gebhart/patrepeval huggingface dataset:
Automation of a Multiplexed Cell-based Assay to Measure Simultaneously Inhibition and Induction of the Cytochrome P450 Isoform 3A4 by Small Molecule Compounds (2006)

The role that CYP3A4 plays in the metabolism of drugs has been well documented. Therefore, it is essential to understand how this P450 isoform is affected by xenobiotics, to avoid possible drug-drug interactions. Compounds have been shown to either inhibit the activity of CYP3A4 or induce its expression. What is less understood is how a drug can induce gene expression, and inhibit activity of the same isoform. Here we demonstrate the automation of a cell-based multiplexed assay which provides this information. Inhibition and induction were measured using a luminogenic, cell-membrane permeable 3A4-specifi c substrate and a luciferin based reporter gene assay, respectively. Normalization to cell number was also performed using a fl uorescent cell viability assay. DPX-2 cells were dosed for 48 hours with variable concentrations of 54 individual compounds. The combined information from the triplex assay provides a comprehensive picture of a drug’s effects on CYP3A4. The Pregnane X Receptor (PXR) is a nuclear receptor which plays a part in the removal of foreign substances from the body. Upon detecting these xenobiotics, PXR responds by upregulating proteins that can help in the elimination process. One of the most important enzymes involved in the response is the cytochrome P450 3A4 enzyme. CYP3A4 is involved in the metabolism of the widest range of substrates, and metabolizes more than 50% of drugs on the market today. PXR upregulates the expression of this enzyme by binding to the response element of the promotor. Many drugs upregulate the expression of the CYP3A4 gene via PXR. In contrast, a large set of drugs have also shown inhibitory effects on the CYP3A4 enzyme. The upregulation of the CYP3A4 gene or inhibition of the enzyme can result in adverse drug-drug interactions. Less understood and more diffi cult to assess is how certain drugs can induce the expression of the CYP3A4 gene and also inhibit the activity of the enzyme. The DPX2 cell line is a useful tool to assess the effects of a xenobiotic on gene induction and enzyme inhibition. DPX2 cells contain human PXR and a luciferaselinked CYP3A4 promoter reporter construct. Upon activation, PXR binds to the native promoter and the luciferase-linked promoter. Increased CYP3A4 enzyme expressed from the native gene, as well as luciferase expressed from the reporter construct is then expressed. Activity of the enzyme may or may not be inhibited, depending on the effects of the drug. We have used a triplex assay with DPX2 cells to assess the full effects of set of drugs on CYP3A4. The assay was automated in 96-well format using two instruments ideally suited to dispense cells, titrate compounds, transfer and remove media, and dispense compounds and reagents to the assay plates. A multi-mode, monochromator-based reader was then used to read the luminescent and fl uorescent signals from the plates. The combined cell line, assay, and instrumentation create the ideal solution to assess CYP3A4 expression and activity. Overview
Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins (1992)

MAP kinase-activated protein kinase-2 (MAPKAP kinase-2) phosphorylates the serine residues in murine heat shock protein 25 (hsp25) and human heat shock protein 27 (hsp27) which are phosphorylated in vivo in response to growth factors and heat shock, namely Ser15 and Ser86 (hsp25) and Ser15, Ser78 and Ser82 (hsp27). Ser86 of hsp25 and the equivalent residue in hsp27 (Ser82) are phosphorylated preferentially in vitro. The small heat shock protein is present in rabbit skeletal muscle and hsp25 kinase activity in skeletal muscle extracts co-purifies with MAPKAP kinase-2 activity throughout the purification of the latter enzyme. These results suggest that MAPKAP kinase-2 is the enzyme responsible for the phosphorylation of these small heat shock proteins in mammalian cells.
Minimizing damage and contamination in RIE processes by extracted-plasma-parameter analysis (1992)

It is reported that important plasma parameters for reactive ion etching (RIE) processes, such as ion energy and ion flux density, can be extracted from a simple RF waveform analysis at the excitation electrode in a conventional cathode-coupled, parallel-plate plasma RIE system. This analysis does not introduce any contamination or disturbances to the process. By using the extracted plasma parameters, surface damage and contamination in Si substrates induced by reactive ion etching in a SiCl/sub 4/ plasma were investigated. Optimum RIE conditions were then confirmed by studying the relationship between these parameters and the etching performance. It is shown using the experimental data that low-energy high-flux etching is the direction for high performance RIE in future ULSI fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Key Roles of Lewis Acid–Base Pairs on ZnxZryOz in Direct Ethanol/Acetone to Isobutene Conversion (2015)

The effects of surface acidity on the cascade ethanol-to-isobutene conversion were studied using ZnxZryOz catalysts. The ethanol-to-isobutene reaction was found to be limited by the secondary reaction of the key intermediate, acetone, namely the acetone-to-isobutene reaction. Although the catalysts with coexisting Brønsted acidity could catalyze the rate-limiting acetone-to-isobutene reaction, the presence of Brønsted acidity is also detrimental. First, secondary isobutene isomerization is favored, producing a mixture of butene isomers. Second, undesired polymerization and coke formation prevail, leading to rapid catalyst deactivation. Most importantly, both steady-state and kinetic reaction studies as well as FTIR analysis of adsorbed acetone-d6 and D2O unambiguously showed that a highly active and selective nature of balanced Lewis acid-base pairs was masked by the coexisting Brønsted acidity in the aldolization and self-deoxygenation of acetone to isobutene. As a result, ZnxZryOz catalysts with only Lewis acid-base pairs were discovered, on which nearly a theoretical selectivity to isobutene (∼ 88.9%) was successfully achieved, which has never been reported before. Moreover, the absence of Brønsted acidity in such ZnxZryOz catalysts also eliminates the side isobutene isomerization and undesired polymerization/coke reactions, resulting in the production of high purity isobutene with significantly improved catalyst stability (<2% activity loss after 200 h time-on-stream). This work not only demonstrates a balanced Lewis acid-base pair for the highly active and selective cascade ethanol-to-isobutene reaction but also sheds light on the rational design of selective and robust acid-base catalyst for C-C coupling via aldolization reaction.
Practical Routing in Delay-Tolerant Networks (2007)

Delay-tolerant networks (DTNs) have the potential to interconnect devices in regions that current networking technology cannot reach. To realize the DTN vision, routes must be found over multiple unreliable, intermittently-connected hops. In this paper we present a practical routing protocol that uses only observed information about the network. We designed a metric that estimates the average waiting time for each potential next hop. This learned topology information is distributed using a link-state routing protocol, where the link-state packets are "flooded" using epidemic routing. The routing is recomputed each time connections are established, allowing messages to take advantage of unpredictable contacts. A message is forwarded if the topology suggests that the connected node is "closer" to the destination than the current node. We demonstrate through simulation that our protocol provides performance similar to that of schemes that have global knowledge of the network topology, yet without requiring that knowledge. Further, it requires significantly less resources than the alternative, epidemic routing, suggesting that our approach scales better with the number of messages in the network. This performance is achieved with minimal protocol overhead for networks of approximately 100 nodes.
Porous Molecular Solids and Liquids (2017)

Until recently, porous molecular solids were isolated curiosities with properties that were eclipsed by porous frameworks, such as metal-organic frameworks. Now molecules have emerged as a functional materials platform that can have high levels of porosity, good chemical stability, and, uniquely, solution processability. The lack of intermolecular bonding in these materials has also led to new, counterintuitive states of matter, such as porous liquids. Our ability to design these materials has improved significantly due to advances in computational prediction methods.
Power transfer in magnetoelectric resonators (2022)

We derive an analytical model for the power transfer in a magnetoelectric film bulk acoustic resonator consisting of a piezoelectric--magnetostrictive bilayer. The model describes the dynamic magnetostrictive influence on the elastodynamics via an effective frequency-dependent stiffness constant. This allows for the calculation of both the magnetic and elastic power absorption in the resonator as well as of its energy efficiency when such a resonator is considered as a magnetic transducer. The model is then applied to example systems consisting of piezoelectric ScAlN and magnetostrictive CoFeB, Ni, or Terfenol-D layers.
Helicopter Ku-band SATCOM On-the-Move (2006)

There has been substantial development in the past several years to enable broadband, beyond line-of-sight, on-the -move communications to a variety of platforms, in particular ground mobile platforms. Primarily this development has been necessary to support current and envisioned future military operations with widely dispersed forces that depend on high-bandwidth applications. However, rotary-wing aircraft have been left out of this development until recently because of the difficulties in transmission and reception through the moving rotor blades and the extremely limited available space for placing antennas above the rotor blades. In this paper we describe the modifications made to a proven satellite communications on-the-move waveform in order to enable operation of a network of helicopters at Ku-band and present over-the-air emulation results of the performance of that waveform
Zinc electrodeposition and dendritic growth from zinc-halide electrolytes. Final report (1982)

Roughness evolution and dendritic growth restrict the thickness of electroplated zinc during the charge of zinc/halogen batteries and thereby impose operating and economic limitations on their application. Although technologically important, there has so far been little fundamental understanding of dendritic growth and, in the absence of an adequate theory, the phenomenon has been treated mostly empirically. A systematic theoretical and experimental study quantitatively characterizing roughness and dendrite evolution on zinc electrodes is reported here. Comprehensive models were theoretically derived accounting for the initiation and for the propagation rates of dendrites in terms of system parameters including the current, applied potential, reaction kinetics, surface energy, macroscopic and microscopic geometry and convective flow. Morphological stability criteria were applied to define conditions under which electrodes are expected to remain smooth. The macroscopic current and potential distribution in flow cells were calculated and then coupled with analytical models for dendritic growth to provide the growth history and distribution of roughness elements along extended electrodes. Experimental studies of roughness evolution in electrodeposition under well-defined conditions were performed together with kinetic and transport measurements. Careful experimental measurementsand a theoretical study of the impedance of electrodes undergoing electrodeposition were conducted also. Good agreement was observed between themore » experimental dendritic growth measurements and theoretical predictions.« less
Enzymatic Conversion of Prostaglandin H2 to Prostaglandin F2α by Aldehyde Reductase from Human Liver: Comparison to the Prostaglandin F Synthetase from Bovine Lung (1989)

The primary structure of prostaglandin (PG) F synthetase from bovine lung shows 62% similarity with that of human liver aldehyde reductase (EC 1.1.1.2) (Watanabe, K., Fujii, Y., Nakayama, K., Ohkubo, H., Kuramitsu, S., Kagamiyama, H., Nakanishi, S., and Hayaishi, O. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 11-15). We therefore purified human liver aldehyde reductase to homogeneity and compared the immunological and catalytic properties of aldehyde reductase and PGF synthetase. Although both enzymes belong to a group of aldoketoreductases and their molecular weights are essentially identical, aldehyde reductase had no cross-reactivity to anti-PGF synthetase antiserum. Furthermore, there was a difference in the substrate specificity for reduction of PGs between the two enzymes. Aldehyde reductase catalyzed the reduction of PGJ2, delta 12-PGJ2, PGH2, or PGA2, but not that of PGB2, PGD2, or PGE2, whereas PGF synthetase reduced PGD2. The optimum pH, Km value for PGH2, and the turnover number were 6.5, 100 microM, and 3.1 min-1, respectively. The PGH2 9,11-endoperoxide reductase activity of aldehyde reductase was not affected in the presence of a substrate such as p-nitrobenzaldehyde, DL-glyceraldehyde, or 9,10-phenanthrenequinone, suggesting that PGH2 9,11-endoperoxide and other substrates are reduced at different active site(s). The reaction product formed from PGH2 by this enzyme was identified as PGF2 alpha by gas chromatography/mass spectrometry. These results suggest that aldehyde reductase is not exactly identical to PGF synthetase in terms of its immunological property and substrate specificity for PGs, but that this enzyme is also involved in the direct conversion of PGH2 to PGF2 alpha similar to PGF synthetase.
Frontline: Interferon regulatory factor‐1 as a protective gene in intestinal inflammation: role of TCR γ δ T cells and interleukin‐18‐binding protein (2004)

The transcription factor IFN regulatory factor-1 (IRF-1) regulates production and activity of many inflammatory mediators and cells. Here, we investigated the role of IRF-1 in intestinal inflammation using clinical and histologic scores; inflammatory mediators were also measured in colonic tissue. Dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) was administered to wild-type (WT) or IRF-1 knockout (KO) mice. DSS or TNBS led to a dramatic increase in lethality and colitis severity in IRF-1 KO compared with WT mice. Reduced levels of IFN-gamma and IL-18-binding protein (IL-18BP) were observed in the colon of IRF-1 KO mice, whereas levels of inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated STAT-3, chemokines, TNF-alpha, IL-1beta, IL-15, and IL-18 were not significantly changed. Intestinal inflammation was not altered in IFN-gamma KO mice or in WT mice given neutralizing anti-IFN-gamma antibodies, but was increased in mice lacking TCR gamma delta lymphocytes, a population significantly decreased in the intestine of IRF-1-deficient mice. Administration of IL-18BP reversed the increased susceptibility of IRF-1 KO mice to DSS. These results suggest a protective role for IRF-1 in intestinal inflammation, with a possible anti-inflammatory and/or restorative role. IL-18BP and TCR gamma delta cells appear to be critical factors in the anti-inflammatory effects of IRF-1.
Algorithm and hardware design of discrete-time spiking neural networks based on back propagation with binary activations (2017)

We present a new back propagation based training algorithm for discrete-time spiking neural networks (SNN). Inspired by recent deep learning algorithms on binarized neural networks, binary activation with a straight-through gradient estimator is used to model the leaky integrate-fire spiking neuron, overcoming the difficulty in training SNNs using back propagation. Two SNN training algorithms are proposed: (1) SNN with discontinuous integration, which is suitable for rate-coded input spikes, and (2) SNN with continuous integration, which is more general and can handle input spikes with temporal information. Neuromorphic hardware designed in 28nm CMOS exploits the spike sparsity and demonstrates high classification accuracy (>98% on MNIST) and low energy (51.4-773 nJ/image).
Velocity Dependent Adaptations In Motor Unit Firing Rates During Bicep Curls (2021)

Alterations in muscle control during changing contraction velocity are typically inferred from gross amplitude and timing analysis of the surface electromyographic (sEMG) signal [1]. However, more precise alterations can be directly measured from the firings of individual motor units (MUs) - basic units of neuromuscular control that comprise the sEMG signal. PURPOSE: Investigate velocity dependent adaptations in MU firing behavior in the Biceps Brachii during bicep curls using a non-invasive MU action potential recognition technology [2]. Adaptations were investigated separately for the concentric and eccentric phases of the exercise as they are known to present distinct muscle activation patterns [3]. METHODS: 5 healthy participants (3 males, 2 females, 23-32 y.o.) performed bicep curls from full extension to 90̊ flexion with their dominant arm at velocities of 30 and 180 deg/sec while holding a 5 lbs dumbbell. We collected elbow joint angle (Biometrics Ltd.) and sEMG signals from the Biceps Brachii (Galileo sensor, Delsys Inc.). EMG data were sampled at 2000 Hz, filtered between 20-450 Hz, and decomposed into the constituent MU firings. Time-varying MU firing rates were obtained by convolving firing times with a 0.3 sec Hanning window. RESULTS: We observed higher average firing rates in the concentric phase (12.9 ± 2.4 and 16.2 ± 3.5 in pulses per second, or pps, for the slower and faster velocity, respectively) compared to the eccentric phase (12.0 ± 2.3 and 11.9 ± 2.1 pps), in agreement with previously published data [4]. Moreover, with increasing velocity MU firing rates increased consistently during the concentric phase but not during the eccentric phase of the curl. CONCLUSION: Phase specific differences in MU firing rates during bicep curls are magnified when contraction velocity is increased. These data provide novel insights on the neural mechanisms of muscle contraction at varying velocity that have the potential to inform training and rehabilitation. 1) Roberts & Gabaldón. Integr Comp Biol, 2008. 2) De Luca et al. J Neurophysiol, 2015. 3) Hody et al. Front Physiol, 2019. 4) Del Valle, Thomas C. Muscle Nerve, 2005. Support: Funding was provided in part by NINDS (R44HD094626, R44NS077526) and De Luca Foundation (MA).
Septal secretion of protein A in Staphylococcus aureus requires SecA and lipoteichoic acid synthesis (2018)

Surface proteins of <i>Staphylococcus aureus</i> are secreted across septal membranes for assembly into the bacterial cross-wall. This localized secretion requires the YSIRK/GXXS motif signal peptide, however the mechanisms supporting precursor trafficking are not known. We show here that the signal peptide of staphylococcal protein A (SpA) is cleaved at the YSIRK/GXXS motif. A SpA signal peptide mutant defective for YSIRK/GXXS cleavage is also impaired for septal secretion and co-purifies with SecA, SecDF and LtaS. SecA depletion blocks precursor targeting to septal membranes, whereas deletion of <i>secDF</i> diminishes SpA secretion into the cross-wall. Depletion of LtaS blocks lipoteichoic acid synthesis and abolishes SpA precursor trafficking to septal membranes. We propose a model whereby SecA directs SpA precursors to lipoteichoic acid-rich septal membranes for YSIRK/GXXS motif cleavage and secretion into the cross-wall.
DIABETES EPIDEMIOLOGY RESEARCH INTERNATIONAL (2016)

The epidemiology of insulin dependent diabetes mellitus was evaluated to determine the degree to which the disease results from environmental agents and therefore might be prevented. The results of research indicate that insulin dependent diabetes can be produced in animal models by environmental factors, there are major geographical variations in diabetes, certain populations have shown rapid changes in incidence over time, migrants appear to take on the risk of diabetes in their new country, and certain viruses and chemicals cause insulin dependent diabetes in humans. The results of genetic and epidemiological studies also show that at least 60% of insulin dependent diabetes world wide, and perhaps over 95%, is environmentally determined and thus potentially avoidable. It is concluded that the primary worldwide determinants of diabetes are environmental not immunogenetic and that identifying and altering the diabetogenic environmental factor(s) are likely to be more effective and less risky in preventing insulin dependent diabetes than current immunogenetic approaches.
Synthesis and properties of poly[arylene ether (N‐arylenebenzimidazole)]s (1993)

Abstract Poly(arylene ether)s containing N‐arylenebenzimidazole groups were prepared by the aromatic nucleophilic displacement reaction of two new bis(hydroxyphenyl‐N‐arylenebenzimidazole)s with activated aromatic difluorides in sulfolane at 200°C in the presence of anhydrous potassium carbonate. The bis(hydroxyphenyl‐N‐arylenebenzimidazole)s were prepared from bis( o ‐aminoanilino) arylenes and phenyl‐4‐hydroxybenzoate. The polymers were soluble in N‐methyl‐2‐pyrrolidinone and m ‐cresol and exhibited inherent viscosities from 0.37–0.86 dL/g and glass transition temperatures from 219–289°C. Thermogravimetric analyses showed 5% weight losses from 463–506°C in air and 467–522°C in nitrogen. Unoriented thin films exhibited tensile strengths, moduli, and break elongations at 23°C of 10.2–12.5 ksi, 318–365 ksi, and 4–7%, respectively, and at 177°C of 5.1–6.9 ksi, 256–296 ksi, and 1–5%, respectively. A 50 : 50 random copolymer prepared from 1,3‐bis(4‐fluorobenzoyl) benzene, 1,1'‐(4,4'‐biphenylene)‐bis[2‐(4‐hydroxyphenyl)benzimidazole], and 5,5'‐bis[2‐(4‐hydroxyphenyl)benzimidazole] exhibited higher moisture absorption and lower tensile properties than those predicted by a rule of mixtures relationship. The chemical, physical, and mechanical properties of these polymers are discussed. © 1993 John Wiley &amp; Sons, Inc.‡
Delaying Onset of Dementia: Are Two Languages Enough? (2014)

There is an emerging literature suggesting that speaking two or more languages may significantly delay the onset of dementia. Although the mechanisms are unknown, it has been suggested that these may involve cognitive reserve, a concept that has been associated with factors such as higher levels of education, occupational status, social networks, and physical exercise. In the case of bilingualism, cognitive reserve may involve reorganization and strengthening of neural networks that enhance executive control. We review evidence for protective effects of bilingualism from a multicultural perspective involving studies in Toronto and Montreal, Canada, and Hyderabad, India. Reports from Toronto and Hyderabad showed a significant effect of speaking two or more languages in delaying onset of Alzheimer's disease by up to 5 years, whereas the Montreal study showed a significant protective effect of speaking at least four languages and a protective effect of speaking at least two languages in immigrants. Although there were differences in results across studies, a common theme was the significant effect of language use history as one of the factors in determining the onset of Alzheimer's disease. Moreover, the Hyderabad study extended the findings to frontotemporal dementia and vascular dementia.