Digital Commons Network^™

Optimal Aggregation Of Fcεri With A Structurally Defined Trivalent Ligand Overrides Negative Regulation Driven By Phosphatases, Avanika Mahajan, Dipak Barua, Patrick Cutler, Diane S. Lidke, Flor A. Espinoza, Carolyn Pehlke, Rachel Grattan, Yuko Kawakami, Chang-Shung Tung, Andrew R. M. Bradbury, William S. Hlavacek, Bridget S. Wilson

Chemical and Biochemical Engineering Faculty Research & Creative Works

To investigate why responses of mast cells to antigen-induced IgE receptor (FcεRI) aggregation depend nonlinearly on antigen dose, we characterized a new artificial ligand, DF3, through complementary modeling and experimentation. This ligand is a stable trimer of peptides derived from bacteriophage T4 fibritin, each conjugated to a hapten (DNP). We found low and high doses of DF3 at which degranulation of mast cells sensitized with DNP-specific IgE is minimal, but ligand-induced receptor aggregation is comparable to aggregation at an intermediate dose, optimal for degranulation. This finding makes DF3 an ideal reagent for studying the balance of negative and positive signaling …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Genetic Risk Of Progression To Type 2 Diabetes And Response To Intensive Lifestyle Or Metformin In Prediabetic Women With And Without A History Of Gestational Diabetes Mellitus., Shannon D Sullivan, Kathleen A. Jablonski, Jose C Florez, Dana Dabelea, Paul W Franks, Sam Dagogo-Jack, Catherine Kim, William C Knowler, Costas A Christophi, Robert Ratner, Diabetes Prevention Program Research Group.

GW Biostatistics Center

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Influence Of The X-Chromosome On Neuroanatomy: Evidence From Turner And Klinefelter Syndromes., David S Hong, Fumiko Hoeft, Matthew J Marzelli, Jean-Francois Lepage, David Roeltgen, Judith L. Ross, Allan L Reiss

Department of Psychiatry and Human Behavior Faculty Papers

Studies of sex effects on neurodevelopment have traditionally focused on animal models investigating hormonal influences on brain anatomy. However, more recent evidence suggests that sex chromosomes may also have direct upstream effects that act independently of hormones. Sex chromosome aneuploidies provide ideal models to examine this framework in humans, including Turner syndrome (TS), where females are missing one X-chromosome (45X), and Klinefelter syndrome (KS), where males have an additional X-chromosome (47XXY). As these disorders essentially represent copy number variants of the sex chromosomes, investigation of brain structure across these disorders allows us to determine whether sex chromosome gene dosage effects …

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

Attention, Predictive Learning, And The Inverse Base-Rate Effect: Evidence From Event-Related Potentials., Andy J. Wills, Aureliu Lavric, Yvonne Hemmings, Ed Surrey

School of Psychology

We report the first electrophysiological investigation of the inverse base-rate effect (IBRE), a robust non-rational bias in predictive learning. In the IBRE, participants learn that one pair of symptoms (AB) predicts a frequently occurring disease, whilst an overlapping pair of symptoms (AC) predicts a rarely occurring disease. Participants subsequently infer that BC predicts the rare disease, a non-rational decision made in opposition to the underlying base rates of the two diseases. Error-driven attention theories of learning state that the IBRE occurs because C attracts more attention than B. On the basis of this account we predicted and observed the occurrence …

Predicting The Risk Of Suicide By Analyzing The Text Of Clinical Notes, Chris Poulin, Brian Shiner, Paul Thompson, Linas Vepstas, Yinong Young-Xu, Benjamin Goertzel, Bradley Watts, Laura Flashman, Thomas Mcallister

Dartmouth Scholarship

We developed linguistics-driven prediction models to estimate the risk of suicide. These models were generated from unstructured clinical notes taken from a national sample of U.S. Veterans Administration (VA) medical records. We created three matched cohorts: veterans who committed suicide, veterans who used mental health services and did not commit suicide, and veterans who did not use mental health services and did not commit suicide during the observation period (n = 70 in each group). From the clinical notes, we generated datasets of single keywords and multi-word phrases, and constructed prediction models using a machine-learning algorithm based on a …

Identification Of A Developmental Gene Expression Signature, Including Hox Genes, For The Normal Human Colonic Crypt Stem Cell Niche: Overexpression Of The Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis., Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven E. Mckenzie, Jeremy Z Fields, Bruce M Boman

Kimmel Cancer Center Faculty Papers

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, …

Relationship Between Altitude And Lithium In Groundwater In The United States Of America: Results Of A 1992–2003 Study, Rebekah S. Huber, Namkug Kim, Carl E. Renshaw, Perry F. Renshaw, Douglas Kondo

Dartmouth Scholarship

Therapeutic dosages of lithium are known to reduce suicide rates, which has led to investigations of confounding environmental risk factors for suicide such as lithium in groundwater. It has been speculated that this might play a role in the potential relationship between suicide and altitude. A recent study in Austria involving geospatial analysis of lithium in groundwater and suicide found lower levels of lithium at higher altitudes. Since there is no reason to suspect this correlation is universal given variation in geology, the current study set out to investigate the relationship between altitude and lithium in groundwater in the United …

Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers …

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

Primary Microrna Processing Assay Reconstituted Using Recombinant Drosha And Dgcr8., Ian Barr, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

In animals, the Microprocessor complex cleaves primary transcripts of microRNAs (pri-miRNAs) to produce precursor microRNAs in the nucleus. The core components of Microprocessor include the Drosha ribonuclease and its RNA-binding partner protein DiGeorge critical region 8 (DGCR8). DGCR8 has been shown to tightly bind an Fe(III) heme cofactor, which activates its pri-miRNA processing activity. Here we describe how to reconstitute pri-miRNA processing using recombinant human Drosha and DGCR8 proteins. In particular, we present the procedures for expressing and purifying DGCR8 as an Fe(III) heme-bound dimer, the most active form of this protein, and for estimating its heme content.

A Simplified Score To Quantify Comorbidity In Copd, Nirupama Putcha, Milo A. Puhan, M. Bradley Drummond, Meilan K. Han, Elizabeth A. Regan, Nicola A. Hanania, Carlos H. Martinez, Marilyn Foreman, Surya P. Bhatt, Barry Make, Joe Ramsdell, Dawn L. Demeo, R. Graham Barr, Stephen I. Rennard, Fernando Martinez, Edwin K. Silverman, James Crapo, Robert A. Wise, Nadia N. Hansel

Journal Articles: Pulmonary & Critical Care Med

IMPORTANCE: Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

MATERIALS AND METHODS: Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes …

Overexpression Of Dcf1 Inhibits Glioma Through Destruction Of Mitochondria And Activation Of Apoptosis Pathway, Yuqiong Xie, Qang Li, Qingbo Yang

Electrical and Computer Engineering Faculty Research & Creative Works

Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To …

Empirical Models Of Scalp-Eeg Responses Using Non-Concurrent Intracranial Responses, Komalpreet Kaur, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

Objective- This study presents inter-subject models of scalp-recorded electroencephalographic (sEEG) event-related potentials (ERPs) using intracranially recorded ERPs from electrocorticography and stereotactic depth electrodes in the hippocampus, generally termed as intracranial EEG (iEEG).

Approach- The participants were six patients with medically-intractable epilepsy that underwent temporary placement of intracranial electrode arrays to localize seizure foci. Participants performed one experimental session using a brain-computer interface matrix spelling paradigm controlled by sEEG prior to the iEEG electrode implantation, and one or more identical sessions controlled by iEEG after implantation. All participants were able to achieve excellent spelling accuracy using sEEG, four of the participants …

A Proto-Architecture For Innate Directionally Selective Visual Maps., Sv Adams, Cm Harris

School of Psychology

Self-organizing artificial neural networks are a popular tool for studying visual system development, in particular the cortical feature maps present in real systems that represent properties such as ocular dominance (OD), orientation-selectivity (OR) and direction selectivity (DS). They are also potentially useful in artificial systems, for example robotics, where the ability to extract and learn features from the environment in an unsupervised way is important. In this computational study we explore a DS map that is already latent in a simple artificial network. This latent selectivity arises purely from the cortical architecture without any explicit coding for DS and prior …

Patient-Centered Appointment Scheduling Using Agent-Based Simulation., Ayten Turkcan, Tammy Toscos Phd, Brad N Doebbeling

Health Services and Informatics Research

Enhanced access and continuity are key components of patient-centered care. Existing studies show that several interventions such as providing same day appointments, walk-in services, after-hours care, and group appointments, have been used to redesign the healthcare systems for improved access to primary care. However, an intervention focusing on a single component of care delivery (i.e. improving access to acute care) might have a negative impact other components of the system (i.e. reduced continuity of care for chronic patients). Therefore, primary care clinics should consider implementing multiple interventions tailored for their patient population needs. We collected rapid ethnography and observations to …

Thinking In Circuits: Toward Neurobiological Explanation In Cognitive Neuroscience., Friedemann Pulvermüller, Max Garagnani, Thomas Wennekers

School of Engineering, Computing and Mathematics

Cognitive theory has decomposed human mental abilities into cognitive (sub) systems, and cognitive neuroscience succeeded in disclosing a host of relationships between cognitive systems and specific structures of the human brain. However, an explanation of why specific functions are located in specific brain loci had still been missing, along with a neurobiological model that makes concrete the neuronal circuits that carry thoughts and meaning. Brain theory, in particular the Hebb-inspired neurocybernetic proposals by Braitenberg, now offers an avenue toward explaining brain-mind relationships and to spell out cognition in terms of neuron circuits in a neuromechanistic sense. Central to this endeavor …

Learning To Pronounce First Words In Three Languages: An Investigation Of Caregiver And Infant Behavior Using A Computational Model Of An Infant., Ian S. Howard, Piers Messum

School of Engineering, Computing and Mathematics

Words are made up of speech sounds. Almost all accounts of child speech development assume that children learn the pronunciation of first language (L1) speech sounds by imitation, most claiming that the child performs some kind of auditory matching to the elements of ambient speech. However, there is evidence to support an alternative account and we investigate the non-imitative child behavior and well-attested caregiver behavior that this account posits using Elija, a computational model of an infant. Through unsupervised active learning, Elija began by discovering motor patterns, which produced sounds. In separate interaction experiments, native speakers of English, French and …

Pax Genes: Regulators Of Lineage Specification And Progenitor Cell Maintenance, Judith A. Blake, Mel R. Ziman

Research outputs 2014 to 2021

Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We …

Specific Intracellular Uptake Of Herceptin-Conjugated Cdse/Zns Quantum Dots Into Breast Cancer Cells, Seung-Jin Han, Pierson Rathinaraj, Soo-Young Park, Young-Kyoo Kim, Joon Hyung Lee, Inn-Kyu Kang, Jong-Sik Moon, Jeffrey G. Winiarz

Chemistry Faculty Research & Creative Works

Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). the mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. the in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. to clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined …

A Comparison Of Aphasia Therapy Outcomes Before And After A Very Early Rehabilitation Programme Following Stroke, Erin Godecke, Natalie A. Ciccone, Andrew S. Granger, Tapan Rai, Deborah West, Angela Cream, Jade Cartwright, Graeme J. Hankey

Research outputs 2014 to 2021

Background Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke) and again at follow-up (6 months). Methods & Procedures This study compared two cohorts from successive studies conducted in four Australian acute/sub-acute hospitals. The studies had near identical recruitment, blinded assessment and data-collection protocols. The Very Early Rehabilitation (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions …

Benthic And Pelagic Pathways Of Methylmercury Bioaccumulation In Estuarine Food Webs Of The Northeast United States, Celia Y. Chen, Mark E. Borsuk, Deenie M. Bugge, Terill Hollweg

Dartmouth Scholarship

Methylmercury (MeHg) is a contaminant of global concern that bioaccumulates and bioamagnifies in marine food webs. Lower trophic level fauna are important conduits of MeHg from sediment and water to estuarine and coastal fish harvested for human consumption. However, the sources and pathways of MeHg to these coastal fisheries are poorly known particularly the potential for transfer of MeHg from the sediment to biotic compartments. Across a broad gradient of human land impacts, we analyzed MeHg concentrations in food webs at ten estuarine sites in the Northeast US (from the Hackensack Meadowlands, NJ to the Gulf of Maine). MeHg concentrations …

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …

Identifying Potential Cancer Driver Genes By Genomic Data Integration., Yong Chen, Jingjing Hao, Wei Jiang, Tong He, Xuegong Zhang, Tao Jiang, Rui Jiang

College of Science & Mathematics Departmental Research

Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …