gebhart/patrepeval huggingface dataset:
Functional roles of carboxylate residues comprising the DNA polymerase active site triad of Ty3 reverse transcriptase (2005)

Aspartic acid residues comprising the -D-(aa) n -Y-L-D-D- DNA polymerase active site triad of reverse transcriptase from the Saccharomyces cerevisiae long terminal repeat-retrotransposon Ty3 (Asp151, Asp213 and Asp214) were evaluated via site-directed mutagenesis. An Asp151-->Glu substitution showed a dramatic decrease in catalytic efficiency and a severe translocation defect following initiation of DNA synthesis. In contrast, enzymes harboring the equivalent alteration at Asp213 and Asp214 retained DNA polymerase activity. Asp151-->Asn and Asp213-->Asn substitutions eliminated both polymerase activities. However, while Asp214 of the triad could be replaced by either Asn or Glu, introducing Gln seriously affected processivity. Mutants of the carboxylate triad at positions 151 and 213 also failed to catalyze pyrophosphorolysis. Finally, alterations to the DNA polymerase active site affected RNase H activity, suggesting a close spatial relationship between these N- and C-terminal catalytic centers. Taken together, our data reveal a critical role for Asp151 and Asp213 in catalysis. In contrast, the second carboxylate of the Y-L-D-D motif (Asp214) is not essential for catalysis, and possibly fulfills a structural role. Although Asp214 was most insensitive to substitution with respect to activity of the recombinant enzyme, all alterations at this position were lethal for Ty3 transposition.
Molten‐Salt Corrosion of Silicon Nitride: II, Sodium Sulfate (1988)

The corrosion mechanism of Si 3 N 4 + Na 2 SO 4 /O 2 at 1000°C was investigated. Corrosion of both pure and additive‐containing Si 3 N 4 was studied. The reaction of Si 3 N 4 + Na 2 SO 4 consists of an initial period of slow weight loss due to Na 2 SO 4 vaporization and oxidation‐dissolution. This initial period was the same for all forms of Si 3 N 4 . A second region consisted of further oxidation or near termination of reaction, depending on the additive in the Si 3 N 4 . A 5‐ to 10‐μm yttrium depletion zone was found after corrosion for the Si 3 N 4 with yttria additives. For comparison, Si and SiC were corroded under similar conditions. These materials corroded substantially faster than all forms of Si 3 N 4 .
Telmisartan Improves Insulin Resistance and Modulates Adipose Tissue Macrophage Polarization in High-Fat-Fed Mice (2011)

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.
Page replacement for general caching problems (1999)

Caching (paging) is a well-studied problem in online algorithms, usually studied under the assumption that all pages have a uniform size and a uniform fault cost (uniform caching). However, recent applications related to the web involve situations in which pages can be of dierent sizes and costs. This general caching problem seems more intricate than the uniform version. In particular, the offline case itself is NP-hard. Only a few results exist for the general caching problem [8, 17]. This paper seeks to develop good oine page replacement policies for the general caching problem, with the hope that any insight gained here may lead to good online algorithms. Our first main result is that by using only a small amount of additional memory, say O(1) times the largest page size, we can obtain an O(1)-approximation to the general caching problem. Note that the largest page size is typically a very small fraction of the total cache size, say 1%. Our second result is that when no additional memory is allowed, one can obtain an O(log(M + C))-approximation where M and C denote the cache size and the largest page fault cost, respectively. Our results use a new rounding technique for linear programs which may be of independent interest. We also present a randomized online algorithm for the Bit Model [8] which achieves a competitive ratio of O(ln(1 + 1=c)) while using M(1 + c) memory.
Elevated Postmortem Tryptase in the Absence of Anaphylaxis (1995)

Elevations in tryptase, a recently discovered mast cell enzyme, have been proposed as a postmortem indicator of fatal anaphylaxis. The previous studies had limited numbers of controls and thus the specificity of the test with postmortem samples was not known. Therefore, tryptase was evaluated in postmortem blood samples from 49 autopsy cases where there was no evidence of fatal anaphylaxis. The tryptase was above the normal serum threshold of 1 nanogram/mL (ng/mL) in 31 of these cases. Twenty-four cases had values in the 1 to 5 ng/mL range, two cases were between 5 and 10 ng/mL, and five were greater than 10 ng/mL. One autopsy specimen had a tryptase value of 106 ng/mL. The postmortem interval and the specimen storage condition did not appear to correlate with these elevations in tryptase. Although elevations in the postmortem tryptase remain an important supporting finding in the diagnosis of fatal anaphylaxis, it should not be used alone as the sole criterion for the postmortem diagnosis of anaphylaxis.
Commercial Gestational Surrogacy on The Biopolitcal Horizon (2015)

This article is featured in the journal Tapestries: Interwoven voices of local and global identities, volume 4.
Effects of Vascular Nitric Oxide Bioactivity and Vascular Ageing on Arterial Blood Pressure and Flow Waveforms (2011)

Analysis of blood pressure and flow waveforms may lead to improved diagnosis of arterial dysfunction and disease. This thesis describes experiments to investigate the characteristic alteration of peripheral waveforms produced by stimulated release of vascular nitric oxide (an effect that is attenuated by endothelial dysfunction) and the changes that occur with age. In vivo experiments were conducted in anaesthetised rabbits and in vitro experiments employed a polyurethane model of the human aorta and its principal branches. Blood pressure, blood flow, pulse wave velocities and vessel diameter were recorded in the rabbit abdominal aorta. Equivalent recordings were obtained from the model aorta. Data were analysed in the time domain using wave intensity analysis after separation of reservoir (Windkessel) pressure and wave pressure. Effects of acetylcholine (Ach) and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in vivo. Ach (which promotes endothelial production of nitric oxide) increased wave reflection, whilst L-NAME (which inhibits nitric oxide production) decreased it. These trends were opposite to the expected ones, and do not account for the established effects of nitric oxide on peripheral arterial waveforms. Further work is required to investigate these contradictions. Arterial stiffening in immature and mature rabbits was attempted by supplementing their diet with fructose. Fructose is known to form advanced glycation end-products in arterial walls and hence to stiffen arteries. Unexpectedly, fructose did not affect haemodynamic function. However, immature control rabbits had markedly reduced aortic wave reflection compared to mature control rabbits, indicating that the former have arterial impedances that are better matched for incident wave propagation. Wrapping the model aorta in Clingfilm was used to simulate age- or drug-induced stiffening of the aorta in vivo. Increased pulse pressure was observed, resembling the isolated systolic hypertension prevalent in aged populations. The model has potential for modelling haemodynamic function in health and disease.
Microsolvation Effects on the Excited-State Dynamics of Protonated Tryptophan (2006)

To better understand the complex photophysics of the amino acid tryptophan, which is widely used as a probe of protein structure and dynamics, we have measured electronic spectra of protonated, gas-phase tryptophan solvated with a controlled number of water molecules and cooled to approximately 10 K. We observe that, even at this temperature, the bare molecule exhibits a broad electronic spectrum, implying ultrafast, nonradiative decay of the excited state. Surprisingly, the addition of two water molecules sufficiently lengthens the excited-state lifetime that we obtain a fully vibrationally resolved electronic spectrum. Quantum chemical calculations at the RI-CC2/aug-cc-pVDZ level, together with TDDFT/pw based first-principles MD simulations of the excited-state dynamics, clearly demonstrate how interactions with water destabilize the photodissociative states and increase the excited-state lifetime.
Software framework for runtime application monitoring of fail-safe multi-processor ADAS SoCs (2017)

In advanced driver assistance systems (ADAS), it is very critical to ensure a system malfunction does not cause harm to humans (also referred to as functional safety). Malfunctions could occur due to incorrect software (SW) execution. Many techniques exist to catch systematic SW faults during software and application development. However, without run-time monitoring of key parameters, it is impossible to guarantee a fail-safe system. In this paper, we describe a software framework to monitor application statistics in heterogeneous multiprocessor SoCs targeted for fail-safe ADAS systems. With < 0.5% CPU load overhead per monitor, the proposed framework was found to accurately report statistics for a front camera analytics application.
Staphylococcal Plasmids And Their Replication (1989)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Prevention of Cyclosporine-Induced Nephrotoxicity with Pentoxifylline (1989)

Although cyclosporine (CSA) is established in the prevention of allograft rejection, its use has been associated with dose-limiting toxicities, most notably to the kidney and liver. To date, the pathogenesis of the acute form of nephrotoxicity is unclear but may be related to inhibition of vasodilatory prostaglandins resulting in vasoconstriction and ischemia. The present study investigated the coadministration of CSA with a unique hemorheologic agent, pentoxifylline (PTX), in the murine model. A total of 48 rats were orally dosed with CSA 25 mg/kg for 10 days with either PTX 45 mg/kg i.p. or saline every 12 hr. Posttreatment renal function, assessed by creatinine (CCR) and inulin (CIN) clearances and renal electrolyte handling, was compared with baseline data and between groups. In an attempt to assess prostaglandin-mediated changes in enteral absorption, oral CSA pharmacokinetics with and without PTX were compared to the pharmacokinetics of similar groups (N = 8) administered i.v. CSA. Mean CIN of rats coadministered CSA and PTX (942 +/- 214 microliters/min/g KW) was similar to control rats 884 +/- 185 microliters/min/g KW); both were significantly greater than CSA alone (537 +/- 211 microliters/min/g KW; p less than .01). Likewise, percent of baseline CCR was significantly reduced in rats treated CSA (61 +/- 24%) compared to controls 113 +/- 41%) and rats coadministered PTX (117 +/- 75%; p less than .05). No differences in percent change from baseline electrolyte handling were observed among groups. Further, no differences in CSA pharmacokinetics with or without PTX were found.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid-Functionalized Polyelectrolyte Films as Bioactive Surfaces for Cell Adhesion (2019)

Surfaces were prepared with polyelectrolyte derivatives of poly(styrene- alt-maleic anhydride) (PSMA) functionalized with amino acids of different hydropathy indices, with the aim of evaluating the effect of the chemical functionality of polyelectrolytes on SH-SY5Y neuroblastoma cell adhesion. Functionalizing PSMA derivatives with l-glutamine, l-methionine, and l-tyrosine yielded PSMA-Gln, PSMA-Met, and PSMA-Tyr polyelectrolytes, respectively. We first studied the adsorption behavior of PSMA functionalized with amino acids on silicon wafer surfaces modified with 3-aminopropyltriethoxysilane at pH 4.0 and 7.0 and at low and high ionic strengths. The highest rate of polyelectrolyte adsorption was at pH 4.0 and high ionic strength and was higher with the glutamine and tyrosine films. The advance contact angles (θ<sub>A</sub>) of the polyelectrolyte surfaces showed a moderate effect of ionic strength and pH on polyelectrolyte film wettability, with PSMA-Tyr being slightly more hydrophobic. Atomic force microscopy images of the polyelectrolyte surfaces showed two types of morphology: the well-defined globular nanostructure of PSMA-Met and PSMA-Tyr and densely packed nanofibrous-like structure of PSMA-Gln. The highest level of ionic strength caused a slight decrease in the size of the nanostructure that formed the surface domains, which was reflected in the degree of surface roughness. Cell adhesion assays with the polyelectrolyte film showed that SH-SY5Y neuroblastoma cells cultured on PSMA-Met present a well-extended morphology characterized by a stellate shape, with five or more actin-rich thin processes, whereas SH-SY5Y cells that were seeded on PSMA-Gln and PSMA-Tyr have a round morphology, with fewer and shorter processes. These results indicate that it is possible to modulate the surface characteristics of polyelectrolyte films based on their chemical functionality and environmental parameters such as pH and ionic strength in order to evaluate their effect on cell adhesion. Thus, surfaces prepared from polyelectrolytes functionalized with amino acids are an attractive and simple platform for cell adhesion, which can be used in developing biomaterials with modulated surface properties.
Integrase strand transfer inhibitors in the management of HIV-positive individuals (2014)

The use of highly active antiretroviral therapy against human immunodeficiency virus (HIV) can lead to rare instances of treatment failure and the emergence of drug resistance. HIV drug-resistant strains are archived in cellular reservoirs, and this can exclude the future efficacy of drugs or drug classes against which resistance has emerged. In addition, drug-resistant viruses can be transmitted between individuals. HIV drug resistance has been countered through the constant development of new antiretroviral drugs. Integrase strand transfer inhibitors, that actively block the integration of the HIV genome into the host DNA, represent the most recent antiretroviral drugs. Of these, raltegravir, elvitegravir, and dolutegravir are the only integrase strand transfer inhibitors that have been approved for human therapy by the US Food and Drug Administration. Dolutegravir is unique in its ability to seemingly evade HIV drug resistance in treatment-naïve individuals. Here, we review the use of integrase strand transfer inhibitors in the management of HIV, focusing on HIV resistance.
Abstract 15089: Specificity for Inflammatory Pathways and Myocardial Injury Associated With Coronary Microvascular Dysfunction in Rheumatoid Arthritis (2020)

Background: Coronary microvascular disease (CMD) is associated with increased mortality in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD. However, it is not known whether specific inflammatory pathways implicated in RA play a stronger role than others in the pathogenesis of CMD. The objective of this study was to identify the associations between inflammatory cytokines, CMD, and resultant myocardial injury. Methods: We used baseline data from the first 53 subjects enrolled in a study of RA and CV risk (LiiRA, NCT02714881). LiiRA enrolls RA patients, age&gt;35, prior to TNF inhibitor initiation. All subjects underwent a stress myocardial perfusion PET scan to quantify coronary flow reserve (CFR). CFR is the ratio of myocardial blood flow during maximal hyperemia over that at rest. A lower CFR in the absence of obstructive coronary artery disease (CAD) is indicative of CMD. We tested the association between markers of inflammation and myocardial injury with CFR using the Spearman correlation. Results: Clinical characteristics of LiiRA subjects are shown in Table 1. Baseline cardiac risk factors were uncommon. IL-6, sTNFR2, NT-proBNP were correlated with lower CFR. However, no significant associations were observed between IL-1β, hsCRP, or hs-cTnT (Table 2). Conclusions: Among RA patients with no history of overt CAD, the severity of CMD was correlated with IL-6 and sTNFR2 but not IL-1β or hsCRP. CMD was further associated with increased levels of NT-proBNP but not hs-cTnT. These findings provide potential insight into the mechanisms by which inflammation mediates CMD and resultant myocardial dysfunction.
DRAINAGE OF HIGHWAY AND AIRFIELD PAVEMENTS (ORIGINAL EDITION 1974; REPRINT 1987 WITH UPDATING) (1987)

This book shows engineers how to design and construct pavement drainage systems that will prolong pavement life and minimize maintenance costs. It presents techniques for estimating inflows and designing systems for controlling them to prevent internal flooding and serious damages from: D-cracking, undermining, and other deteriorative effects of excess water. The book also examines the high cost (long term) of building undrained pavements and gives step-by-step procedures for designing good systems. The reprint edition updates the costs of building pavements and the enormous costs of the premature failure of poorly drained ones. Included are noteworthy airfield and highway pavements built in the U.S., Canada, and France using good drainage ideas.
Detection of Building and Infrastructure Instabilities by Automatic Spatiotemporal Analysis of Satellite SAR Interferometry Measurements (2018)

Satellite synthetic aperture radar (SAR) interferometry (InSAR) is a powerful technology to monitor slow ground surface movements. However, the extraction and interpretation of information from big sets of InSAR measurements is a complex and demanding task. In this paper, a new method is presented for automatically detecting potential instability risks affecting buildings and infrastructures, by searching for anomalies in the persistent scatterer (PS) deformations, either in the spatial or in the temporal dimensions. In the spatial dimension, in order to reduce the dataset size and improve data reliability, we utilize a hierarchical clustering method to obtain convergence points that are more trustworthy. Then, we detect deformations characterized by large values and spatial inhomogeneity. In the temporal dimension, we use a signal processing method to decompose the input into two main components: regular periodic deformations and piecewise linear deformations. After removing the periodic component, the velocity variation in each identified temporal partition is analyzed to detect anomalous velocity trends and accelerations. The method has been tested on different sites in China, based on InSAR measurements from COSMO-SkyMed data. The results, verified with in-field surveys, confirm the potential of the method for the automatic detection of deformation anomalies that could cause building or infrastructure stability problems.
The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues (2021)

Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.
The Engineering of Endovascular Stent Technology: A Review (2006)

The evolution of minimally invasive endovascular technology has initiated a significant paradigm shift in the treatment of vascular disease. A fundamental understanding of the science and engineering behind the technology of endovascular stents is a key to their appropriate implementation in practice. Furthermore, the rapid influx of new devices into the field requires practitioners to make their decisions on a foundation of the relative strengths and weaknesses of the various products. Although the principles of their use are not complex, the device design can have a profound effect on the device's functionality. Shape, thickness, coating, material selection, and imaging are just a few of the factors to consider in stent design. Subtle differences may have profound results. This review is designed to provide the reader with an overview of fundamental concepts that will aide the assessment of new technology.
Structural and Solution Chemistry, Antiproliferative Effects, and DNA and Protein Binding Properties of a Series of Dinuclear Gold(III) Compounds with Bipyridyl Ligands (2006)

A series of six dinuclear gold(III) oxo complexes with bipyridyl ligands, of general formula [Au2(N,N)2(mu-O)2][PF6]2 (Auoxo1-Auoxo6) [where N,N = 2,2'-bipyridine (1), 4,4'-di-tert-butyl- (2), 6-methyl- (3), 6-neopentyl- (4), 6-(2,6-dimethylphenyl)- (5), 6,6'-dimethyl-2,2'-bipyridine (6)], were investigated as potential cytotoxic and anticancer agents, and their antiproliferative properties were evaluated in vitro toward the reference A2780 human ovarian carcinoma cell line. While five compounds manifested moderate cytotoxic properties (with IC50 approximately 10-30 microM), the sixth one (Auoxo6), turned out to be approximately 5-15 times more active against both cell lines and will merit further pharmacological studies. The interactions of Auoxo1 and Auoxo6 with a few model proteins (serum albumin, cytochrome c, ubiquitin) and with calf thymus DNA were analyzed in detail by various spectroscopic methods. Both tested compounds manifested a high and peculiar reactivity toward the mentioned model proteins; specific differences were detected in their reactivity with DNA. The mechanistic implications of these results are discussed.