gebhart/patrepeval huggingface dataset:
THE EFFECT OF THE CALCIUM ION ANTAGONIST 8‐(N,N‐DIETHYLAMINO)‐OCTYL‐3,4,5‐TRIMETHOXYBENZOATEON MALIGNANT HYPERPYREXIA‐SUSCEPTIBLE PORCINE SKELETAL MUSCLE (1983)

In malignant hyperpyrexia susceptible (MHS) porcine skeletal muscle, a low concentration (100 mumol/l) of the calcium ion antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) inhibited KCl-induced contractures, but potentiated contractures induced by halothane, caffeine and succinylcholine. Higher concentrations of TMB-8 (333 mumol/l to 1 mmol/l) contracted MHS muscle, but had little effect on muscle tension in control preparations. Treatments which inhibit excitation-contraction coupling abolished TMB-8-induced hyper-reactivity in MHS muscle. TMB-8 (50 mumol/l and 1 mmol/l) did not alter 45Ca2+ levels in actively loaded microsomal preparations from MHS swine. These results suggest that in malignant hyperpyrexia the primary abnormality occurs proximal to the release of calcium from the sarcoplasmic reticulum, probably at the level of excitation-contraction coupling.
The interference of copper, iron and aluminum with hydrogen peroxide and its effects on reductive leaching of LiNi1/3Mn1/3Co1/3O2 (2021)

Copper and iron are known to be effective alternative reducing agents to H2O2 in Li-ion battery leaching. The aim of this work is to study the effect of added H2O2 on its overconsumption to the side reactions such as oxidation of copper, iron, and aluminum in leaching of NMC 111 active material. The interactions between the reducing agents separately were first investigated (T = 30 °C, [H2SO4] = 2 M, t = 120 min). Elemental copper was found to be a less efficient reducing agent (78%) compared to aluminum (100%) in terms of Fe3+ reduced to Fe2+. Nevertheless, copper exhibited much higher rate of iron reduction than aluminum. Additionally, aqueous copper ions were found to cement on aluminum surface and redissolve in the presence of iron, thus acting as the metallic reducing agent. In contrast, in the presence of H2O2 ferrous iron and copper were rapidly oxidized resulting in the consumption of all reducing agents. These effects were confirmed also during the leaching of NMC (T = 30 °C, [H2SO4] = 1.5 M, t = 120 min), which demonstrated that the leaching efficiency markedly decreased (∼63%) in the presence of H2O2 and Cu when compared to H2O2 alone (∼78%). Furthermore, results from NMC leaching showed that when copper-iron reductant or H2O2 were added separately, a much higher leaching efficiency was achieved (∼66% and ∼78%, respectively) in contrast to being added together (∼58%).
Self-Assembled Supramolecular Films Derived from Marine Deoxyribonucleic Acid (DNA)−Cationic Surfactant Complexes:  Large-Scale Preparation and Optical and Thermal Properties (2001)

Series of polyelectrolyte−surfactant complexes, DNA−cationic surfactant complexes (cetyltrimethylammonium, cetylpyridinium, and cetylbenzyldimethylammonium), and their self-assembled bulk film materials were prepared on a large scale. Circular dichroism (CD) analysis indicated that the right-handed double helix structure of DNA was retained in these bulk film materials. TGA analysis suggested that 4 molecules of water were required to retain the B-type conformation of the DNA helix in the self-assembled bulk film materials. In addition, it revealed that DNA and the DNA−surfactant complex film materials were thermostable up to as high as 180 °C. Thermodynamical analysis indicated that these film materials were thermo-extensive over a temperature range from 100 to 148 °C. The DNA conformation in the supramolecular complex films can be reversibly tuned by changing the environmental humidity. Film formation was found to occur by self-assembly and self-organization with evaporation of solvent molecules. Various functional dyes such as laser dye, NLO dye, and photochromic dye could easily be incorporated in the self-assembled supramolecular complex films as adducts. Studies of the induced CD spectra demonstrated that 4[4-(dimethylamino)styryl]-1-dococylpyridinium (DMASDPB) could orient on the chiral nanotemplates of DNA in the self-assembled films. UV−vis analysis indicated that these film materials have high transparency from 300 to about 1000 nm. These self-assembled functional-dye-containing DNA−surfactant complex materials, with good processability for multilayer integration into large-area devices, will have promising applications in molecular optical and molecular optoelectronic fields.
IDSA Guidelines for Diagnosis and Treatment of Asymptomatic Bacteriuria (2005)

The Infectious Diseases Society of America (IDSA) has released evidence-based recommendations for the diagnosis and treatment of asymptomatic bacteriuria in adults.
PIAS1-mediated SUMOylation of influenza A virus PB2 restricts viral replication and virulence (2022)

Host defense systems employ posttranslational modifications to protect against invading pathogens. Here, we found that protein inhibitor of activated STAT 1 (PIAS1) interacts with the nucleoprotein (NP), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) of influenza A virus (IAV). Lentiviral-mediated stable overexpression of PIAS1 dramatically suppressed the replication of IAV, whereas siRNA knockdown or CRISPR/Cas9 knockout of PIAS1 expression significantly increased virus growth. The expression of PIAS1 was significantly induced upon IAV infection in both cell culture and mice, and PIAS1 was involved in the overall increase in cellular SUMOylation induced by IAV infection. We found that PIAS1 inhibited the activity of the viral RNP complex, whereas the C351S or W372A mutant of PIAS1, which lacks the SUMO E3 ligase activity, lost the ability to suppress the activity of the viral RNP complex. Notably, the SUMO E3 ligase activity of PIAS1 catalyzed robust SUMOylation of PB2, but had no role in PB1 SUMOylation and a minimal role in NP SUMOylation. Moreover, PIAS1-mediated SUMOylation remarkably reduced the stability of IAV PB2. When tested in vivo, we found that the downregulation of Pias1 expression in mice enhanced the growth and virulence of IAV. Together, our findings define PIAS1 as a restriction factor for the replication and pathogenesis of IAV.
Design, synthesis, and evaluation of an isotopic labeling strategy for studying fatty acid–protein binding by NMR (2008)

Here we describe the synthesis and evaluation of a new isotopic labeling strategy for fatty acids to be used as probes for studying ligand binding by NMR. We synthesized palmitic acid with carbons C-3 through C-16 perdeuterated, C-1 and C-2 with 13C atoms and hydrogens at C-2. Our strategy began with commercially available perdeuterated myristic acid and built up to palmitic acid using a Horner-Wadsworth-Emmons reaction. To evaluate the power of this isotopic enrichment strategy, we evaluated ligand binding to a prototypical member of the intracellular lipid binding protein family, FABP2. This small 15 kDa protein is well known to bind fatty acids with high affinity, and we used this system to illustrate the spectral filtering abilities of our described labeling strategy. Herein we show how having two vicinal 13C-enriched carbons, two hydrogens at the alpha-position, and a perdeuterated aliphatic tail allows the efficient use of multidimensional NMR experiments to effectively filter all background resonances from the protein and facilitate the study of ligand binding.
The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation (2017)

Bisphenol-A (BPA), a widely used synthetic compound in plastics, disrupts endocrine function and interferes with physiological actions of endogenous gonadal hormones. Chronic effects of BPA on reproductive function, learning and memory, brain structure, and social behavior have been intensively investigated. However, less is known about the influence of BPA on long-term potentiation (LTP), one of the major cellular mechanisms that underlie learning and memory. In the present study, for the first time we investigated the effect of different doses of BPA on hippocampal LTP in rat brain slices. We found a biphasic effect of BPA on LTP in the dentate gyrus: exposure to BPA at a low dose (100 nM) enhanced LTP and exposure to BPA at a high dose (1000 nM) inhibited LTP compared with vehicle controls. The rapid facilitatory effect of low-dose BPA on hippocampal LTP required membrane-associated estrogen receptor (ER) and involved activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Coadministration of 17<i>β</i>-estradiol (E<sub>2</sub>, the primary estrogen hormone) and BPA (100 nM) abolished both the BPA-induced enhancement of LTP and the E<sub>2</sub>-induced enhancement of baseline fEPSP, suggesting a complex interaction between BPA- and E<sub>2</sub>-mediated signaling pathways. Our investigation implies that even nanomolar levels of endocrine disrupters (e.g., BPA) can induce significant effects on hippocampal LTP.
Evaluation of the US Army Research Laboratory Squeeze 5 Magnetic Flux Compression Generator (2016)

Abstract : The US Army Research Laboratory has a program to develop a Magnetic Flux Compression device capable of generating a 2 mega-ampere peak output current. This report details the experimental results of the Squeeze 5 device. The objective was to improve the output current and operating efficiency over the previous Squeeze 4 device. Several different loss mechanisms were evaluated, such as magnetic field diffusion, armature cracking, high-voltage insulation, and electrical arcing.
Unexpected Interactions between Sol−Gel Silica Glass and Guest Molecules. Extraction of Aromatic Hydrocarbons into Polar Silica from Hydrophobic Solvents (2000)

Properties of a solute may differ greatly between a free solution and that solution confined in pores of a sol−gel glass. We studied the entry of various aromatic organic compounds from solution into the monolith of sol−gel silica immersed in this solution. Partitioning of the solute is quantified by the uptake coefficient, the ratio of its concentrations in the glass and in the surrounding solution at equilibrium. The dependence of this coefficient on the solvent gives insight into possible interactions between the solute and the silica matrix. We report the uptake of 31 compounds altogether: 18 halogen derivatives of benzene; 5 condensed (fused) aromatics; and stilbene and three substituted derivatives of it, each in both cis and trans configurations. When the solvent is hexane, the uptake coefficients are as follows: 1.0−1.9 for the halobenzenes; 3.0−4.6 for the hydrocarbons; and 3.3−4.9 for the stilbenes. When the solvent is carbon tetrachloride or dichloromethane, the uptake coefficients become 0.82−1.39 for the hydrocarbons and 0.90−1.25 for the stilbenes. The excessive uptake of organic compounds from hexane is unexpected, for it amounts to extraction of nonpolar or slightly polar solutes from a nonpolar solvent into a polar interior of silica glass. The solute−silica interactions responsible for this extraction are not of the van der Waals type. Our findings are consistent with hydrogen bonding between the aromatic π system in the solutes and the hydroxyl groups on the silica surface. Hexane cannot interact with this surface but dichloromethane and carbon tetrachloride can: they shield the hydroxyl groups from the organic solvents and thus suppress the hydrogen bonding. This explanation is supported by the emission spectra of the aromatic compound pyrene when it is dissolved in acetonitrile, dichloromethane, cyclohexyl chloride, and hexane and when it is taken up by monoliths of sol−gel silica from these four solutions. The relative intensities of the emission bands designated III and I change greatly when pyrene is taken up from hexane but remain unchanged when it is taken up from the other three solvents. Evidently, hexane does not, whereas the other three solvents do, line the silica surface and shield it from approach by pyrene molecules. Even though solute molecules are much smaller than the pores in the sol−gel glass, diffusion of these molecules into the monolith may result in an uneven partitioning at equilibrium. This fact must be taken into consideration in the design of biosensors, immobilized catalysts, and other composite materials because their function depends on the entry of analytes, substrates, and other chemicals into the glass matrix.
Ontogeny of ipsilateral corticospinal projections: A developmental study with transcranial magnetic stimulation (1997)

Transcranial magnetic stimulation (TMS) has been used to describe the maturation of the corticospinal tract in children. Ipsilateral corticospinal connections have been demonstrated with TMS in patients with congenital mirror movements, in patients after hemispherectomy, and in children with hemiplegic cerebral palsy. The goal of the study was to find out whether corticospinal ipsilateral projections in children can be demonstrated during the first decade of life as part of normal ontogeny. For this purpose, we examined 50 normal children (age range, 3-11 years) with focal TMS over the left and right hemispheres to target muscles in proximal and distal parts of the upper extremity (first dorsal interosseus, biceps brachii, and brachioradialis). To lower the stimulation threshold, we stimulated under voluntary preinnervation. In two-thirds of the children we elicited ipsilateral motor evoked potentials (MEPs). This occurred more often in proximal than in distal muscles. The latency of the ipsilateral MEPs was about 12 to 14 msec longer than the usual contralateral response. From the age of 10, and in adults, ipsilateral MEPs could not be detected. Also considering lesion data from adult patients, the most likely explanation for the disappearance of ipsilateral corticospinal connections after the age of 10 years is an increasing transcallosal inhibitory influence during development. The presence of ipsilateral corticospinal connections appears to be a normal state in ontogeny.
Ras inhibition via direct Ras binding—is there a path forward? (2012)

Three decades after identification of the Ras oncogene, no effective treatments for Ras mutant tumors are available despite intensive drug discovery efforts. Here we critically review the attempts to inhibit Ras function via direct binding of small molecules at the Ras surface with the aim to disrupt its interaction with other proteins. Multiple binders at different binding sites have been discovered, and recent efforts afforded crystal structures of Ras-binder complexes. Albeit with low affinities, many of the binders were shown to impart inhibitory activities, and inhibition of nucleotide exchange as a consequence of disrupting the Ras-SOS interaction has been the most commonly identified mode of action. We see two key challenges in the development of these early starting points: Enhancing binding affinities and achieving selectivity, both against other GTPases and for mutant Ras over the wildtype form. In light of the large unmet medical need, we encourage the continued search for functionally active Ras binders, and we believe that integrated use of biophysical and biochemical tools will provide the highest chances for success. Given the failures experienced in the past and the significant hurdles ahead, we propose that this challenge be tackled through alliances between industry and academia.
CRYSTALLOGRAPHICALLY ALIGNED TERFENOL-D/POLYMER COMPOSITES FOR A HYBRID SONAR DEVICE (2006)

ABSTRACT Crystallographically-aligned magnetostrictive particle (CAMP) composites offer increased bandwidth and durability when compared to monolithic and laminated magnetostrictive systems. CAMP composites were evaluated under combined magnetic, thermal, and mechanical loading to determine fundamental properties used for the design of sonar transducers that incorporate these materials. Here, we examine the minor loop performance of the CAMP composites, i.e. the linear region of the strain field curve. The measurements demonstrate the benefits of the CAMP Composite technology for sonar applications, achieving strain output near that of monolithic Terfenol-D, while increasing bandwidth and durability. All volume fractions exhibited low minor loop hysteresis, and low temperature dependence.
AT-527 is a potent in vitro replication inhibitor of SARS-CoV-2, the virus responsible for the COVID-19 pandemic (2020)

ABSTRACT AT-527, an orally administered double prodrug of a guanosine nucleotide analog, has been shown previously to be highly efficacious and well tolerated in HCV-infected subjects. Herein we report the potent in vitro activity of AT-511, the free base form of AT-527, against several coronaviruses, including SARS-CoV-2, the causative agent of COVID-19. In normal human airway epithelial (HAE) cell preparations, the average concentration of AT-511 required to inhibit replication of SARS-CoV-2 by 90% (EC 90 ) was 0.5 µM, very similar to the EC 90 for AT-511 against HCoV-229E, HCoV-OC43 and SARS-CoV in Huh-7 cells. No cytotoxicity was observed for AT-511 in any of the antiviral assays up to the highest concentration tested (100 µM). Surprisingly, AT-511 was 30-fold less active against MERS-CoV. This differential activity may provide a clue to the apparent unique mechanism of action of the guanosine triphosphate analog formed from AT-527.
ADAPT: Algorithmic Differentiation Applied to Floating-Point Precision Tuning (2018)

HPC applications use floating point arithmetic operations extensively to solve computational problems. Mixed-precision computing seeks to use the lowest precision data type that is sufficient to achieve a desired accuracy, improving performance and reducing power consumption. Manually optimizing a program to use mixed precision is challenging as it not only requires extensive knowledge about the numerical behavior of the algorithm but also estimates of the rounding errors. In this work, we present ADAPT, a scalable approach for mixed-precision analysis on HPC workloads using algorithmic differentiation to provide accurate estimates about the final output error. ADAPT provides a floating-point precision sensitivity profile while incurring an overhead of only a constant multiple of the original computation irrespective of the number of variables analyzed. The sensitivity profile can be used to make algorithmic choices and to develop mixed-precision configurations of a program. We evaluate ADAPT on six benchmarks and a proxy application (LULESH) and show that we are able to achieve a speedup of 1.2× on the proxy application.
Requirement for Zebrafish Ataxin-7 in Differentiation of Photoreceptors and Cerebellar Neurons (2012)

The expansion of a polyglutamine (polyQ) tract in the N-terminal region of ataxin-7 (atxn7) is the causative event in spinocerebellar ataxia type 7 (SCA7), an autosomal dominant neurodegenerative disorder mainly characterized by progressive, selective loss of rod-cone photoreceptors and cerebellar Purkinje and granule cells. The molecular and cellular processes underlying this restricted neuronal vulnerability, which contrasts with the broad expression pattern of atxn7, remains one of the most enigmatic features of SCA7, and more generally of all polyQ disorders. To gain insight into this specific neuronal vulnerability and achieve a better understanding of atxn7 function, we carried out a functional analysis of this protein in the teleost fish Danio rerio. We characterized the zebrafish atxn7 gene and its transcription pattern, and by making use of morpholino-oligonucleotide-mediated gene inactivation, we analysed the phenotypes induced following mild or severe zebrafish atxn7 depletion. Severe or nearly complete zebrafish atxn7 loss-of-function markedly impaired embryonic development, leading to both early embryonic lethality and severely deformed embryos. More importantly, in relation to SCA7, moderate depletion of the protein specifically, albeit partially, prevented the differentiation of both retina photoreceptors and cerebellar Purkinje and granule cells. In addition, [1-232] human atxn7 fragment rescued these phenotypes showing strong function conservation of this protein through evolution. The specific requirement for zebrafish atxn7 in the proper differentiation of cerebellar neurons provides, to our knowledge, the first in vivo evidence of a direct functional relationship between atxn7 and the differentiation of Purkinje and granule cells, the most crucial neurons affected in SCA7 and most other polyQ-mediated SCAs. These findings further suggest that altered protein function may play a role in the pathophysiology of the disease, an important step toward the development of future therapeutic strategies.
Supplementary Table S1 from Co-occurring Genomic Alterations Define Major Subsets of <i>KRAS</i>-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities (2023)

&lt;p&gt;Supplementary Table S1. Individual KRAS, STK11/LKB1, TP53, ATM and KEAP1 somatic mutations from the indicated clinical cohorts.&lt;/p&gt;
Dorsal Root Ganglion Neurons Innervating Skeletal Muscle Respond to Physiological Combinations of Protons, ATP, and Lactate Mediated by ASIC, P2X, and TRPV1 (2008)

The adequate stimuli and molecular receptors for muscle metaboreceptors and nociceptors are still under investigation. We used calcium imaging of cultured primary sensory dorsal root ganglion (DRG) neurons from C57Bl/6 mice to determine candidates for metabolites that could be the adequate stimuli and receptors that could detect these stimuli. Retrograde DiI labeling determined that some of these neurons innervated skeletal muscle. We found that combinations of protons, ATP, and lactate were much more effective than individually applied compounds for activating rapid calcium increases in muscle-innervating dorsal root ganglion neurons. Antagonists for P2X, ASIC, and TRPV1 receptors suggested that these three receptors act together to detect protons, ATP, and lactate when presented together in physiologically relevant concentrations. Two populations of muscle-innervating DRG neurons were found. One responded to low metabolite levels (likely nonnoxious) and used ASIC3, P2X5, and TRPV1 as molecular receptors to detect these metabolites. The other responded to high levels of metabolites (likely noxious) and used ASIC3, P2X4, and TRPV1 as their molecular receptors. We conclude that a combination of ASIC, P2X5 and/or P2X4, and TRPV1 are the molecular receptors used to detect metabolites by muscle-innervating sensory neurons. We further conclude that the adequate stimuli for muscle metaboreceptors and nociceptors are combinations of protons, ATP, and lactate.
Pilot trial of low‐dose naltrexone and quality of life in multiple sclerosis (2010)

LDN significantly improved mental health quality of life indices. Further studies with LDN in MS are warranted.
Cryogenic Performance of Microfabricated Surface Ion Traps. (2020)

Abstract not provided.