gebhart/patrepeval huggingface dataset:
Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in β cells (1999)

Previous investigations revealed low activities of lactate dehydrogenase (LDH) and plasma membrane monocarboxylate transporters (MCT) in the pancreatic beta cell. In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets. Inducible overexpression of LDH-A resulted in an 87-fold increase in LDH activity in INS-1 cells. Adenovirus-mediated overexpression of MCT-1 increased lactate transport activity 3.7-fold in INS-1 cells. Although overexpression of LDH-A, and/or MCT-1 did not affect glucose-stimulated insulin secretion, LDH-A overexpression resulted in stimulation of insulin secretion even at a low lactate concentration with a concomitant increase in its oxidation in INS-1 cells regardless of MCT-1 co-overexpression. Adenovirus-mediated overexpression of MCT-1 caused an increase in pyruvate oxidation and conferred pyruvate-stimulated insulin release to isolated rat islets. Although lactate did not stimulate insulin secretion from control or MCT-1-overexpressing islets, co-overexpression of LDH-A and MCT-1 evoked lactate-stimulated insulin secretion with a concomitant increase in lactate oxidation in rat islets. These results suggest that low expression of MCT and LDH is requisite to the specificity of glucose in insulin secretion, protecting the organism from undesired hypoglycemic actions of pyruvate and lactate during exercise and other catabolic states.
Evaluation of the Enterprise Point-of-Care (EPOC) System for Blood Gas and Electrolyte Analysis (2008)

Objective: To evaluate the analytical performance of a new point-of-care blood gas and electrolyte analyzer, the EPOC system. Materials and Methods: Evaluation of analytical precision and method comparison was conducted at the manufacturing facilities and at several locations in a 630-bed tertiary acute care ho in New England, an intensive care unit, cardiac intensive care unit, an out hematology/oncology clinic, and the Baystate Health system central laboratory (Springfield, Mass). The evaluation was conducted by nursing staff, medical laboratory technicians, medical technologists, and pathology residents. Results: Within-run precision (0.07%-2.3% coefficient of variation [CV]) and total precision (0.14%-3.8% CV) were estimated by analysis of aqueous and hematocrit control materials. A total of 143 samples leftover from laboratory analysis were compared with the predicate device, the i-STAT. One sample was excluded for potential benzalkonium interference with electrolytes, and another sample was excluded from the hematocrit correlation because of suspected incomplete mixing. The EPOC system was comparable to the i-STAT for all analytes with correlation coefficients of 0.880 to 0.990, linear regression slopes of 0.91 to 1.07, and SE of the estimates of 1.5% to 2.5% CV for electrolytes and pH, 3.9% for hematocrit, and 4.9% to 7.3% CV for blood gases. Conclusions: The EPOC system demonstrated excellent analytical precision and comparability of patient results to the i-STAT. The EPOC system has room temperature storage of test cards and wireless connectivity that provides an operational advantage over other point-of-care blood gas analyzers on the market.
Enzyme-Linked Immunosorbent Assay of Benomyl and Thiabendazole in Some Foods (1987)

Enzyme-linked immunosorbent assays were developed for benomyl as its decomposition product, methyl 2-benzimidazole carbamate, and thiabendazole in foods. Immunogens consisting of human serum albumin coupled to 2-succinamidobenzimidazole or 2-(2'-succinamido-4'-thiazolyl)benzimidazole were used in rabbits to raise antisera that were specific for the respective fungicides. Lower limits of quantitation of 0.35 ppm for benomyl and 0.03 ppm for thiabendazole were established without cleanup of the ethyl acetate extract. Recoveries of benomyl from 3 crops spiked at 0.5 to 10 ppm averaged 89% (range 73-109%) and of thiabendazole from 5 crops spiked at 0.1 to 2.0 ppm were 93% (range 81-105%).
A Router Architecture for Networks on Silicon (2001)

To deal with the increasing design complexity of integrated systems reuse of intellectual property (IP) blocks is promoted. A system architecture then becomes a composition of a heterogeneous set of such IP blocks together with a network that interconnects these blocks. The main challenge of system design therefore shifts from computation (IP blocks) to communication and storage (interconnect and memories). This means that applications become dynamic compositions of IP blocks which requires that the network is scalable (in the number of attached IP blocks), programmable and behaves predictably under the traffic offered by those blocks. As the feature size decreases the relative cost of wires increases. We therefore search for an interconnect network that efficiently uses wires through sharing by introducing routers. For a flexible and efficient solution at least two traffic classes must be support by the network, viz., guaranteedthroughput (GT) and best-effort (BE). For GT traffic communication channels are set up to transport data between IP blocks (possibly via memory). Best-effort traffic is never lost, but no latency or through-put guarantees are given. We also address the conflicting requirements of GT and BE traffic [1]. Our router is packet-switched and uses input-queuing with an efficient packet/flit scheduling [2] for BE traffic, whereas efficient time division multiplexing scheme is used is used for GT traffic. The focus of this paper is on the derivation of a costeffective router and network suitable for on-chip integration.
Epigenome characterization at single base-pair resolution (2011)

We have combined standard micrococcal nuclease (MNase) digestion of nuclei with a modified protocol for constructing paired-end DNA sequencing libraries to map both nucleosomes and subnucleosome-sized particles at single base-pair resolution throughout the budding yeast genome. We found that partially unwrapped nucleosomes and subnucleosome-sized particles can occupy the same position within a cell population, suggesting dynamic behavior. By varying the time of MNase digestion, we have been able to observe changes that reflect differential sensitivity of particles, including the eviction of nucleosomes. To characterize DNA-binding features of transcription factors, we plotted the length of each fragment versus its position in the genome, which defined the minimal protected region of each factor. This process led to the precise mapping of protected and exposed regions at and around binding sites, and also determination of the degree to which they are flanked by phased nucleosomes and subnucleosome-sized particles. Our protocol and mapping method provide a general strategy for epigenome characterization, including nucleosome phasing and dynamics, ATP-dependent nucleosome remodelers, and transcription factors, from a single-sequenced sample.
Deletions at the Carboxyl Terminus of Vaccinia DNA Topoisomerase Affect DNA Binding and Enhance Distributivity in DNA Relaxation (1997)

Vaccinia topoisomerase relaxes DNA through the formation of a covalent DNA-(3'-phosphotyrosyl)protein intermediate at sites containing the sequence 5'-(T/C)CCTT/. The active site, Tyr-274, is situated near the carboxyl terminus of the 314 amino acid enzyme. Here, we report the effects of serial C-terminal deletions. Removal of five amino acids had no effect on topoisomerase activity. However, deletion of 10, 15, or 20 amino acids rendered the enzyme distributive in DNA relaxation, incrementally slowed the rate of single-turnover DNA cleavage, and progressively diminished DNA binding affinity, without altering the sequence specificity of DNA cleavage. These effects lead us to speculate that the region downstream of the active site, which is not well-conserved among the poxvirus-encoded topoisomerases, is a component of the proposed circumferential interface between the enzyme and duplex DNA.
Corneal perforations. Changing methods of treatment, 1960--1980. (1982)

One hundred four nontraumatic corneal perforations or descemetoceles in patients admitted to the Wilmer Institute from 1960 to 1980 were studied retrospectively, with follow-up data obtained from records or from referral physicians for 87 of these perforations. Forty-nine percent of the cases were caused by bacterial corneal ulcers, 13% by exposure, 12% by chemical burns, 6% by fungal keratitis, 5% by herpes simplex keratitis, and 15% were undiagnosed. Since the start of tissue adhesive use at the Wilmer Institute in 1974, there has been an apparent trend towards a lower enucleation rate (6%) in corneal perforations treated with tissue adhesive as compared to 19% in perforations treated by other therapies, although the cases may not be entirely comparable. An improved visual result of 20/200 or better was achieved in 29% of patients treated with tissue adhesive as compared to 19% with other treatment.
The Regulation of Exosome Secretion: a Novel Function of the p53 Protein (2006)

The p53 protein responds to stress signals by regulating the transcription of a variety of genes. Some of these genes encode secreted proteins that may be involved in the communication between adjacent cells. In this study, a proteomics approach was employed to identify proteins secreted by cells in a p53-dependent manner after DNA damage. In addition to the known transcriptional targets of p53, a set of proteins encoded by genes that are not transcriptional targets of p53 were found to increase in the culture medium after p53 activation. These proteins exit the cell via small, secreted vesicles called exosomes and exosome production by cells was found to be regulated by the p53 response. A p53-regulated gene product, TSAP6, was shown to enhance exosome production in cells undergoing a p53 response to stress. Thus, the p53 pathway regulates the production of exosomes into the medium and these vesicles can communicate with adjacent cells and even cells of the immune system.
Interpretation of the electronic fetal heart rate during labor. (1999)

Electronic fetal heart rate monitoring is commonly used to assess fetal well-being during labor. Although detection of fetal compromise is one benefit of fetal monitoring, there are also risks, including false-positive tests that may result in unnecessary surgical intervention. Since variable and inconsistent interpretation of fetal heart rate tracings may affect management, a systematic approach to interpreting the patterns is important. The fetal heart rate undergoes constant and minute adjustments in response to the fetal environment and stimuli. Fetal heart rate patterns are classified as reassuring, nonreassuring or ominous. Nonreassuring patterns such as fetal tachycardia, bradycardia and late decelerations with good short-term variability require intervention to rule out fetal acidosis. Ominous patterns require emergency intrauterine fetal resuscitation and immediate delivery. Differentiating between a reassuring and nonreassuring fetal heart rate pattern is the essence of accurate interpretation, which is essential to guide appropriate triage decisions.
The boundary cap: a source of neural crest stem cells that generate multiple sensory neuron subtypes (2005)

The boundary cap (BC) is a transient neural crest-derived group of cells located at the dorsal root entry zone (DREZ) that have been shown to differentiate into sensory neurons and glia in vivo. We find that when placed in culture, BC cells self-renew, show multipotency in clonal cultures and express neural crest stem cell (NCSCs) markers. Unlike sciatic nerve NCSCs, the BC-NCSC (bNCSCs) generates sensory neurons upon differentiation. The bNCSCs constitute a common source of cells for functionally diverse types of neurons, as a single bNCSC can give rise to several types of nociceptive and thermoreceptive sensory neurons. Our data suggests that BC cells comprise a source of multipotent sensory specified stem cells that persist throughout embryogenesis.
An Inherited Variable Poly-T Repeat Genotype in TOMM40 in Alzheimer Disease (2010)

I coauthored a recently published research article describing a variable length, poly-T polymorphism in the TOMM40 gene, adjacent to apolipoprotein E (APOE) on chromosome 19, that accounts for the age at onset distribution for a complex disease, late-onset Alzheimer disease. These new data explain the mean age at disease onset for patients with the APOE4/4 genotype and differentiate 2 forms of TOMM40 poly-T polymorphisms linked to APOE, with each form associated with a different age at disease onset distribution. When linked to APOE3 (encoding the epsilon3 isoform of APOE), the longer TOMM40 poly-T repeats (19-39 nucleotides) at the rs10524523 (hereafter, 523) locus are associated with earlier age at onset and the shorter TOMM40 523 alleles (11-16 nucleotides) are associated with later age at onset. The data suggest that the poly-T alleles are codominant, with the age at onset phenotype determined by the 2 inherited 523 alleles, but with variable expressivity. Additional data will further refine the relationship between the length of the poly-T alleles and age at disease onset and determine if the relationship is linear.
Effects of the Ionic Environment, Charge, and Particle Surface Chemistry for Enhancing a Latex Homogeneous Immunoassay of C-Reactive Protein (2001)

The role of the solution environment for a light-scattering, latex-particle-enhanced, homogeneous immunoassay of C-reactive protein (CRP) has been investigated in order to assess and optimize the immunoagglutination response. Latex particles of 50-170-nm sizes were covalently coupled with an IgG polyclonal antibody and subjected to an extensive optimization regime. This consisted of conditions responsible, in different degrees, for the principal attractive/repulsive forces affecting both colloidal stability and the antibody/antigen interaction: particle size, antibody concentration, ionic strength and species, pH, and amino acid chemistry of the particle surface. Careful control of these parameters was found to be necessary to achieve the desired effects of balancing high colloidal stability in the absence of antigen but promoting a rapid, sensitive, and dose-dependent agglutination with pathological serum samples. In addition, the estimation of fundamental properties governing intermolecular interaction (i.e. the "Hamaker" constant and critical coagulation concentration) was attempted to order to investigate a simple, practical means of defining a colloidal/immunoassay system under "real conditions" as well as "real time". It is concluded that because each antibody system is unique, a similar optimization should be performed in diagnostic immunoassays of this type to maximize their clinical utility.
A fast and highly sensitive blood culture PCR method for clinical detection of Salmonella enterica serovar Typhi (2010)

This novel blood culture PCR method is superior in speed and sensitivity to both conventional blood culture and PCR assays. Its use in clinical diagnosis may allow early detection of the causative organism and facilitate initiation of prompt treatment among patients with typhoid fever.
Filter Optimization for Self-Homodyne Coherent WDM Systems Using Interleaved Polarization Division Multiplexing (2011)

We examine the impact of filtering on self-homodyne coherent WDM systems using the interleaved polarization division-multiplexing scheme. To investigate the performance limit and to provide more insight into previously obtained experimental results, we perform numerical simulations in which different filter shapes and filter bandwidths are used. It is shown that with proper prefiltering of the data and filtering of the pilot tone in the receiver, performance can approach that of an intradyne system. This would make it possible to implement coherent systems with high spectral efficiency without any digital signal processing in the receiver.
Microencapsulation of mammalian cells in a HEMA‐MMA copolymer: Effects on capsule morphology and permeability (1990)

A new process for preparing uniform microcapsules with a hydroxyethyl methacrylate-methyl methacrylate copolymer (HEMA-MMA) has been devised. Capsule diameters were 900-1000 microns in diameter, (+/- 10-20 microns, +/- SD) depending on the precipitation conditions. The process involved the coextrusion of polymer solution (in PEG 200) and the mammalian cell suspension (here erythrocytes) through a needle assembly which is submerged in a layer of hexadecane which is in turn sitting above a stirred isotonic aqueous solution in a volumetric flask. The needle is repeatedly withdrawn from the hexadecane overlayer shearing a droplet from the needle tip which falls into the water, where the solvent is extracted to precipitate the polymer around the cells to yield the capsules. The morphology of the capsule wall was altered by changing the precipitation bath from phosphate buffered saline (PBS) to 0.3 M glycerol. This resulted in greater macroporosity in the wall, presumably because of the faster precipitation due to the higher solvent/precipitant compatibility with 0.3 M glycerol. The permeability to a series of test solutes (glucose, inulin, albumin, and alcohol dehydrogenase, ADH) increased by a factor of approximately 2, presumably because of the increased macroporosity. Addition of 15% water to the polymer solvent enhanced the macroporosity, presumably by bringing the system closer to the cloud point; however, there was no corresponding increase in permeability. There was a significant decrease in permeability between that of albumin (approximately 69,000 D) and ADH (approximately 150,000 D) suggesting that the molecular weight cut-off of these capsules was on the order of 100,000 D as desired. This process is now being evaluated for the encapsulation of pancreatic islets and other cells of potential clinical interest.
Properties of Acid Sites on TiO2–SiO2 and TiO2–Al2O3 Mixed Oxides Measured by Infrared Spectroscopy (1992)

Abstract Both Lewis and Brönsted acid sites were found on the surface of TiO2–SiO2 mixed oxide, thouth no Brönsted acid sites were detected on the surface of pure TiO2 and SiO2. While on the surface of TiO2–Al2O3 mixed oxide, no Brönsted acid sites were generated. The rate of isomerization of 1-butene was found to be enhanced on the Brönsted acid sites formed on the TiO2–SiO2 mixed oxide.
Molecular Mechanisms in Thrombotic Thrombocytopenic Purpura (2004)

Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolysis. Unlike the typical hemolytic uremic syndrome (HUS), which follows infection with shiga toxin-producing microorganisms, most cases of TTP do not have an obvious etiology. Recent studies revealed that a plasma zinc metalloprotease ADAMTS (a disintegrin and metalloprotease with thrombospondin type 1 motif) 13 cleaves von Willebrand factor in a shear-dependent manner. Deficiency of ADAMTS13, due to autoimmune inhibitors of the protease or genetic mutation in the ADAMTS13 gene, results in a propensity to the development of von Willebrand factor-platelet aggregation and intravascular thrombosis characteristic of TTP. The identification of the molecular defect in TTP raises the prospect that this hitherto mysterious disorder will be managed with a more rationally designed strategy in the near future.
Analysis of TCP-Reno and TCP-Vegas over AOMDV routing protocol for mobile ad hoc network (2010)

A mobile ad hoc network eliminates the complexity of infrastructure configuration and allows wireless devices to communicate with each other on the fly. It does not rely on a base station to coordinate the flow of messages in the network. A primary challenge is to provide each device to maintain the information to properly route traffics using a routing protocol and conveying data packets efficiently using a transport protocol. Many routing protocols and transport protocols are currently being developed to handle the wireless environment efficiently. In this paper, we investigate the performance differences of TCP-Reno and TCP-Vegas utilizing an AOMDV routing protocol. Although TCP-Vegas provides a better throughput than TCP-Reno in a static environment, it suffers performance degradation in a mobile environment, where packet loss rate, throughput, normalized routing load and average delay are measured as performance metrics, as well as discussed by describing strengths and weaknesses of TCP-Reno and TCP-Vegas.
IFN- γ Is Effective in Reducing Infections in the Mouse Model of Chronic Granulomatous Disease (CGD) (2001)

Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p<0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p<0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD.
Experimental support for the foldability–function tradeoff hypothesis: Segregation of the folding nucleus and functional regions in fibroblast growth factor‐1 (2012)

The acquisition of function is often associated with destabilizing mutations, giving rise to the stability-function tradeoff hypothesis. To test whether function is also accommodated at the expense of foldability, fibroblast growth factor-1 (FGF-1) was subjected to a comprehensive φ-value analysis at each of the 11 turn regions. FGF-1, a β-trefoil fold, represents an excellent model system with which to evaluate the influence of function on foldability: because of its threefold symmetric structure, analysis of FGF-1 allows for direct comparisons between symmetry-related regions of the protein that are associated with function to those that are not; thus, a structural basis for regions of foldability can potentially be identified. The resulting φ-value distribution of FGF-1 is highly polarized, with the majority of positions described as either folded-like or denatured-like in the folding transition state. Regions important for folding are shown to be asymmetrically distributed within the protein architecture; furthermore, regions associated with function (i.e., heparin-binding affinity and receptor-binding affinity) are localized to regions of the protein that fold after barrier crossing (late in the folding pathway). These results provide experimental support for the foldability-function tradeoff hypothesis in the evolution of FGF-1. Notably, the results identify the potential for folding redundancy in symmetric protein architecture with important implications for protein evolution and design.