science ID 000292455300006
View details for PubMedID 21709347
- Quantitative Analysis of CME Deflections in the Corona SOLAR PHYSICS 2011; 271 (1-2): 111-139
Room Temperature Current Injection Polariton Light Emitting Diode with a Hybrid Microcavity
2011; 11 (7): 2791-2795
The strong light-matter interaction within a semiconductor high-Q microcavity has been used to produce half-matter/half-light quasiparticles, exciton-polaritons. The exciton-polaritons have very small effective mass and controllable energy-momentum dispersion relation. These unique properties of polaritons provide the possibility to investigate the fundamental physics including solid-state cavity quantum electrodynamics, and dynamical Bose-Einstein condensates (BECs). Thus far the polariton BEC has been demonstrated using optical excitation. However, from a practical viewpoint, the current injection polariton devices operating at room temperature would be most desirable. Here we report the first realization of a current injection microcavity GaN exciton-polariton light emitting diode (LED) operating under room temperature. The exciton-polariton emission from the LED at photon energy 3.02 eV under strong coupling condition is confirmed through temperature-dependent and angle-resolved electroluminescence spectra.
View details for DOI 10.1021/nl2011164
View details for Web of Science ID 000292849400039
View details for PubMedID 21675759
ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
2011; 12 (7): 713-719
The cellular response to double-strand breaks (DSBs) in DNA is a complex signalling network, mobilized by the nuclear protein kinase ataxia-telangiectasia mutated (ATM), which phosphorylates many factors in the various branches of this network. A main question is how ATM regulates DSB repair. Here, we identify the DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) as an ATM target. PNKP phosphorylates 5'-OH and dephosphorylates 3'-phosphate DNA ends that are formed at DSB termini caused by DNA-damaging agents, thereby regenerating legitimate ends for further processing. We establish that the ATM phosphorylation targets on human PNKP-Ser 114 and Ser 126-are crucial for cellular survival following DSB induction and for effective DSB repair, being essential for damage-induced enhancement of the activity of PNKP and its proper accumulation at the sites of DNA damage. These findings show a direct functional link between ATM and the DSB-repair machinery.
View details for DOI 10.1038/embor.2011.96
View details for Web of Science ID 000292325700023
View details for PubMedID 21637298
On the behavior of Bronsted-Evans-Polanyi relations for transition metal oxides
JOURNAL OF CHEMICAL PHYSICS
2011; 134 (24)
Versatile Brønsted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site, and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strong intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a "cyclic" behavior in the transition state characteristics upon change of the active transition metal of the oxide.
View details for DOI 10.1063/1.3602323
View details for Web of Science ID 000292331900043
View details for PubMedID 21721645
Comparison of Three Embryo Culture Methods for Derivation of Human Embryonic Stem Cells from Discarded Embryos
2011; 13 (3): 233-239
Human embryonic stem cells (hESC) are self-renewing and pluripotent cells that hold great promise. Our objective was to compare the effect of three different embryo culture methods for derivation of human embryonic stem cells from discarded embryos. A prospective and randomized trial was conducted using 381 discarded human embryos at days 2-3 postfertilization in Beijing Obstetrics and Gynecology Hospital IVF center. After removal of the zona pellucida, discarded human embryos were cultured by three different methods as multiple embryo aggregates, single embryo, and blastomeres. Outgrowth of embryos and hESC derivation were observed. The outgrowth rate of embryos cultured as multiple embryo aggregates was higher than that of those cultured as single embryos or blastomeres (p < 0.05). Three propagating hESC lines were derived from poor quality day 2-3 postfertilization nonblastocyst embryos cultured as multiple embryo aggregates. Derived hESC lines expressed hESC-specific markers of pluripotency and had normal diploid karyotype. The cells were able to form derivatives of all three germ layers in vivo as teratomas. Our results demonstrate that culturing these discarded embryos as multiple embryo aggregates was more profitable for outgrowth and derivation of ESC line than culturing these as single embryo or blastomeres.
View details for DOI 10.1089/cell.2010.0092
View details for Web of Science ID 000291205400005
View details for PubMedID 21453052
Lymphoid Malignancies in US Asians: Incidence Rate Differences by Birthplace and Acculturation
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
2011; 20 (6): 1064-1077
Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHL), HL, and multiple myeloma, occur at much lower rates in Asians than other racial/ethnic groups in the United States. It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status.We obtained data about all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from U.S. Census data.Although incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than U.S.-born Asians with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower SES neighborhoods than those living elsewhere.These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL.Studying specific lymphoid malignancies in U.S. Asians may provide valuable insight toward understanding their environmental causes.
View details for DOI 10.1158/1055-9965.EPI-11-0038
View details for Web of Science ID 000291308600003
View details for PubMedID 21493873
Gravity Probe B: Final Results of a Space Experiment to Test General Relativity
PHYSICAL REVIEW LETTERS
2011; 106 (22)
Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3 mas/yr and a frame-dragging drift rate of -37.2±7.2 mas/yr, to be compared with the GR predictions of -6606.1 mas/yr and -39.2 mas/yr, respectively ("mas" is milliarcsecond; 1 mas=4.848×10(-9) rad).
View details for DOI 10.1103/PhysRevLett.106.221101
View details for Web of Science ID 000291093600003
View details for PubMedID 21702590
- Charged-particle multiplicities in pp interactions measured with the ATLAS detector at the LHC NEW JOURNAL OF PHYSICS 2011; 13
- Gradual pressure release for reliable nanoimprint lithography JOURNAL OF VACUUM SCIENCE & TECHNOLOGY B 2011; 29 (3)
- THE GEOZOIC SUPEREON PALAIOS 2011; 26 (5-6): 251-255
- Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks (vol 41, pg 529, 2011) MOLECULAR CELL 2011; 42 (1): 137-137
- Micro-structured ferromagnetic tubes for spin wave excitation JOURNAL OF APPLIED PHYSICS 2011; 109 (7)
GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma
2011; 7 (4)
Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined) = 0.64, P(combined) = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted) = 0.70, P(adjusted) = 4 × 10(-12); rs10484561:OR(adjusted) = 1.64, P(adjusted) = 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined) = 1.36, P(combined) = 1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
View details for DOI 10.1371/journal.pgen.1001378
View details for Web of Science ID 000289977000026
View details for PubMedID 21533074
Br(A)over-tilde,nsted-Evans-Polanyi relations for transition-metal oxides from density functional theory
241st National Meeting and Exposition of the American-Chemical-Society (ACS)
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000291982803874
Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks
2011; 41 (5): 529-542
The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase: the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.
View details for DOI 10.1016/j.molcel.2011.02.015
View details for Web of Science ID 000288150700006
View details for PubMedID 21362549
- Universal Bronsted-Evans-Polanyi Relations for C-C, C-O, C-N, N-O, N-N, and O-O Dissociation Reactions CATALYSIS LETTERS 2011; 141 (3): 370-373
Multispectral labeling of antibodies with polyfluorophores on a DNA backbone and application in cellular imaging
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2011; 108 (9): 3493-3498
Most current approaches to multiantigen fluorescent imaging require overlaying of multiple images taken with separate filter sets as a result of differing dye excitation requirements. This requirement for false-color composite imaging prevents the user from visualizing multiple species in real time and disallows imaging of rapidly moving specimens. To address this limitation, here we investigate the use of oligodeoxyfluoroside (ODF) fluorophores as labels for antibodies. ODFs are short DNA-like oligomers with fluorophores replacing the DNA bases and can be assembled in many colors with excitation at a single wavelength. A DNA synthesizer was used to construct several short ODFs carrying a terminal alkyne group and having emission maxima of 410-670 nm. We developed a new approach to antibody conjugation, using Huisgen-Sharpless cycloaddition, which was used to react the alkynes on ODFs with azide groups added to secondary antibodies. Multiple ODF-tagged secondary antibodies were then used to mark primary antibodies. The set of antibodies was tested for spectral characteristics in labeling tubulin in HeLa cells and revealed a wide spectrum of colors, ranging from violet-blue to red with excitation through a single filter (340-380 nm). Selected sets of the differently labeled secondary antibodies were then used to simultaneously mark four antigens in fixed cells, using a single image and filter set. We also imaged different surface tumor markers on two live cell lines. Experiments showed that all colors could be visualized simultaneously by eye under the microscope, yielding multicolor images of multiple cellular antigens in real time.
View details for DOI 10.1073/pnas.1017349108
View details for Web of Science ID 000287844400014
View details for PubMedID 21321224
- Wafer-Level Epitaxial Silicon Packaging for Out-of-Plane RF MEMS Resonators with Integrated Actuation Electrodes IEEE TRANSACTIONS ON COMPONENTS PACKAGING AND MANUFACTURING TECHNOLOGY 2011; 1 (3): 310-317
PROSPECTIVE RANDOMIZED DOUBLE-BLIND PILOT STUDY OF SITE-SPECIFIC CONSENSUS ATLAS IMPLEMENTATION FOR RECTAL CANCER TARGET VOLUME DELINEATION IN THE COOPERATIVE GROUP SETTING
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2011; 79 (2): 481-489
Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes.A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement).Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure.Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.
View details for DOI 10.1016/j.ijrobp.2009.11.012
View details for Web of Science ID 000286451000023
View details for PubMedID 20400244
View details for PubMedCentralID PMC2929319
- Magnetic, Mechanical, and Optical Characterization of a Magnetic Nanoparticle-Embedded Polymer for Microactuation JOURNAL OF MICROELECTROMECHANICAL SYSTEMS 2011; 20 (1): 65-72
- Testing relativity with orbiting clocks ADVANCES IN SPACE RESEARCH 2011; 47 (3): 525-527
Dietary phytocompounds and risk of lymphoid malignancies in the California Teachers Study cohort
CANCER CAUSES & CONTROL
2011; 22 (2): 237-249
We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.Between 1995-1996 and 31 December 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day = 0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 μM Trolox equiv/g/day = 0.68, 95% CI: 0.42-1.10; p (trend) = 0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease the risk of selected subtypes.
View details for DOI 10.1007/s10552-010-9692-5
View details for Web of Science ID 000286465000009
View details for PubMedID 21107674
Fluorescent DNA chemosensors: identification of bacterial species by their volatile metabolites
2011; 47 (41): 11435-11437
Polyfluorophores built on a DNA scaffold (ODFs) were synthesized and tested for fluorescence responses to the volatiles from M. tuberculosis, E. coli and P. putida in closed Petri dishes. Two sensors in a pattern-based response could distinguish the bacterial strains accurately, suggesting the use of ODFs in rapid identification of infectious agents.
View details for DOI 10.1039/c1cc14871k
View details for Web of Science ID 000295696300011
View details for PubMedID 21935547
Combinatorial synthesis of galactosyl-1,3,5-triazines as novel nucleoside analogues
ORGANIC & BIOMOLECULAR CHEMISTRY
2011; 9 (20): 6924-6926
Herein we report a parallel solid-phase synthesis of 1,3,5-triazine based nucleoside analogues by a three-step substitution, starting from 2,4,6-trichloro-1,3,5-triazine. A library of 80 galactosyl-1,3,5-triazine compounds was prepared in high purity without extensive reaction conditions or tedious purification, suggesting the generality of this method.
View details for DOI 10.1039/c1ob05733b
View details for Web of Science ID 000295889900009
View details for PubMedID 21863155
Universal transition state scaling relations for (de)hydrogenation over transition metals
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2011; 13 (46): 20760-20765
We analyse the transition state energies for 249 hydrogenation/dehydrogenation reactions of atoms and simple molecules over close-packed and stepped surfaces and nanoparticles of transition metals using Density Functional Theory. Linear energy scaling relations are observed for the transition state structures leading to transition state scaling relations for all the investigated reactions. With a suitable choice of reference systems the transition state scaling relations form a universality class that can be approximated with one single linear relation describing the entire range of reactions over all types of surfaces and nanoclusters.
View details for DOI 10.1039/c1cp20547a
View details for Web of Science ID 000297071400029
View details for PubMedID 21996683
The evolutionary consequences of oxygenic photosynthesis: a body size perspective
2011; 107 (1): 37-57
The high concentration of molecular oxygen in Earth's atmosphere is arguably the most conspicuous and geologically important signature of life. Earth's early atmosphere lacked oxygen; accumulation began after the evolution of oxygenic photosynthesis in cyanobacteria around 3.0-2.5 billion years ago (Gya). Concentrations of oxygen have since varied, first reaching near-modern values ~600 million years ago (Mya). These fluctuations have been hypothesized to constrain many biological patterns, among them the evolution of body size. Here, we review the state of knowledge relating oxygen availability to body size. Laboratory studies increasingly illuminate the mechanisms by which organisms can adapt physiologically to the variation in oxygen availability, but the extent to which these findings can be extrapolated to evolutionary timescales remains poorly understood. Experiments confirm that animal size is limited by experimental hypoxia, but show that plant vegetative growth is enhanced due to reduced photorespiration at lower O(2):CO(2). Field studies of size distributions across extant higher taxa and individual species in the modern provide qualitative support for a correlation between animal and protist size and oxygen availability, but few allow prediction of maximum or mean size from oxygen concentrations in unstudied regions. There is qualitative support for a link between oxygen availability and body size from the fossil record of protists and animals, but there have been few quantitative analyses confirming or refuting this impression. As oxygen transport limits the thickness or volume-to-surface area ratio-rather than mass or volume-predictions of maximum possible size cannot be constructed simply from metabolic rate and oxygen availability. Thus, it remains difficult to confirm that the largest representatives of fossil or living taxa are limited by oxygen transport rather than other factors. Despite the challenges of integrating findings from experiments on model organisms, comparative observations across living species, and fossil specimens spanning millions to billions of years, numerous tractable avenues of research could greatly improve quantitative constraints on the role of oxygen in the macroevolutionary history of organismal size.
View details for DOI 10.1007/s11120-010-9593-1
View details for Web of Science ID 000286199300004
View details for PubMedID 20821265
Alcohol Consumption Over Time and Risk of Lymphoid Malignancies in the California Teachers Study Cohort
AMERICAN JOURNAL OF EPIDEMIOLOGY
2010; 172 (12): 1373-1383
Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.
View details for DOI 10.1093/aje/kwq309
View details for Web of Science ID 000285193200008
View details for PubMedID 20952595
- Readiness of the ATLAS Tile Calorimeter for LHC collisions EUROPEAN PHYSICAL JOURNAL C 2010; 70 (4): 1193-1236
Essential Role for Mir-181a1/b1 In T-Cell Acute Lymphoblastic Leukemia
52nd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)
AMER SOC HEMATOLOGY. 2010: 209–10
View details for Web of Science ID 000289662200471
Evaluation of cationic nanoparticles of biodegradable copolymers as siRNA delivery system for hepatitis B treatment
INTERNATIONAL JOURNAL OF PHARMACEUTICS
2010; 400 (1-2): 194-200
Cationic nanoparticles of biodegradable polymers such as poly (lactide) (PLA) have been shown to be promising carrier systems for DNA and siRNA delivery. However, the parameters which influence the transfection efficiency have not been investigated in details. In this work, four groups of cationic PLA-based nanoparticles were synthesized by the nanoprecipitation method and solvent evaporation method with polyethyleneimine (PEI) and chitosan as two types of surface coating materials. Cationic poly (D,L-lactide-co-glycolide) (PLGA)-PEI, PLGA-chitosan and methoxy poly (ethylene glycol)-poly (lactide) (mPEG)-PLA/PEI, mPEG-PLA-chitosan nanoparticles were characterized in terms of size and size distribution by laser scattering, surface charge by zeta potential measurement, and surface chemistry by X-ray electron spectroscopy (XPS). The four type pg nanoparticles were compared for their interaction with siRNA and nanoparticles mediated siRNA transfection efficiency with a hepatitis B model, where the inhibition effects of the double strand RNA (dsRNA) mediated by the four types of nanoparticles were evaluated by measuring the HBsAg expression level. The highest inhibition effect of HBsAg (the surface antigen of the hepatitis B Virus (HBV), which indicates current hepatitis B infection) expression was achieved by the mPEG-PLA-PEI nanoparticles mediated siRNA transfection. The results demonstrated that the siRNA delivery follows a size and surface charge dependant manner.
View details for DOI 10.1016/j.ijpharm.2010.08.026
View details for Web of Science ID 000283829900025
View details for PubMedID 20801205
A map of human genome variation from population-scale sequencing
2010; 467 (7319): 1061-1073
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.
View details for DOI 10.1038/nature09534
View details for Web of Science ID 000283548600039
View details for PubMedCentralID PMC3042601
- High-pressure evolution of Fe2O3 electronic structure revealed by x-ray absorption PHYSICAL REVIEW B 2010; 82 (14)
Search for New Particles in Two-Jet Final States in 7 TeV Proton-Proton Collisions with the ATLAS Detector at the LHC
PHYSICAL REVIEW LETTERS
2010; 105 (16)
A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315 nb⁻¹ collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C.L. the q* mass interval 0.30
View details for DOI 10.1103/PhysRevLett.105.161801
View details for Web of Science ID 000282753000004
View details for PubMedID 21230962
- The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models PHARMACOGENOMICS JOURNAL 2010: S5-S16
Influence of coronal holes on CMEs in causing SEP events
RESEARCH IN ASTRONOMY AND ASTROPHYSICS
2010; 10 (10): 1049-1060
View details for Web of Science ID 000283763000008
- Pressure-induced behavior of the hydrogen-dominant compound SiH4(H-2)(2) from first-principles calculations PHYSICAL REVIEW B 2010; 82 (10)
Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
2010; 42 (8): 661-664
To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
View details for DOI 10.1038/ng.626
View details for Web of Science ID 000280524000008
View details for PubMedID 20639881
View details for PubMedCentralID PMC2913472
Targeted tumor gene therapy based on loss of IGF2 imprinting
CANCER BIOLOGY & THERAPY
2010; 10 (3)
Loss of imprinting (LOI) of the insulin-like growth factor 2 gene (IGF2) is one of the most common epigenetic abnormalities seen in human neoplasms. LOI may be associated with the lack of Zinc-finger DNA binding protein CTCF-mediated enhancer insulation, presumably due to the gain of methylation on the maternal allele of the differentially methylated domain (DMD) of the imprinting control region. This results in an interaction between the IGF2 promoters and enhancers; and IGF2 is produced from both alleles. In this study we investigated the feasibility of a novel anti-cancer adenovirus (AdDC312-DT-A) driven by H19 enhancer DMD-H19 promoter complex. Cell lines with IGF2 LOI (HCT-8, HT-29 and H-522) that were infected with AdDC312-EGFP produced the EGFP protein. However, in cells in which imprinting was maintained (MOI) (MCF-7 and GES-1), no EGFP protein was produced. The AdDC312-DT-A significantly decreased cell viability and induced apoptosis only in LOI cells in vitro, and suppressed tumour development in HCT-8 xenografts in nude mice. In conclusion, the toxin gene therapy proves effective in inhibiting LOI cell growth in vitro and in vivo and provides a novel option for targeted gene therapy based on loss of IGF2 imprinting.
View details for Web of Science ID 000281005600012
View details for PubMedID 20592487
Magneto-Nano Chips for Ultrasensitive and Multiplex Detection of Biomarkers of Tumor and Exposure
41st Annual Meeting of Environmental-Mutagen-Society
WILEY-BLACKWELL. 2010: 699–99
View details for Web of Science ID 000281009600059
The MicroArray Quality Control (MAQC)-IIII study of common practices for the development and validation of microarray-based predictive models
2010; 28 (8): 827-U109
Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.
View details for DOI 10.1038/nbt.1665
View details for Web of Science ID 000280757500023
View details for PubMedID 20676074
View details for PubMedCentralID PMC3315840
Extended-release fluvoxamine and improvements in quality of life in patients with obsessive-compulsive disorder
2010; 51 (4): 373-379
We hypothesized that subjects with obsessive-compulsive disorder (OCD) who received extended-release fluvoxamine (fluvoxamine ER) in a 12-week placebo-controlled trial would exhibit improvements in psychosocial domains of health-related quality of life (HRQOL) and that additional improvements would occur after a 40-week open-label extension trial. We also hypothesized that greater OCD symptom improvement in the first 12 weeks of treatment would be associated with greater HRQOL improvement after 52 weeks of treatment.In the 12-week placebo-controlled trial, subjects were randomized to receive placebo or 100 mg/d of fluvoxamine ER and then titrated in weekly 50 mg increments to a final dose of 100 to 300 mg/d. All subjects enrolled in the 40-week extension trial followed a similar titration, during which they were maintained on their highest well-tolerated dose.After 12 weeks of treatment, fluvoxamine ER subjects experienced significantly greater decreases than placebo subjects in Yale-Brown Obsessive-Compulsive Scale scores (P = .001). Both the active drug and placebo groups exhibited significant improvements in psychosocial domains of HRQOL; further improvement occurred after 40 weeks of open-label treatment with active drug. The greater the improvement in OCD severity at 12 weeks, the greater the improvement at 52 weeks in the psychosocial domains (Social Functioning r = -0.39, P = .027; Emotional Problems r = -0.37, P = .037; Mental Health r = -0.49, P = .004).Improvement in Yale-Brown Obsessive-Compulsive Scale severity scores during treatment with fluvoxamine ER was associated with improvements in psychosocial aspects of HRQOL that increased over an extended period of treatment.
View details for DOI 10.1016/j.comppsych.2009.10.001
View details for Web of Science ID 000279303500008
View details for PubMedID 20579510
Molecular Characterization of Myostatin Gene from Zhikong scallop Chlamys farreri (Jones et Preston 1904)
GENES & GENETIC SYSTEMS
2010; 85 (3): 207-218
The scallop is an economically important sea food prized for its large and delicious adductor muscle. Studying the molecular basis of scallop muscle growth is important for both scallop breeding and our understanding of muscle mass regulation in bivalve. Myostatin (MSTN) is a conserved negative regulator of muscle growth and development. Here we report the MSTN gene from Zhikong scallop (Chlamys farreri Jones et Preston 1904). The C. farreri MSTN consists of 11651 nucleotides encoding 457 amino acids. The gene has a 3-exon/2-intron structure that is conserved with vertebrate homologs. The exons are 586, 380 and 408 bp in length, respectively, and separated by introns of 5086 and 1518 bp. The protein sequence contains characteristic conserved residues including a cleavage motif of proteolysis (RXXR) and nine cysteines. Three transcription initiation sites were found at 62, 146, and 296 bp upstream of the translation start codon ATG. In silico analysis of the promoter region identified a TATA-box and several muscle-specific regulatory elements including COMP, MEF2s, MTBFs and E-boxes. Minisatellite DNA was found in intron 1. By fluorescence in situ hybridization (FISH), the gene was mapped to the long arm of a pair of middle subtelocentric chromosome. Quantitative analysis of MSTN transcripts in embryos/larvae indicated high expression level in gastrulae and limited expression at other stages. In adult scallops, MSTN is predominantly expressed in striated muscle, with different expression levels in other tissues. Our data provide valuable genomic and expression information which will aid the further study on scallop MSTN function and MSTN evolution.
View details for Web of Science ID 000285433600005
View details for PubMedID 21041979
- Analysis of Integrated Solenoid Inductor With Closed Magnetic Core IEEE TRANSACTIONS ON MAGNETICS 2010; 46 (6): 2387-2390
- Structural and magnetic characterizations of high moment synthetic antiferromagnetic nanoparticles fabricated using self-assembled stamps 11th Joint MMM-Intermag Conference AMER INST PHYSICS. 2010
- Silane-based functionalization of synthetic antiferromagnetic nanoparticles for biomedical applications 11th Joint MMM-Intermag Conference AMER INST PHYSICS. 2010
- Charged-particle multiplicities in pp interactions at root s=900 GeV measured with the ATLAS detector at the LHC ATLAS Collaboration PHYSICS LETTERS B 2010; 688 (1): 21-42
- Magnetic Nanotechnology for Biodetection JALA 2010; 15 (2): 93-98
Sensitive giant magnetoresistive-based immunoassay for multiplex mycotoxin detection
BIOSENSORS & BIOELECTRONICS
2010; 25 (7): 1635-1639
Rapid and multiplexed measurement is vital in the detection of food-borne pathogens. While highly specific and sensitive, traditional immunochemical assays such as enzyme-linked immunosorbent assays (ELISAs) often require expensive read-out equipment (e.g. fluorescent labels) and lack the capability of multiplex detection. By combining the superior specificity of immunoassays with the sensitivity and simplicity of magnetic detection, we have developed a novel multiplex magnetic nanotag-based detection platform for mycotoxins that functions on a sub-picomolar concentration level. Unlike fluorescent labels, magnetic nanotags (MNTs) can be detected with inexpensive giant magnetoresistive (GMR) sensors such as spin-valve sensors. In the system presented here, each spin-valve sensor has an active area of 90 microm x 90 microm, arranged in an 8 x 8 array. Sample is added to the antibody-immobilized sensor array prior to the addition of the biotinylated detection antibody. The sensor response is recorded in real time upon the addition of streptavidin-linked MNTs on the chip. Here we demonstrate the simultaneous detection of multiple mycotoxins (aflatoxins B(1), zearalenone and HT-2) and show that a detection limit of 50 pg/mL can be achieved.
View details for DOI 10.1016/j.bios.2009.11.028
View details for Web of Science ID 000275978700013
View details for PubMedID 20047828
Cervical Cancer Incidence Among 6 Asian Ethnic Groups in the United States, 1996 Through 2004
2010; 116 (4): 949-956
Cervical cancer incidence was evaluated by histologic type, age at diagnosis, and disease stage for 6 Asian ethnic groups residing in the United States.Incidence rates were estimated for cervical squamous cell carcinoma (SCC) and adenocarcinoma by age and stage for 6 Asian ethnic groups-Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, and Vietnamese-in 5 US cancer registry areas during 1996 through 2004. For comparison, rates among non-Hispanic whites, non-Hispanic blacks, and Hispanics were also calculated.During 1996 through 2004, Vietnamese women had the highest (18.9 per 100,000) and Asian Indian/Pakistani women had the lowest (4.5) incidence of cervical cancer; this pattern was consistent by histologic type. Vietnamese women also had the highest incidence for localized (7.3) and regional (5.7) SCC and for localized (2.4) adenocarcinoma. Contrary to the plateau of SCC incidence apparent among white women by age 45 years, SCC rates continued to rise with age among Chinese, Filipina, Korean, and Vietnamese women.There exists large variation in invasive cervical cancer incidence patterns among Asian ethnic groups in the United States and in comparison with rates for blacks, Hispanics, and whites. Early detection and prevention strategies for cervical cancer among Asians require targeted strategies by ethnic group.
View details for DOI 10.1002/cncr.24843
View details for Web of Science ID 000274315800024
View details for PubMedID 20029972
- The influence of Fermi level pinning/depinning on the Schottky barrier height and contact resistance in Ge/CoFeB and Ge/MgO/CoFeB structures APPLIED PHYSICS LETTERS 2010; 96 (5)
- Detection of a single synthetic antiferromagnetic nanoparticle with an AMR nanostructure: comparison between simulations and experiments International Conference on Magnetism (ICM 2009) IOP PUBLISHING LTD. 2010
- Sedimentology, sedimentary petrology, and paleoecology of the monsoon-driven, fluvio-lacustrine Zhada Basin, SW-Tibet SEDIMENTARY GEOLOGY 2009; 222 (1-2): 27-41
- Gravity Probe B Data Analysis Workshop on Probing the Nature of Gravity - Confronting Theory and Experiment in Space SPRINGER. 2009: 53–69
Attractin gene deficiency contributes to testis vacuolization and sperm dysfunction in male mice
JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES
2009; 29 (6): 750-754
The effect of loss-of-function of Attractin (Atrn) on the male mouse reproduction system was examined in the study. The weights and pathological changes of testes and epididymes were compared between Atrn mutant (Atrn(mg-3J)) mice and wild-type mice (C3HeB/FeJ) at different months of age. The number and motility of sperms were measured in the mutant and control mice. Furthermore, the testicular lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these animals were detected. The fertility potential of the sperms was observed in vivo and in vitro. The results showed that the testes of 3-month-old Atrn (mg-3J) mice experienced no significantly different pathological changes from the control mice at the same month of age but the SDH activity was substantially reduced. In the 5-month-old mutant mice, as compared with the control mice, mild vacuolation was found in the testes, the density and motility of sperms were decreased in the epididymes, the sperm fertility was impaired and the testicular enzyme activity was reduced. It is concluded that the age-related Atrn gene progressively loses its function and can cause testis vacuolation and impaired sperm function, which may be responsible for the impairment of male reproductive ability.
View details for DOI 10.1007/s11596-009-0616-0
View details for Web of Science ID 000273129100016
View details for PubMedID 20037821
- Small-Resistance and High-Quality-Factor Magnetic Integrated Inductors on PCB IEEE TRANSACTIONS ON ADVANCED PACKAGING 2009; 32 (4): 780-787
- Designs for a Microfabricated Magnetic Sifter International Magnetics Conference 2009 (INTERMAG) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2009: 4884–87
- Magnetostatic Spin-Wave Modes in Ferromagnetic Tube International Magnetics Conference 2009 (INTERMAG) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2009: 4223–25
- Nonreciprocal Spin Waves in Co-Ta-Zr Films and Multilayers International Magnetics Conference 2009 (INTERMAG) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2009: 4215–18
Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture micro environments
2009; 11 (5): 1127-1134
Spatial patterning of proteins is a valuable technique for many biological applications and is the prevailing tool for defining microenvironments for cells in culture, a required procedure in developmental biology and tissue engineering research. However, it is still challenging to achieve protein patterns that closely mimic native microenvironments, such as gradient protein distributions with desirable mechanical properties. By combining projection dynamic mask lithography and protein engineering with non-canonical photosensitive amino acids, we demonstrate a simple, scalable strategy to fabricate any user-defined 2D or 3D stable gradient pattern with complex geometries from an artificial extracellular matrix (aECM) protein. We show that the elastic modulus and chemical nature of the gradient profile are biocompatible and allow useful applications in cell biological research.
View details for DOI 10.1007/s10544-009-9329-1
View details for Web of Science ID 000270679400019
View details for PubMedID 19495986
Nanosized corners for trapping and detecting magnetic nanoparticles
2009; 20 (38)
We present a device concept based on controlled micromagnetic configurations in a corner-shaped permalloy nanostructure terminated with two circular disks, specifically designed for the capture and detection of a small number of magnetic beads in suspension. A transverse head-to-head domain wall (TDW) placed at the corner of the structure plays the role of an attracting pole for magnetic beads. The TDW is annihilated in the terminating disks by applying an appropriate magnetic field, whose value is affected by the presence of beads chemically bound to the surface. In the case where the beads are not chemically bound to the surface, the annihilation of the TDW causes their release into the suspension. The variation of the voltage drop across the corner, due to the anisotropic magnetoresistance (AMR) while sweeping the magnetic field, is used to detect the presence of a chemically bound bead. The device response has been characterized by using both synthetic antiferromagnetic nanoparticles (disks of 70 nm diameter and 20 nm height) and magnetic nanobeads, for different thicknesses of the protective capping layer. We demonstrate the detection down to a single nanoparticle, therefore the device holds the potential for the localization and detection of small numbers of molecules immobilized on the particle's functionalized surface.
View details for DOI 10.1088/0957-4484/20/38/385501
View details for Web of Science ID 000269356900009
View details for PubMedID 19713593
Visualizing Implanted Tumors in Mice with Magnetic Resonance Imaging Using Magnetotactic Bacteria
CLINICAL CANCER RESEARCH
2009; 15 (16): 5170-5177
To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (approximately 25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor.We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6.Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.
View details for DOI 10.1158/1078-0432.CCR-08-3206
View details for Web of Science ID 000269024900019
View details for PubMedID 19671860
High Resolution Crystal Structure of the Methylcobalamin Analogues Ethylcobalamin and Butylcobalamin by X-ray Synchrotron Diffraction
2009; 48 (14): 6615-6622
The X-ray crystal structures of the methylcobalamin (MeCbl) analogues ethylcobalamin (EtCbl) and butylcobalamin (BuCbl) are reported. The X-ray crystal structures of EtCbl and BuCbl were obtained with some of the lowest crystallographic residuals ever achieved for cobalamins (R = 0.0468 and 0.0438, respectively). The Co-C bond distances for EtCbl and BuCbl are 2.023(2) and 2.028(4) A, whereas the Co-alpha-5,6-dimethylbenzimidazole (Co-N3B) bond distances were 2.232(1) and 2.244(1) A, respectively. Although EtCbl and BuCbl displayed a longer Co-N3B bond than that observed in the naturally occurring methylcobalamin, the orientation of the alpha-5,6-dimethylbenzimidazole moiety with respect to the corrin ring did not vary substantially among the structures. The lengthening of both Co-C and Co-N3B bonds in EtCbl and BuCbl can be attributed to the "inverse" trans influence exerted by the sigma-donating alkyl groups, typically observed in alkylcobalamins. Analysis of the molecular surface maps showed that the alkyl ligands in EtCbl and BuCbl are directed toward the hydrophobic side of the corrin ring. The corrin fold angles in EtCbl and BuCbl were determined to be 14.7 degrees and 13.1 degrees, respectively. A rough correlation exists between the corrin fold angle and the length of the Co-N3B bond, and both alkylcobalamins follow the same trend.
View details for DOI 10.1021/ic900590p
View details for Web of Science ID 000268137900042
View details for PubMedID 19545130
- Cryogenic tilt table INTERNATIONAL JOURNAL OF PRECISION ENGINEERING AND MANUFACTURING 2009; 10 (3): 37-42
Formation and properties of magnetic chains for 100nm nanoparticles used in separations of molecules and cells
7th International Conference on Scientific and Clinical Applications of Magnetic Carriers
ELSEVIER SCIENCE BV. 2009: 1452–58
Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations of 10(10) per mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immunomagnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.
View details for DOI 10.1016/j.jmmm.2009.02.066
View details for Web of Science ID 000265278000028
- Synthetic antiferromagnetic nanoparticles with tunable susceptibilities 53rd Annual Conference on Magnetism and Magnetic Materials AMER INST PHYSICS. 2009
- Dispersion and spin wave "tunneling" in nanostructured magnetostatic spin waveguides 53rd Annual Conference on Magnetism and Magnetic Materials AMER INST PHYSICS. 2009
Effects of polyhydroxy compounds on beetle antifreeze protein activity
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
2009; 1794 (2): 341-346
Antifreeze proteins (AFPs) noncolligatively depress the nonequilibrium freezing point of a solution and produce a difference between the melting and freezing points termed thermal hysteresis (TH). Some low-molecular-mass solutes can affect the TH values. The TH enhancement effects of selected polyhydroxy compounds including polyols and carbohydrates on an AFP from the beetle Dendroides canadensis were systematically investigated using differential scanning calorimetry (DSC). The number of hydroxyl groups dominates the molar enhancement effectiveness of polyhydroxy compounds having one to five hydroxyl groups. However, the above rule does not apply for polyhydroxy compounds having more than five hydroxyl groups. The most efficient polyhydroxy enhancer identified is trehalose. In a combination of enhancers the strongest enhancer plays the major role in determining the TH enhancement. Mechanistic insights into identification of highly efficient AFP enhancers are discussed.
View details for DOI 10.1016/j.bbapap.2008.10.011
View details for Web of Science ID 000262952600022
View details for PubMedID 19038370
- Dispersion in magnetostatic CoTaZr spin waveguides APPLIED PHYSICS LETTERS 2009; 94 (1)
- Gravity Probe B(*) RIVISTA DEL NUOVO CIMENTO 2009; 32 (11): 555-589
Biological Variations in Depression and Anxiety Between East and West
CNS NEUROSCIENCE & THERAPEUTICS
2009; 15 (3): 283-294
Ethnicity and culture represent important factors in shaping psychopathology as well as pharmacotherapeutic responses in psychiatric patients. A large body of literature, accumulated over the past several decades, demonstrates that these factors not only determine the metabolism and disposition of medications (pharmacokinetics), but also their interactions with therapeutic targets (pharmacodynamics). This article focuses on the impact of such variations on the diagnosis and treatment of depression and anxiety disorders between East and West. Genes controlling the expression of drug metabolizing enzymes as well as the function of the brain are highly polymorphic, and the patterns and distribution of these polymorphisms are typically divergent across ethnic groups. To the extent that these genetic patterns determine drug response, ethnic variations in these genetic dispositions will lead to differential responses in clinical settings. In addition, the expression of these genes is significantly influenced by environmental factors including diet as well as exposure to other natural products. Superimposed on these biological influences, culturally determined beliefs and behavioral patterns also profoundly influence patients' expectations of treatment response, adherence, and interactions with clinicians. In addition to pharmacotherapeutic responses, emerging data also indicate that significant ethnic variations exist in genetic polymorphisms and neurobiologic correlates (biomarkers) that may be associated with the vulnerability to psychiatric disorders. These considerations argue for the importance of examining biological variations across ethnic groups, especially in the clinical context, in terms of the assessment and treatment of psychiatric patients, and in our understanding of psychiatric phenomenology and nosology.
View details for DOI 10.1111/j.1755-5949.2009.00093.x
View details for Web of Science ID 000268790700010
View details for PubMedID 19691548
Genome-wide transcriptome analysis of 150 cell samples
2009; 1 (1): 99-107
A major challenge in molecular biology is interrogating the human transcriptome on a genome wide scale when only a limited amount of biological sample is available for analysis. Current methodologies using microarray technologies for simultaneously monitoring mRNA transcription levels require nanogram amounts of total RNA. To overcome the sample size limitation of current technologies, we have developed a method to probe the global gene expression in biological samples as small as 150 cells, or the equivalent of approximately 300 pg total RNA. The new method employs microfluidic devices for the purification of total RNA from mammalian cells and ultra-sensitive whole transcriptome amplification techniques. We verified that the RNA integrity is preserved through the isolation process, accomplished highly reproducible whole transcriptome analysis, and established high correlation between repeated isolations of 150 cells and the same cell culture sample. We validated the technology by demonstrating that the combined microfluidic and amplification protocol is capable of identifying biological pathways perturbed by stimulation, which are consistent with the information recognized in bulk-isolated samples.
View details for DOI 10.1039/b814329c
View details for Web of Science ID 000266978200011
View details for PubMedID 20023796
A Prospective Randomized Pilot Study of Site-specific Atlas Incorporation into Target Volume Delineation Instructions in the Cooperative Group Setting: Preliminary Results from a Southwest Oncology Group Pilot using Big Brother
51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO)
ELSEVIER SCIENCE INC. 2009: S136–S137
View details for Web of Science ID 000270573600292
Inhibition of Drosophila Wg Signaling Involves Competition between Mad and Armadillo/beta-Catenin for dTcf Binding
2008; 3 (12)
Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor beta (TGFbeta)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector beta-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf.
View details for DOI 10.1371/journal.pone.0003893
View details for Web of Science ID 000265455200008
View details for PubMedID 19065265
Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004
CANCER CAUSES & CONTROL
2008; 19 (10): 1171-1181
To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups.Incident rates were estimated by age and sex for six Asian ethnic groups--Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese--in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated.During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype.The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.
View details for DOI 10.1007/s10552-008-9184-z
View details for Web of Science ID 000260766300017
View details for PubMedID 18543071
Polycarboxylates enhance beetle antifreeze protein activity
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
2008; 1784 (12): 1942-1948
Antifreeze proteins (AFPs) lower the noncolligative freezing point of water in the presence of ice below the ice melting point. The temperature difference between the melting point and the noncolligative freezing point is termed thermal hysteresis (TH). The magnitude of the TH depends on the specific activity and the concentration of AFP, and the concentration of enhancers in the solution. Known enhancers are certain low molecular mass molecules and proteins. Here, we investigated a series of polycarboxylates that enhance the TH activity of an AFP from the beetle Dendroides canadensis (DAFP) using differential scanning calorimetry (DSC). Triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetate, the most efficient enhancer identified in this work, can increase the TH of DAFP by nearly 1.5 fold over than that of the published best enhancer, citrate. The Zn(2+) coordinated carboxylate results in loss of the enhancement ability of the carboxylate on antifreeze activity. There is not an additional increase in TH when a weaker enhancer is added to a stronger enhancer solution. These observations suggest that the more carboxylate groups per enhancer molecule the better the efficiency of the enhancer and that the freedom of motion of these molecules is necessary for them to serve as enhancers for AFP. The hydroxyl groups in the enhancer molecules can also positively affect their TH enhancement efficiency, though not as strongly as carboxylate groups. Mechanisms are discussed.
View details for DOI 10.1016/j.bbapap.2008.06.003
View details for Web of Science ID 000261673300007
View details for PubMedID 18620083
- Integrated Microstrip Lines With Co-Ta-Zr Magnetic Films IEEE International Magnetics Conference (INTERMAG) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2008: 3103–6
Giant Magnetoresistive Sensors for DNA Microarray
IEEE International Magnetics Conference (INTERMAG)
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2008: 3989–91
Giant magnetoresistive (GMR) sensors are developed for a DNA microarray. Compared with the conventional fluorescent sensors, GMR sensors are cheaper, more sensitive, can generate fully electronic signals, and can be easily integrated with electronics and microfluidics. The GMR sensor used in this work has a bottom spin valve structure with an MR ratio of 12%. The single-strand target DNA detected has a length of 20 bases. Assays with DNA concentrations down to 10 pM were performed, with a dynamic range of 3 logs. A double modulation technique was used in signal detection to reduce the 1/f noise in the sensor while circumventing electromagnetic interference. The logarithmic relationship between the magnetic signal and the target DNA concentration can be described by the Temkin isotherm. Furthermore, GMR sensors integrated with microfluidics has great potential of improving the sensitivity to 1 pM or below, and the total assay time can be reduced to less than 1 hour.
View details for DOI 10.1109/TMAG.2008.2002795
View details for Web of Science ID 000262221300159
- Fabrication and Analysis of High-Performance Integrated Solenoid Inductor With Magnetic Core IEEE International Magnetics Conference (INTERMAG) IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2008: 4089–95
- Determining wave vector and material property from the phase-shift of spin-wave propagation EPL 2008; 84 (2)
TEM analyses of synthetic anti-ferromagnetic (SAF) nanoparticles fabricated using different release layers
11th Conference on Frontiers of Electron Microscopy in Materials Science
ELSEVIER SCIENCE BV. 2008: 1490–94
This paper investigates the structural characteristics of templated synthetic anti-ferromagnetic (SAF) magnetic nanoparticles fabricated on two different release layers. When copper was used as the latter, the layered structure of the SAFs was found to be disrupted with wavy multi-layers due to the formation of copper grains from the release layer. By introducing oxygen into the copper release layer before the deposition of the film, the topography of the oxidized copper grains was effectively controlled. This led to the fabrication of SAF nanoparticles with flat multi-layers.
View details for DOI 10.1016/j.ultramic.2008.03.012
View details for Web of Science ID 000260518200014
View details for PubMedID 18672328
- Advances in giant magnetoresistance biosensors with magnetic nanoparticle tags: Review and outlook IEEE TRANSACTIONS ON MAGNETICS 2008; 44 (7): 1687-1702
Nanoscale control of exchange bias with BiFeO3 thin films
2008; 8 (7): 2050-2055
We demonstrate a direct correlation between the domain structure of multiferroic BiFeO3 thin films and exchange bias of Co 0.9Fe 0.1/BiFeO3 heterostructures. Two distinct types of interactions - an enhancement of the coercive field ( exchange enhancement) and an enhancement of the coercive field combined with large shifts of the hysteresis loop ( exchange bias) - have been observed in these heterostructures, which depend directly on the type and crystallography of the nanoscale ( approximately 2 nm) domain walls in the BiFeO3 film. We show that the magnitude of the exchange bias interaction scales with the length of 109 degrees ferroelectric domain walls in the BiFeO 3 thin films which have been probed via piezoresponse force microscopy and X-ray magnetic circular dichroism.
View details for DOI 10.1021/nl801391m
View details for Web of Science ID 000257504500046
View details for PubMedID 18547121
The Red Queen revisited: reevaluating the age selectivity of Phanerozoic marine genus extinctions
2008; 34 (3): 318-341
View details for Web of Science ID 000258212400002
LMO2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma (DLBCL)
10th International Conference on Malignant Lymphoma
OXFORD UNIV PRESS. 2008: 107–107
View details for Web of Science ID 000256693500092
Electric-field control of local ferromagnetism using a magnetoelectric multiferroic
2008; 7 (6): 478-482
Multiferroics are of interest for memory and logic device applications, as the coupling between ferroelectric and magnetic properties enables the dynamic interaction between these order parameters. Here, we report an approach to control and switch local ferromagnetism with an electric field using multiferroics. We use two types of electromagnetic coupling phenomenon that are manifested in heterostructures consisting of a ferromagnet in intimate contact with the multiferroic BiFeO(3). The first is an internal, magnetoelectric coupling between antiferromagnetism and ferroelectricity in the BiFeO(3) film that leads to electric-field control of the antiferromagnetic order. The second is based on exchange interactions at the interface between a ferromagnet (Co(0.9)Fe(0.1)) and the antiferromagnet. We have discovered a one-to-one mapping of the ferroelectric and ferromagnetic domains, mediated by the colinear coupling between the magnetization in the ferromagnet and the projection of the antiferromagnetic order in the multiferroic. Our preliminary experiments reveal the possibility to locally control ferromagnetism with an electric field.
View details for DOI 10.1038/nmat2184
View details for Web of Science ID 000256110200022
View details for PubMedID 18438412
- High-moment antiferromagnetic nanoparticles with tunable magnetic properties ADVANCED MATERIALS 2008; 20 (8): 1479-?
- Effects of geometries on permeability spectra of CoTaZr magnetic cores for high frequency applications 52nd Annual Conference on Magnetism and Magnetic Materials AMER INST PHYSICS. 2008
- Inductively coupled circuits with spin wave bus for information processing JOURNAL OF NANOELECTRONICS AND OPTOELECTRONICS 2008; 3 (1): 24-34
- The basin-range system along the south segment of the Karakorum fault zone, Tibet INTERNATIONAL GEOLOGY REVIEW 2008; 50 (2): 121-134
- GaN-based two-dimensional surface-emitting photonic crystal lasers with AlN/GaN distributed Bragg reflector APPLIED PHYSICS LETTERS 2008; 92 (1)
Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent.
2008; 19 (16): 165101
The purpose of this study was to synthesize biocompatible polyvinylpyrrolidone (PVP)-coated iron oxide (PVP-IO) nanoparticles and to evaluate their efficacy as a magnetic resonance imaging (MRI) contrast agent. The PVP-IO nanoparticles were synthesized by a thermal decomposition method and characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and a superconducting quantum interface device (SQUID). The core size of the particles is about 8-10 nm and the overall size is around 20-30 nm. The measured r(2) (reciprocal of T(2) relaxation time) and r2∗ (reciprocal of T2∗ relaxation time) are 141.2 and 338.1 (s mM)(-1), respectively. The particles are highly soluble and stable in various buffers and in serum. The macrophage uptake of PVP-IO is comparable to that of Feridex as measured by a Prussian blue iron stain and phantom study. The signal intensity of a rabbit liver was effectively reduced after intravenous administration of PVP-IO. Therefore PVP-IO nanoparticles are potentially useful for T(2)-weighted MR imaging.
View details for DOI 10.1088/0957-4484/19/16/165101
View details for PubMedID 21394237
View details for PubMedCentralID PMC3050625
- The Bacillus subtilis RNA helicase YxiN is distended in solution BIOPHYSICAL JOURNAL 2008; 94 (1): L1-L3
- Preparation, structural and magnetic characterization of synthetic anti-ferromagnetic (SAF) nanoparticles PHILOSOPHICAL MAGAZINE 2008; 88 (36): 4225-4241
- DETECTING LORENTZ INVARIANCE VIOLATIONS IN THE 10(-20) RANGE INTERNATIONAL JOURNAL OF MODERN PHYSICS D 2007; 16 (12B): 2393-2398
Strength of coronal mass ejection-driven shocks near the sun and their importance in predicting solar energetic particle events
2007; 670 (1): 849-856
View details for Web of Science ID 000250965400066
Genetic variation and population structure in Native Americans
2007; 3 (11): 2049-2067
We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.
View details for DOI 10.1371/journal.pgen.0030185
View details for Web of Science ID 000251310200002
View details for PubMedID 18039031
Interleukin-8 modulates growth and invasiveness of estrogen receptor-negative breast cancer cells
INTERNATIONAL JOURNAL OF CANCER
2007; 121 (9): 1949-1957
Breast cancer, especially estrogen receptor (ER)-negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER-negative breast cancers express high levels of interleukin-8 (IL-8), whereas their ER-positive counterparts do not. IL-8 is a multi-functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL-8 in ER-negative breast cancer progression by using RNA interference to specifically knockdown IL-8 expression in ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468. In vitro, suppression of IL-8 led to significant reductions in cell invasion (p<0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL-8 significantly reduced the microvessel density (p<0.05), and markedly reduced neutrophil infiltration into the tumors (p<0.05). In contrast to in vitro observations, suppression of IL-8 promoted tumor growth in nude mice (p<0.05). Our results imply that the complex roles of IL-8 in the regulation of ER-negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL-8.
View details for DOI 10.1002/ijc.22930
View details for Web of Science ID 000249718100009
View details for PubMedID 17621625
- Room temperature exchange bias and spin valves based on BiFeO3/SrRuO3/SrTiO3/Si (001) heterostructures APPLIED PHYSICS LETTERS 2007; 91 (17)
CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells
2007; 3 (9): 1757-1769
Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Global patterns of hypermethylation are tumor-type specific and nonrandom. The biological significance and the underlying mechanisms of tumor-specific aberrant promoter methylation remain unclear, but some evidence suggests that this specificity involves differential sequence susceptibilities, the targeting of DNA methylation activity to specific promoter sequences, or the selection of rare DNA methylation events during disease progression. Using restriction landmark genomic scanning on samples derived from tissue culture and in vivo models of T cell lymphomas, we found that MYC overexpression gave rise to a specific signature of CpG island hypermethylation. This signature reflected gene transcription profiles and was detected only in advanced stages of disease. The further inactivation of the Pten, p53, and E2f2 tumor suppressors in MYC-induced lymphomas resulted in distinct and diagnostic CpG island methylation signatures. Our data suggest that tumor-specific DNA methylation in lymphomas arises as a result of the selection of rare DNA methylation events during the course of tumor development. This selection appears to be driven by the genetic configuration of tumor cells, providing experimental evidence for a causal role of DNA hypermethylation in tumor progression and an explanation for the tremendous epigenetic heterogeneity observed in the evolution of human cancers. The ability to predict genome-wide epigenetic silencing based on relatively few genetic alterations will allow for a more complete classification of tumors and understanding of tumor cell biology.
View details for DOI 10.1371/journal.pgen.0030167
View details for Web of Science ID 000249767800018
View details for PubMedID 17907813
- Patterning of high density magnetic nanodot arrays by nanoimprint lithography 53rd International Symposium of the American-Vacuum-Society A V S AMER INST PHYSICS. 2007: 1294–97
- Time-varying MIMO channels: Parametric statistical Modeling and experimental results 6th IEEE Workshop on Signal Processing Advances in Wireless Communications IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2007: 1949–63
- Tensor nature of permeability and its effects in inductive magnetic devices 10th Joint Magnetism and Magnetic Materials Conference/International Magnetics Conference IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2007: 2373–75
- Analytical formula for the tunneling current versus voltage for multilayer barrier structures AMER INST PHYSICS. 2007
Branch migration displacement assay with automated heuristic analysis for discrete DNA length measurement using DNA microarrays
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2007; 104 (15): 6146-6151
The analysis of short tandem repeats (STRs) plays an important role in forensic science, human identification, genetic mapping, and disease diagnostics. Traditional STR analysis utilizes gel- or column-based approaches to analyze DNA repeats. Individual STR alleles are separated and distinguished according to fragment length; thus the assay is generally hampered by its low multiplex capacity. However, use of DNA microarray would employ a simple hybridization and detection for field forensics and biology. Here we demonstrate a rapid, highly sensitive method for STR analysis that utilizes DNA microarray technology. We describe two adaptations to accomplish this: the use of competitive hybridization to remove unpaired ssDNA from an array and the use of neural network classification to automate the analysis. The competitive displacement technique mimics the branch migration process that occurs during DNA recombination. Our technique will facilitate the rapid deduction of identity, length, and number of repeats for the multiple STRs in an unknown DNA sample.
View details for DOI 10.1073/pnas.0700921104
View details for Web of Science ID 000245737500012
View details for PubMedID 17389407
A novel method for STR-based DNA profiling using microarrays
JOURNAL OF FORENSIC SCIENCES
2005; 50 (5): 1109-1113
We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.
View details for Web of Science ID 000231660300013
View details for PubMedID 16225215
- Calculation of shape anisotropy for micropatterned thin Fe-Ni films for on-chip RF applications 9th Joint Magnetism and Magnetic Materials Conference/ International Magnetics Conference IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2004: 2835–37
Soft a-CoZr-based spin valves
AMER INST PHYSICS. 1997: 4007–
View details for Web of Science ID A1997WV53600102