gebhart/patrepeval huggingface dataset:
Discovery of <i>N</i>-Aryl Piperazines as Selective mGluR<sub>5</sub> Potentiators with Improved In Vivo Utility (2010)

This Letter describes the discovery, SAR and in vitro and in vivo pharmacological profile of a novel non-MPEP derived mGlu(5) positive allosteric modulator (PAM) based upon an N-aryl piperazine chemotype. This mGlu(5) chemotype exhibits the ability to act as either a non-competitive antagonist/negative allosteric modulator (NAM) or potentiator of the glutamate response depending on the identity of the amide substituent, i.e., a 'molecular switch'. A rapidly optimized PAM, 10e (VU0364289), was shown to be potent and specific for the rat mGlu(5) receptor and subsequently demonstrated to be efficacious in a clinically relevant rodent model predictive of anti-psychotic activity, thus providing the first example of a centrally active mGluR(5) PAM optimized from an HTS-derived mGluR5 competitive antagonist.
Apolipoprotein E4 Causes Age- and Tau-Dependent Impairment of GABAergic Interneurons, Leading to Learning and Memory Deficits in Mice (2010)

Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease. However, the underlying mechanisms are unclear. We found that female apoE4 knock-in (KI) mice had an age-dependent decrease in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined in the Morris water maze, in aged mice. Treating apoE4-KI mice with daily peritoneal injections of the GABA(A) receptor potentiator pentobarbital at 20 mg/kg for 4 weeks rescued the learning and memory deficits. In neurotoxic apoE4 fragment transgenic mice, hilar GABAergic interneuron loss was even more pronounced and also correlated with the extent of learning and memory deficits. Neurodegeneration and tauopathy occurred earliest in hilar interneurons in apoE4 fragment transgenic mice; eliminating endogenous Tau prevented hilar GABAergic interneuron loss and the learning and memory deficits. The GABA(A) receptor antagonist picrotoxin abolished this rescue, while pentobarbital rescued learning deficits in the presence of endogenous Tau. Thus, apoE4 causes age- and Tau-dependent impairment of hilar GABAergic interneurons, leading to learning and memory deficits in mice. Consequently, reducing Tau and enhancing GABA signaling are potential strategies to treat or prevent apoE4-related Alzheimer's disease.
Water-soluble fullerene (C60) inhibits the osteoclast differentiation and bone destruction in arthritis (2009)

Recently, it has been demonstrated that oxygen free radicals have an important role as a signaling messenger in the receptor activator NFkappaB (RANK) signal pathway required for osteoclast differentiation. The aim of this study was to examine the potential of a strong free-radical scavenger, water-soluble fullerene (C60), as a protective agent against the RANK-induced osteoclastogenesis and osteoclastic bone destruction in arthritis, both in vitro and in vivo. The effects of C60 on the RANK-induced osteoclastogenesis and osteoclastic bone resorption were examined in vitro. Adjuvant-induced arthritic rats were used as an animal model of arthritis. Rats were divided into two subgroups: control and treatment with C60 at 1.0 microM. The left ankle joint was injected intra-articularly with water-soluble C60 (20 microl) in the C60-treated group, while, as a control, the left ankle joint in the control rats received phosphate-buffered saline (20 microl) once weekly for eight weeks. Ankle joint tissues were prepared for histologic analysis. C60 significantly inhibited the responses of osteoclast precursor cells to RANK ligand, including osteoclast differentiation and osteoclastic bone resorption in vitro. In adjuvant-induced arthritic rats, intra-articular treatment with C60 in vivo reduced the number of osteoclasts and alleviated bone resorption and destruction in the joints, while control ankle joints showed progression of joint destruction with time. These findings indicate that C60 downregulates the RANK-induced osteoclast differentiation and is a potential therapeutic agent for inhibition of osteoclastic bone destruction in arthritis.
Nonparametric Blind Super-resolution (2013)

Super resolution (SR) algorithms typically assume that the blur kernel is known (either the Point Spread Function 'PSF' of the camera, or some default low-pass filter, e.g. a Gaussian). However, the performance of SR methods significantly deteriorates when the assumed blur kernel deviates from the true one. We propose a general framework for "blind" super resolution. In particular, we show that: (i) Unlike the common belief, the PSF of the camera is the wrong blur kernel to use in SR algorithms. (ii) We show how the correct SR blur kernel can be recovered directly from the low-resolution image. This is done by exploiting the inherent recurrence property of small natural image patches (either internally within the same image, or externally in a collection of other natural images). In particular, we show that recurrence of small patches across scales of the low-res image (which forms the basis for single-image SR), can also be used for estimating the optimal blur kernel. This leads to significant improvement in SR results.
Ameliorative effect of NAP on laser-induced retinal damage (2011)

Treatment with NAP ameliorates laser-induced retinal lesions. Intravitreal treatment had an early short-term effect while the effect of systemic administration was delayed and prolonged. This treatment may be of clinical significance in reducing laser-induced retinal injuries in humans.
Kinetic and Chemical Evidence for the Inability of Oxidized α<sub>1</sub>-Proteinase Inhibitor to Protect Lung Elastin from Elastolytic Degradation (1984)

The oxidation of human alpha 1-proteinase inhibitor results in the conversion of this protein into a form which cannot protect lung elastin from degradation by elastolytic proteinases. Data indicate that this is primarily because of the lowering of the association rate between the modified inhibitor and neutrophil elastase, as well as in a change in Ki from near 10(-14) to near 10(-10)M. This is consistent with the hypothesis that oxidation of alpha 1-proteinase inhibitor in the lung by cigarette smoke results in a lowering of the protection of this organ from elastolytic degradation.
Full Color Liquid Crystal Light Valve Projector (1985)

A full-color projection display system, incorporating CRT driven liquid crystal light valves, has been designed for use in land-based command and control centers. A novel three-channel, two-projection lens approach has been utilized with this system. A polarizing beamsplitting prism partially pre-polarizes the incoming illumination and directs the light along two parallel paths. Red and green primaries of opposite polarization are directed along one illumination path where they are further separated by a main beamsplitting prism and directed to the red and green channel light valves. The blue primary illumination is directed along the other path where another beamsplitting prism directs the light to the blue channel light valve. The main prisms function as both polarizers and analyzers and direct the output light to the projection lenses. Because the light valves operate in linearly polarized light, it is necessary to remove undue stress birefringence, which, if present, would cause contrast degradation and non-uniformity in the projected image. For that reason, index-matching fluid-filled prisms are used instead of glass. The illumination system includes a 2500-watt air-cooled xenon arc lamp which produces an output of over 1500 lumens in additive white. A novel feature of the projection optics is that while one projection lens handles the red and green primaries the other projection lens (blue channel) can be laterally translated to provide for coarse mechanical registration of the images. Remaining image registration requirements are achieved by both dynamic digital-correction circuitry and by image sensors at the screen that provide feedback to the projector's analog deflection drivers. The projector has a resolution of 1400 TV lines and a contrast ratio of greater than 10:1 in white.
Poly(carbonate-urethane): an isocyanate-free procedure from α,ω-di(cyclic carbonate) telechelic poly(trimethylene carbonate)s (2010)

A simple isocyanate-free method to synthesize poly(trimethylene carbonate hydroxy-urethane)s is described. The strategy first involves the synthesis of α,ω-di(cyclic carbonate) telechelic polycarbonate precursors upon ring-opening polymerization of trimethylene carbonate using a cyclic carbonate alcohol as chain transfer agent, followed by the ring-opening polyaddition of the terminal cyclic carbonate with a diamine. Such poly(carbonate-hydroxyurethane)s exhibit macromolecular carbonate segments of tunable length/molar mass.
Mechanical Harvesting System for Burley Tobacco (1987)

A harvesting-handling system for burley tobacco was modified and field tested to evaluate its performance. The system utilizes a semi-mounted harvester to cut the plants, notch their stalks and convey them to a trailing wagon where workers hang the notched plants on wire-strung portable frames. A grasping chain conveyor was added at the front of the harvest to positively control the plants in the cutting and notching zone. An adjustable frame holder was added to the wagon which allowed the frame to be repositioned to provide working space for completely filling the frame. A quickly adjustable wagon tongue was provided which facilitated turning the machine at end of row. Test results showed that 94.7% of plants were successfully harvested and hung while 2.2% were lost from the conveyors and 3.1% were not properly notched for hanging. Leaves lost amounted to 18.7% and harvest rate was 40.5 plants/min.
Atomic-Scale Imaging in Real and Energy Space Developed in Ultrafast Electron Microscopy (2007)

In this contribution, we report the development of ultrafast electron microscopy (UEM) with atomic-scale real-, energy-, and Fourier-space resolutions. This second-generation UEM provides images, diffraction patterns, and electron energy spectra, and here we demonstrate its potential with applications for nanostructured materials and organometallic crystals. We clearly resolve the separation between atoms in the direct images and the Bragg spots/Debye-Scherrer rings in diffraction and obtain the electronic structure and elemental energies in the electron energy loss spectra (EELS) and energy filtered transmission electron microscopy (EFTEM).
Dysregulation of Tau Phosphorylation in Mouse Brain during Excitotoxic Damage (2009)

Glutamate receptor-mediated excitotoxicity is thought to contribute to the development of Alzheimer's disease (AD), but the underlying mechanism is unknown. In this study, we investigated the dynamic changes of tau phosphorylation and tau-related protein kinases and protein phosphatase 2A (PP2A) in the mouse brain during excitotoxicity induced by intraperitoneal injection of 20 mg/kg kainic acid (KA). We found that KA-induced excitotoxicity led to transient dephosphorylation of tau (within 6 hr post-injection), followed by sustained hyperphosphorylation of tau at multiple sites that are hyperphosphorylated in AD brain. The initial dephosphorylation of tau may result from activation of PP2A, and the sustained hyperphosphorylation may be due mainly to activation of cdk5 and down-regulation of PP2A during the later phase. Because abnormal hyperphosphorylation of tau plays a crucial role in neurodegeneration and in the formation of neurofibrillary tangles, our results suggest that glutamate receptor-mediated excitotoxicity might contribute to AD partially via promoting abnormal hyperphosphorylation of tau in AD brain.
Current Approaches to Group A Streptococcal Vaccine Development (2016)

This chapter describes current efforts to develop safe and effective vaccines to prevent S. pyogenes infections. Although clinical development has been slow, there are a number of available approaches, based on a detailed understanding of the molecular pathogenesis of infection and protective immune responses in animals and humans. The development of M protein-based vaccines has taken full advantage of molecular techniques, rapid and reproducible emm typing methods, and modern molecular engineering that involves gene synthesis and scalable production. Common M epitopes have been engineered into a vaccine that contains a minimal B cell epitope to optimize functional antibody responses. Through genome-based reverse vaccinology, several common antigens have been identified as potential vaccine components. Although the global epidemiology of S. pyogenes infections is still not well defined, a growing amount of information is being used to inform vaccine design. As more vaccines enter clinical trials, there is a need to define common denominators in protocol design, particularly as they relate to safety assessments and efficacy.
Robust Flutter Margins of an F/A-18 Aircraft from Aeroelastic Flight Data (1997)

It is essential to determine eight conditions at which aeroelastic instabilities occur. Flight-test methods can be dangerous and costly, whereas analytical methods may not accurately predict the eutter boundary. An approach to computing eutter boundaries based on the structured singular value is presented. The aeroelastic system is formulated inarobust stabilityframework byparameterizingaround dynamicpressure and introducinguncertainty operators to account for modelingerrors. Flight data can be used tovalidate the robust systemmodel and increase accuracy of the eutter margin estimate. Flutter margins are generated for the F/A-18 Systems Research Aircraft using this method and traditional methods. Extensive e ight data from conditions throughout the eight envelope areanalyzed todeterminethelevelsof uncertaintyinatheoreticalmodel. Therobust marginsdemonstratethat the e ight conditions for e utter may lie closer to the eight envelope than previously estimated by traditional analysis.
Identification and HLA Restriction of Naturally Derived Th1-Cell Epitopes from the Secreted<i>Mycobacterium tuberculosis</i>Antigen 85B Recognized by Antigen-Specific Human CD4<sup>+</sup>T-Cell Lines (2000)

Antigen 85B (Ag85B/MPT59) is a major secreted protein from Mycobacterium tuberculosis which is a promising candidate antigen for inclusion in novel subunit vaccines against tuberculosis (TB). The present study was undertaken to map naturally derived T-cell epitopes from M. tuberculosis Ag85B in relation to major histocompatibility complex (MHC) class II restriction. Antigen-specific CD4(+) T-cell lines were established from HLA-typed TB patients and Mycobacterium bovis BCG vaccinees by stimulation of peripheral blood mononuclear cells with purified Ag85B in vitro. The established T-cell lines were then tested for proliferation and gamma interferon (IFN-gamma) secretion in response to 31 overlapping synthetic peptides (18-mers) covering the entire sequence of the mature protein. The results showed that the epitopes recognized by T-cell lines from TB patients were scattered throughout the Ag85B sequence whereas the epitopes recognized by T-cell lines from BCG vaccinees were located toward the N-terminal part of the antigen. The T-cell epitopes represented by peptides p2 (amino acids [aa] 10 to 27), p3 (aa 19 to 36), and p11 (aa 91 to 108) were frequently recognized by antigen-specific T-cell lines from BCG vaccinees in both proliferation and IFN-gamma assays. MHC restriction analysis demonstrated that individual T-cell lines specifically recognized the complete Ag85B either in association with one of the self HLA-DRB1, DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner. At the epitope level, panel studies showed that peptides p2, p3, and p11 were presented to T cells by HLA-DR-matched as well as mismatched allogeneic antigen-presenting cells, thus representing promiscuous epitopes. The identification of naturally derived peptide epitopes from the M. tuberculosis Ag85B presented to Th1 cells in the context of multiple HLA-DR molecules strongly supports the relevance of this antigen to subunit vaccine design.
Fast Ranking with Additive Ensembles of Oblivious and Non-Oblivious Regression Trees (2016)

Learning-to-Rank models based on additive ensembles of regression trees have been proven to be very effective for scoring query results returned by large-scale Web search engines. Unfortunately, the computational cost of scoring thousands of candidate documents by traversing large ensembles of trees is high. Thus, several works have investigated solutions aimed at improving the efficiency of document scoring by exploiting advanced features of modern CPUs and memory hierarchies. In this article, we present Q uick S corer , a new algorithm that adopts a novel cache-efficient representation of a given tree ensemble, performs an interleaved traversal by means of fast bitwise operations, and supports ensembles of oblivious trees. An extensive and detailed test assessment is conducted on two standard Learning-to-Rank datasets and on a novel very large dataset we made publicly available for conducting significant efficiency tests. The experiments show unprecedented speedups over the best state-of-the-art baselines ranging from 1.9 × to 6.6 × . The analysis of low-level profiling traces shows that Q uick S corer efficiency is due to its cache-aware approach in terms of both data layout and access patterns and to a control flow that entails very low branch mis-prediction rates.
Leaflet Tissue Generation from Microfibrous Heart Valve Leaflet Scaffolds with Native Characteristics (2021)

Mechanical and bioprosthetic valves that are currently applied for replacing diseased heart valves are not fully efficient. Heart valve tissue engineering may solve the issues faced by the prosthetic valves in heart valve replacement. The leaflets of native heart valves have a trilayered structure with layer-specific orientations; thus, it is imperative to develop functional leaflet tissue constructs with a native trilayered, oriented structure. Its key solution is to develop leaflet scaffolds with a native morphology and structure. In this study, microfibrous leaflet scaffolds with a native trilayered and oriented structure were developed in an electrospinning system. The scaffolds were implanted for 3 months in rats subcutaneously to study the scaffold efficiencies in generating functional tissue-engineered leaflet constructs. These in vivo tissue-engineered leaflet constructs had a trilayered, oriented structure similar to native leaflets. The tensile properties of constructs indicated that they were able to endure the hydrodynamic load of the native heart valve. Collagen, glycosaminoglycans, and elastin─the predominant extracellular matrix components of native leaflets─were found sufficiently in the leaflet tissue constructs. The residing cells in the leaflet tissue constructs showed vimentin and α-smooth muscle actin expression, i.e., the constructs were in a growing state. Thus, the trilayered, oriented fibrous leaflet scaffolds produced in this study could be useful to develop heart valve scaffolds for successful heart valve replacements.
Tsunami Arrival Detection with High Frequency (HF) Radar (2012)

Quantitative real-time observations of a tsunami have been limited to deep-water, pressure-sensor observations of changes in the sea surface elevation and observations of sea level fluctuations at the coast, which are essentially point measurements. Constrained by these data, models have been used for predictions and warning of the arrival of a tsunami, but to date no system exists for local detection of an actual incoming wave with a significant warning capability. Networks of coastal high frequency (HF)-radars are now routinely observing surface currents in many countries. We report here on an empirical method for the detection of the initial arrival of a tsunami, and demonstrate its use with results from data measured by fourteen HF radar sites in Japan and USA following the magnitude 9.0 earthquake off Sendai, Japan, on 11 March 2011. The distance offshore at which the tsunami can be detected, and hence the warning time provided, depends on the bathymetry: the wider the shallow continental shelf, the greater this time. We compare arrival times at the radars with those measured by neighboring tide gauges. Arrival times measured by the radars preceded those at neighboring tide gauges by an average of 19 min (Japan) and 15 min (USA) The initial water-height increase due to the tsunami as measured by the tide gauges was moderate, ranging from 0.3 to 2 m. Thus it appears possible to detect even moderate tsunamis using this method. Larger tsunamis could obviously be detected further from the coast. We find that tsunami arrival within the radar coverage area can be announced 8 min (i.e., twice the radar spectral time resolution) after its first appearance. This can provide advance warning of the tsunami approach to the coastline locations.
Memristive switching: physical mechanisms and applications (2014)

Memristive switches are devices which modulate their resistance state depending on the history of the applied current and/or voltage, and have substantial technological potential and as well as scientific interest. In this paper, we review the current state of research on memristive systems. We review the many classes of memristive switching, their physical mechanisms, and their fabrication and operational modes. Next, we discuss the state of the art experimental and modeling/simulation techniques, and the physical insight afforded from these approaches. Finally, we discuss the applications and believed technological potential of these fascinating and exciting devices.
Right precordial leads V4R and V5R in ECG detection of acute ST elevation mi associated with proximal right coronary artery occlusion (2005)

ST elevation myocardial infarction (STEMI) in the right ventricle (RV) associated with right coronary artery (RCA) occlusion is known to have high hospital mortality. The hypothesis tested in this study is: right precordial leads V4R and V5R help detect STEMI in the right ventricle. ECGs from 1,970 subjects were collected in Ruijin Hospital (n=1,342), Shanghai, China and Lund University Hospital, Lund (n=565), Sweden. All ECGs were recorded with additional leads on the right precordial location in V4R and V5R. Our results show that the subjects with middle to upper RCA occlusion often show ST elevation in leads V4R and V5R and ST depression in lateral leads I, aVL, V5-V6, and are often undetected as STEMI or AMI in the standard 12-lead ECG. We conclude that adding V4R and V5R to standard ECG recording in assessing patients presenting with acute coronary syndrome is an easy and convenient way to increases the sensitivity of STEMI detection