gebhart/patrepeval huggingface dataset:
Nanotextured superhydrophobic electrodes enable detection of attomolar-scale DNA concentration within a droplet by non-faradaic impedance spectroscopy (2013)

Label-free, rapid detection of biomolecules in microliter volumes of highly diluted solutions (sub-femtomolar) is of essential importance for numerous applications in medical diagnostics, food safety, and chem-bio sensing for homeland security. At ultra-low concentrations, regardless of the sensitivity of the detection approach, the sensor response time is limited by physical diffusion of molecules towards the sensor surface. We have developed a fast, low cost, non-faradaic impedance sensing method for detection of synthetic DNA molecules in DI water at attomolar levels by beating the diffusion limit through evaporation of a micro-liter droplet of DNA on a nanotextured superhydrophobic electrode array. Continuous monitoring of the impedance of individual droplets as a function of evaporation time is exploited to dramatically improve the sensitivity and robustness of detection. Formation of the nanostructures on the electrode surface not only increases the surface hydrophobicity, but also allows robust pinning of the droplet contact area to the sensor surface. These two features are critical for performing highly stable impedance measurements as the droplet evaporates. Using this scheme, the detection limit of conventional non-faradaic methods is improved by five orders of magnitude. The proposed platform represents a step-forward towards realization of ultra-sensitive lab-on-chip biomolecule detectors for real time point-of-care application. Further works are however needed to ultimately realize the full potential of the proposed approach to appraise biological samples in complex buffer solutions rather than in DI water.
Regulation of endothelial and hematopoietic development by the ETS transcription factor Etv2 (2012)

Etv2 is essential for the specification of endothelial and hematopoietic lineages. Understanding the mechanisms through which Etv2 specifies endothelial and blood cells by defining upstream transcriptional regulators and cofactors will lead to greater insight into vasculogenesis and hematopoiesis, and may help to identify therapeutic targets to treat vascular disorders or to promote or inhibit vessel growth.
Developments in Luminescence and Display Materials Over the Last 100 Years as Reflected in Electrochemical Society Publications (2002)

NRC publication: Yes
Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors (2015)

Small-molecule inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, and BRD4 proteins have therapeutic potential for the treatment of human cancers and other diseases and conditions. In this paper, we report the design, synthesis, and evaluation of γ-carboline-containing compounds as a new class of small-molecule BET inhibitors. The most potent inhibitor (compound 18, RX-37) obtained from this study binds to BET bromodomain proteins (BRD2, BRD3, and BRD4) with Ki values of 3.2-24.7 nM and demonstrates high selectivity over other non-BET bromodomain-containing proteins. Compound 18 potently and selectively inhibits cell growth in human acute leukemia cell lines harboring the rearranged mixed lineage leukemia 1 gene. We have determined a cocrystal structure of 18 in complex with BRD4 BD2 at 1.4 Å resolution, which provides a solid structural basis for the compound's high binding affinity and for its further structure-based optimization. Compound 18 represents a promising lead compound for the development of a new class of therapeutics for the treatment of human cancer and other conditions.
Cellular Production of n-3 PUFAs and Reduction of n-6–to–n-3 Ratios in the Pancreatic β-Cells and Islets Enhance Insulin Secretion and Confer Protection Against Cytokine-Induced Cell Death (2009)

Stable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced beta-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo.
Error analysis of background adaption (2002)

Background modeling is a common component in video surveillance systems and is used to quickly identify regions of interest. To increase the robustness of background subtraction techniques, researchers have developed techniques to update the background model and also developed probabilistic/statistical approaches for thresholding the difference. This paper presents an error analysis of this type of background modeling and pixel labeling, providing both theoretical analysis and experimental validation. Evaluation is centered around the tradeoff of probability of false alarm and probability of miss detection, and this paper shows how to efficiently compute these probabilities front simpler values that are more easily measured. It includes an analysis for both static and dynamic background modeling. The paper also examines the assumptions of Gaussian and mixture of Gaussian models for a pixel.
Animal Models of Zika Virus Infection, Pathogenesis, and Immunity (2017)

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.
Bioisosteres in medicinal chemistry (2012)

Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism. As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development. The first part provides an overview of bioisosterism, classical bioisosteres and typical molecular interactions that need to be considered, while the second part describes a number of molecular databases as sources of bioisosteric identification and rationalization. The third part covers the four key methodologi
Regulation of the Cell Expansion Gene RHD3 during Arabidopsis Development (2002)

The RHD3 (ROOT HAIR DEFECTIVE3) gene encodes a putative GTP-binding protein required for appropriate cell enlargement in Arabidopsis. To obtain insight into the mechanisms of RHD3 regulation, we conducted a molecular genetic dissection of RHD3 gene expression and function. Gene fusion and complementation studies show that the RHD3 gene is highly expressed throughout Arabidopsis development and is controlled by two major regulatory regions. One regulatory region is located between -1,500 and -600 bp upstream of the RHD3 gene and is required for vascular tissue expression. The other region is intragenically located and includes the 558-bp first intron, which is responsible for high-level expression of RHD3 throughout the plant. The presence and location of this intron is essential for gene function because constructs lacking this intron or constructs with the intron in an abnormal position are unable to functionally complement the rhd3 mutations. We also analyzed the role of other RHD genes and the plant hormones auxin and ethylene in RHD3 regulation, and we determined that these act downstream or independently from the RHD3 pathway. This study shows that multiple levels of regulation are employed to ensure the appropriate expression of RHD3 throughout Arabidopsis development.
Bezel swipe (2009)

Zooming user interfaces are increasingly popular on mobile devices with touch screens. Swiping and pinching finger gestures anywhere on the screen manipulate the displayed portion of a page, and taps open objects within the page. This makes navigation easy but limits other manipulations of objects that would be supported naturally by the same gestures, notably cut and paste, multiple selection, and drag and drop. A popular device that suffers from this limitation is Apple's iPhone. In this paper, we present Bezel Swipe, an interaction technique that supports multiple selection, cut, copy, paste and other operations without interfering with zooming, panning, tapping and other pre-defined gestures. Participants of our user study found Bezel Swipe to be a viable alternative to direct touch selection.
Water-Soluble Single-Walled Carbon Nanotubes via Noncovalent Sidewall-Functionalization with a Pyrene-Carrying Ammonium Ion (2002)

Abstract In this communication, we describe the finding that sonication of solid single-walled carbon nanotubes (p-SWNT) in an aqueous solution of a pyrene-carrying ammonium ion 1 gave a transparent dispersion/solution of the nanotubes, which was characterized by transmission electron microscopy, UV-vis absorption, fluorescence and 1H NMR spectroscopies. We showed evidence for the interaction of the nanotube sidewall and the pyrene moiety in the aqueous dispersion/solution.
Vascular Endothelial Growth Factor Mediates Intracrine Survival in Human Breast Carcinoma Cells through Internally Expressed VEGFR1/FLT1 (2007)

This study provides, to our knowledge for the first time, evidence of a unique survival system in breast cancer cells by which VEGF can act as an internal autocrine (intracrine) survival factor through its binding to VEGFR1. These results may lead to an improved strategy for tumor therapy based on the inhibition of angiogenesis.
High‐throughput multiplex single‐nucleotide polymorphism analysis for red cell and platelet antigen genotypes (2005)

The platform has the capacity to genotype thousands of samples per day. The suite of SNPs provides genotype data for all blood donors within 36 hours of the start of testing.
Defining the clinical course of multiple sclerosis (1996)

Standardization of terminology used to describe the pattern and course of MS is essential for mutual understanding between clinicians and investigators. It is particularly important in design of, and recruitment for, clinical trials statistically powered for expected outcomes for given patient populations with narrowly defined entry criteria. For agents that prove safe and effective for MS, knowledge of the patient populations in definitive clinical trials assists clinicians in determining who may ultimately benefit from use of the medication. An international survey of clinicians involved with MS revealed areas of consensus about some terms classically used to describe types of the disease and other areas for which there was lack of consensus. In this report, we provide a summary of the survey results and propose standardized definitions for the most common clinical courses of patients with MS.
Isolation and characterization of a cell surface albumin-binding protein from vascular endothelial cells. (1996)

Albumin-binding proteins identified in vascular endothelial cells have been postulated to contribute to the transport of albumin via a process involving transcytosis. In the present study, we have purified and characterized a 57- to 60-kDa (gp60) putative albumin-binding protein from bovine pulmonary microvessel endothelial cells. The endothelial cell membranes were isolated from cultured cells by differential centrifugation and solubilized with sodium cholate and urea. The solubilized extract was concentrated after dialysis by ethanol precipitation and reextracted with Triton X-100, and the resulting extract was subjected to DEAE-cellulose column chromatography. Proteins eluted from this column were further separated using preparative sodium dodecyl sulfate/polyacrylamide gel electrophoresis and used for immunizing rabbits. Fluorescence-activated cell sorter analysis using the anti-gp60 antibodies demonstrated the expression of gp60 on the endothelial cell surface. Affinity-purified anti-gp60 antibodies inhibited approximately 90% of the specific binding of 125I-labeled albumin to bovine pulmonary microvessel endothelial cell surface. The anti-gp60 antibodies reacted with gp60 from bovine pulmonary artery, bovine pulmonary microvessel, human umbilical vein, and rat lung endothelial cell membranes. Bovine anti-gp60 antibodies also reacted with bovine secreted protein, acidic and rich in cysteine (SPARC). However, bovine SPARC NH2-terminal sequence (1-56 residues) antibodies did not react with gp60, indicating that the endothelial cell-surface-associated albumin-binding protein gp60 was different from the secreted albumin-binding protein SPARC. We conclude that the endothelial cell-surface-associated gp60 mediates the specific binding of native albumin to endothelial cells and thus may regulate the uptake of albumin and its transcytosis.
Generalized Lagrange Multiplier Method for Solving Problems of Optimum Allocation of Resources (1963)

The usefulness of Lagrange multipliers for optimization in the presence of constraints is not limited to differentiable functions. They can be applied to problems of maximizing an arbitrary real valued objective function over any set whatever, subject to bounds on the values of any other finite collection of real valued functions denned on the same set. While the use of the Lagrange multipliers does not guarantee that a solution will necessarily be found for all problems, it is “fail-safe” in the sense that any solution found by their use is a true solution. Since the method is so simple compared to other available methods it is often worth trying first, and succeeds in a surprising fraction of cases. They are particularly well suited to the solution of problems of allocating limited resources among a set of independent activities.
Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. (1993)

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (FUra), one of the most widely used anticancer drugs. Previous studies from our laboratory demonstrated the clinical importance of DPD in cancer patients (G. D. Heggie, J-P. Sommadossi, D. S. Cross, W. J. Huster, and R. B. Diasio. Cancer Res., 47: 2203-2206, 1987; B. E. Harris, R. Song, S-j. Soong, and R. B. Diasio. Cancer Res., 50: 197-201, 1990), particularly in those with DPD deficiency who experience severe FUra toxicity (including death) following FUra treatment [R. B. Diasio, T. L. Beavers, and J. T. Carpenter. J. Clin. Invest., 81: 47-51, 1988; B. E. Harris, J. T. Carpenter, and R. B. Diasio. Cancer (Phila.), 68: 499-501, 1991]. We now suggest that measurement of DPD activity may be useful in routine screening of cancer patients prior to FUra treatment. In this paper, we describe the following serial studies: (a) we developed a sensitive, accurate, and precise DPD assay and a storage method to stabilize DPD activity, permitting large scale DPD screening in cancer patients; (b) we demonstrated a normal distribution (Gaussian distribution) of human DPD activity from peripheral blood mononuclear cells (PBM-DPD) in a population study. Baselines for PBM-DPD with fresh and frozen samples were 0.425 +/- 0.124 (SD) and 0.189 +/- 0.064 nmol/min/mg protein, respectively. The 95% and 99% distribution ranges for both fresh and frozen samples were also determined, providing criteria for detection of DPD-deficient patients; (c) we identified nine new patients with profound or partial DPD deficiency; (d) we determined a baseline for human liver DPD activity, which was shown to be 0.360 +/- 0.182 nmol/min/mg protein (frozen samples); (e) we did a preliminary evaluation of liver DPD from deficient patients. Low liver DPD activity in two deficient patients correlated with low PBM-DPD activity. Using a polyclonal antibody raised against human liver DPD in our laboratory (Z. Lu, R. Zhang, and R. B. Diasio. J. Biol. Chem., 267: 17102-17109, 1992), Western blot analysis demonstrated decreased DPD protein in the liver cytosol from DPD-deficient patients compared to normal subjects. These results may be useful in improving the effectiveness and/or lessening the toxicity of FUra chemotherapy.
Improvements in the Diagnostic Approach for Patients with Suspected Deep Vein Thrombosis or Pulmonary Embolism (1999)

Recent advances in the management of patients with suspected VTE have resulted in improvements in the diagnostic testing accuracy and the development of management algorithms that are safer and more accessible. Ongoing clinical trials are evaluating whether these diagnostic management strategies can be made even simpler and less expensive. Diagnostic procedures for VTE continue to be refined, and modalities, such as magnetic resonance imaging and spiral CT, have the potential to further increase the accuracy of the investigation approach. There is still need to improve management strategies for the diagnosis of recurrent venous thrombosis and to determine whether diagnostic testing results may be correlated with long-term patient treatment needs.
The usefulness of oligoclonal bands in cerebrospinal fluids for diagnosis in multiple sclerosis. (2000)

髄液のオリゴクローナルバンド (OCB) を検出するため, アガロース電気泳動とイムノブロッティングを組み合わせた, 簡便で感度のよい方法を工夫した. 本法では髄液を濃縮する必要がない. 髄液のような低濃度の蛋白の分離に効果的であり, 特異性に優れている. 私達は髄液のIgGが低濃度の例や, 髄液のIgGが高濃度でポリクローナルのIgGのスメアにマスクされるような例でも, 髄液のOCBを明瞭に検出できた. 私達の方法は髄液のOCBの同定に有用である.
Genome‐wide analysis of the unfolded protein response in fibroblasts from congenital disorders of glycosylation type‐I patients (2004)

Congenital disorders of glycosylation (CDG) are a family of diseases characterized by defects of N-linked glycosylation. In CDG-I, several genetic defects cause a shortage of dolichol-linked oligosaccharides, which leads to underglycosylation of nascent glycoproteins. N-linked glycosylation is important for proper folding and trafficking of glycoproteins. Inhibition of glycosylation results in the buildup of misfolded proteins in the endoplasmic reticulum, which induces a protective reaction known as the unfolded protein response (UPR). To investigate whether UPR components are induced in CDG, we have performed a transcriptome analysis of primary fibroblasts from unaffected control subjects and from CDG-I patients using oligonucleotide gene expression arrays. The stress imposed by CDG was also compared with the stress induced by tunicamycin and glucose deprivation. Whereas tunicamycin elicited a strong transcriptional response typical for the UPR, CDG fibroblasts displayed a qualitatively similar yet moderate induction of genes encoding components of the UPR. Among these genes, the PERK kinase inhibitor DNAJC3/P58(IPK) gene showed the highest induction throughout all CDG-I types tested. This was paralleled by elevated expression of genes involved in amino acid biosynthesis and transport, which defined a new component of the cellular response to glycosylation stress.
Diverse effects of zinc on NF- B and AP-1 transcription factors: implications for prostate cancer progression (2006)

Nuclear factor-kappaB (NF-kappaB) and AP-1 nuclear transcriptional factors regulate expression of multiple genes involved in tumor growth, metastasis and angiogenesis; however, the relative contribution of each factor to cancer initiation and progression has not been established. Prostate carcinogenesis involves transformation of normal zinc-accumulating epithelial cells to malignant cells that do not accumulate zinc. Whereas activation of both NF-kappaB and AP-1 has been implicated in prostate cancer development and growth, we tested the relative effects of zinc supplementation on these important transcriptional factors. Herein, we demonstrate that physiological levels of zinc inhibit NF-kappaB but augment activities of AP-1 in DU-145 and PC-3 human prostate cancer cells. Additionally, we show that chelation of zinc with membrane-permeable zinc chelator, N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) abolishes this effect. We further propose a potential mechanism for this observation by demonstrating that zinc supplementation induces phosphorylation of the members of three major MAPK subfamilies regulating AP-1 and NF-kappaB activation (ERK 1/2, JNK and p38) while blocking TNF-alpha-mediated degradation of the inhibitory subunit I kappa B alpha and nuclear translocation of RelA in prostate cancer cells. VEGF, IL-6, IL-8 and MMP-9 are major pro-angiogenic and pro-metastatic molecules whose promoter regions contain binding sites for both NF-kappaB and AP-1. These cytokines have been associated with negative prognostic features in prostate cancer. We demonstrate that treatment of human prostate cancer cell lines with zinc reduces expression of VEGF, IL-6, IL-8 and MMP-9. We further show that zinc reduces expression of intercellular adhesion molecule-1 and functionally suppresses tumor cell invasiveness and adhesion. Therefore, the ability of zinc supplementation to inhibit NF-kappaB supercedes zinc-mediated activation of AP-1 family members. Upregulation of intracellular zinc levels may have important implications for inhibiting the angiogenic and metastatic potentials of malignant cells, predominantly through suppression of NF-kappaB signaling.
Neuronal circuitry of thalamocortical epilepsy and mechanisms of antiabsence drug action. (1999)

Powerful mechanisms exist within the thalamus that lead to the promotion of synchronous and phasic 3 Hz neuronal activity. These mechanisms include robust burst-firing capability of thalamic neurons, recurrent excitatory and inhibitory synaptic connectivity, and long-lasting and powerful inhibitory synaptic responses arising from activity in thalamic reticular neurons and mediated by gamma-aminobutyric acid (GABA) receptors. The 3 Hz thalamic synchronization appears to arise from a perturbation of a physiologic, higher frequency spindle oscillation. Two currently available antiabsence medications interact with this circuitry with the net result of decreased synchronization, largely through reduction in inhibitory output from the thalamic reticular nucleus. Ethosuximide blocks T-type calcium channels and thus reduces the ability of thalamic neurons to fire bursts of spikes, thereby reducing inhibitory (and excitatory) output within the circuit. By contrast, clonazepam enhances recurrent inhibitory strength within the reticular nucleus. This results in a decreased ability of neighboring inhibitory neurons to fire synchronously and produce the powerful inhibitory synaptic responses that are required for network synchronization.