gebhart/patrepeval huggingface dataset:
Deciphering a Complex Genetic Regulatory Network: The Bacillus Subtilis σW Protein and Intrinsic Resistance to Antimicrobial Compounds (2006)

Bacillus subtilis, a spore-forming soil bacterium, is the preeminent model system for the analysis of gene regulation in Gram-positive bacteria. Early genetic analyses established that this organism uses alternative sigma (sigma) subunits to reprogram RNA polymerase to activate genes required for growth phase transitions, motility, general stress response, and sporulation. Unexpectedly, the genome sequence predicts the presence of an additional seven a subunits: all members of the extracytoplasmic function (ECF) a subfamily of regulators that typically respond to cell envelope stresses. Here, we review our current understanding of one of these a factors, sigmaW, with an emphasis on experimental strategies and approaches. Exposure to cell envelope active antibiotics and toxic peptides triggers a signaling cascade that releases sigmaW from its cognate anti-sigma thereby allowing transcription of approximately 60 sigmaW-dependent genes. These genes encode proteins that inactivate, sequester, or eliminate toxic compounds from the cell.
Myocardial carnitine palmitoyltransferase I as a target for oxidative modification in inflammation and sepsis (2003)

CPT I (outer membrane carnitine palmitoyltransferase I) is a crucial enzyme in myocardial substrate selection. Two isoforms exist in the heart, the liver (L-) and muscle (M-) isoforms, which have different kinetic characteristics and alter in relative amounts during the neonatal/weaning/adult transition. CPT I is a point for control and regulation of fatty acid oxidation via modulation of its activity by malonyl-CoA, the concentration of which is set by acetyl-CoA carboxylase, AMP-activated protein kinase and malonyl-CoA decarboxylase in response to, for example, alterations in glucose supply. Systemic inflammatory responses and sepsis lead to myocardial dysfunction as part of multiple system organ failure. We have shown that: (i) myocardial CPT I activity is inhibited during neonatal sepsis; (ii) on the basis of inhibitor studies this inhibition appears to be of M-CPT I rather than L-CPT I; (iii) nitration of M-CPT I occurs, probably by peroxynitrite, and this may be responsible for the decrease in CPT I activity; (iv) myocardial CPT I activity is also inhibited in another model of systemic inflammatory response, namely intestinal ischaemia/reperfusion injury, but this can prevented by whole-body moderate hypothermia. Inhibition of M-CPT I would be predicted to alter myocardial substrate selection but there are several questions that remain to be answered.
Regulation of NK cells through the 80-kDa TNFR (CD120b) (1995)

By using monoclonal antibody specific for tumor necrosis factor receptor80 (TNFR80) (CD120b) and TNFR60 (CD120a), we determined which receptor transduces the signals involved in activating natural killer (NK) cells. Purified CD56+CD3- large lymphocytes express TNFR80 but not TNFR60 and interleukin-2 (IL-2) up-regulates TNFR80 expression, consistent with NK cells being activated in vivo. Treatment of NK cells with anti-TNFR80 for 18 h enhanced the NK activity detected on K562 target cells mimicking the effect of TNF. In combination with IL-2, TNF enhanced the development of lymphokine-activated killing. However, only anti-TNFR80 abrogated IL-2 induction of lymphokine-activated killer cell activity. The activity of TNF or anti-TNFR80 was selective for NK cytotoxic function because they did not directly mimic IL-2 activation or induce significant proliferation, expression of cell surface activation antigens (CD25 or HLA-DR), or interferon-gamma secretion. These results indicate that TNFR80 is an important signal transducing receptor for the differentiation of NK cells induced by TNF and IL-2.
Investigation of Stormwater Quality Improvements Utilizing Permeable Friction Course (PFC) (2010)

This report describes research into the water quality and hydraulics of the Permeable Friction Course (PFC). Water quality monitoring of 3 locations in the Austin area indicates up to a 90 percent reduction in pollutant discharges from PFC compared to conventional pavement. This reduction is the result of accumulation of pollutants within the pavement and the reduction in pollutants washed off of vehicles during storm events. The project also developed a methodology for measuring permeability of the pavement in situ. The required overcoming several instances where conventional assumptions in permeability measurements were violated. In particular, flow through the pavement at the heads evaluated was nonlinear and not consistent with Darcy’s law. One dimensional steady state and two dimensional dynamic models of flow in PFC were developed. The latter model is capable of predicting surface and subsurface flow from highways of various geometries.
Thermoplastic Processing of Proteins for Film Formation—A Review (2008)

Increasing interest in high-quality food products with increased shelf life and reduced environmental impact has encouraged the study and development of edible and/or biodegradable polymer films and coatings. Edible films provide the opportunity to effectively control mass transfer among different components in a food or between the food and its surrounding environment. The diversity of proteins that results from an almost limitless number of side-chain amino-acid sequential arrangements allows for a wide range of interactions and chemical reactions to take place as proteins denature and cross-link during heat processing. Proteins such as wheat gluten, corn zein, soy protein, myofibrillar proteins, and whey proteins have been successfully formed into films using thermoplastic processes such as compression molding and extrusion. Thermoplastic processing can result in a highly efficient manufacturing method with commercial potential for large-scale production of edible films due to the low moisture levels, high temperatures, and short times used. Addition of water, glycerol, sorbitol, sucrose, and other plasticizers allows the proteins to undergo the glass transition and facilitates deformation and processability without thermal degradation. Target film variables, important in predicting biopackage performance under various conditions, include mechanical, thermal, barrier, and microstructural properties. Comparisons of film properties should be made with care since results depend on parameters such as film-forming materials, film formulation, fabrication method, operating conditions, testing equipment, and testing conditions. Film applications include their use as wraps, pouches, bags, casings, and sachets to protect foods, reduce waste, and improve package recyclability.
A novel polyclonal antibody (CL-B1/29) for immunolocalization of transforming growth factor-beta 2 (TGF-beta 2) in adult mouse. (1990)

A polyclonal antibody (CL-B1/29) raised against a synthetic peptide with an amino acid sequence identical to the first 29 N-terminal residues of bovine bone-derived transforming growth factor-beta 2 (TGF-beta 2) was characterized and used for immunolocalization of TGF-beta 2 in adult mice. Reduced staining of immunoblots and tissue after absorption of the antiserum with the immunizing peptide or with TGF-beta 2 but not with purified TGF-beta 1 demonstrated that the reagent is specific for TGF-beta 2, with little or no crossreactivity with TGF-beta 1. The immunolocalization of TGF-beta 2 was investigated in formalin-fixed, paraffin-embedded cultured cells and murine tissue. Specimens pre-digested with testicular hyaluronidase demonstrated immunostaining predominantly of extracellular connective tissue matrix, whereas specimens pre-digested with pronase E demonstrated primarily cytoplasmic staining. Immunoreactivity was widely distributed in connective tissue, muscle, adsorptive and secretory epithelia, especially of endocrine tissue, and neural tissue of adult mice.
Monte Carlo Simulation of Homo-Epitaxial Growth on Ge(111). (1993)

Ge(111)表面上のホモエピタキシャル成長では,室温でも高速反射電子回折強度(RHEED)が振動を示し,層状成長が起こっているように見えるなど,興味のある振舞いを示す。Ge(111)表面のホモピタキシャル成長を解析するため, solid-on-solid型のモデルを拡張し,結晶成長シミュレーションを行った。成長中の表面モフォロジーについてステップ密度を算出し,これの膜厚に対する変化と,高速反射電子回折強度の振動の実験を比較し,この両者の間に良い対応関係があることを示した。また,この解析法を利用することで,表面の局所的な原子配列に敏感な到着原子の取り込みプロセスが,特に低温成長において重要な役割をしていることを見出した。
Functional reconstitution of the HIV receptors CCR5 and CD4 in liposomes (2002)

Reconstitution of membrane proteins allows their study in a membrane environment that can be manipulated at will. Because membrane proteins have diverse biophysical properties, reconstitution methods have so far been developed for individual proteins on an ad hoc basis. We developed a postinsertion reconstitution method for CCR5, a G protein coupled receptor, with seven transmembrane alpha helices and small ecto- and endodomains. A His6-tagged version of CCR5 was expressed in mammalian cells, purified using the detergent N-dodecyl-beta-d-maltoside (DDM) and reconstituted into preformed liposomal membranes saturated with DDM, removing the detergent with hydrophobic polystyrene beads. We then attempted to incorporate CD4, a protein with a single transmembrane helix and a large hydrophilic ectodomain into liposomal membranes, together with CCR5. Surprisingly, reconstitution of this protein was also achieved by the method. Both proteins were found to be present together in individual liposomes. The reconstituted CCR5 was recognized by several monoclonal antibodies, recognized its natural ligand, and CD4 bound a soluble form of gp120, a subunit of the HIV fusion protein that uses CD4 as a receptor. Moreover, cells expressing the entire fusion protein of HIV bound to the liposomes, indicating that the proteins were intact and that most of them were oriented right side out. Thus, functional coreconstitution of two widely different proteins can be achieved by this method, suggesting that it might be useful for other proteins.
Daclatasvir (Daklinza): The First‐in‐Class HCV NS5A Replication Complex Inhibitor (2015)

Hepatitis C virus (HCV) is estimated to have chronically infected over 175 million people worldwide, causes serious damage to the histology and function of the liver over the course of 20-30 years, gradually progressing to organ failure in a subset of the cases. After an extensive medicinal chemistry optimization campaign that involved evolving chemotypes with molecular properties at the boundaries of the chemical space traditionally considered to be drug-like, Bristol-Myers Squibb (BMS) scientists discovered the highly potent and first-in-class NS5A replication complex inhibitor daclatasvir (DCV, 1). Two additional NS5A inhibitors, ledipasvir (4) and ombitasvir (5), have also been approved for marketing in combination with other direct-acting antiviral agents (DAAs). This chapter discusses key aspects of the discovery and development campaigns that produced DCV along with select highlights from mode of action studies.
Development of Nanopowder Synthesis Using Induction Plasma (2010)

The application of induction plasma technology developed for the synthesis of nanometric powders is summarized. A brief description of the scientific basis for the induction plasma processes is given, followed by the presentation of an induction plasma system developed by Tekna, together with various examples of the nanopowders synthesized using its facilities. The advantages of the induction plasma process over alternative techniques and its adaptability into industrial-scale operation is particularly illustrated. Some specific issues related to the nanopowder synthesis process are also discussed.
Characterization of TR-107, a Novel Chemical Activator of the Human Mitochondrial Protease ClpP (2022)

Abstract We recently described the identification of a new class of small molecule activators of the mitochondrial protease ClpP. These compounds synthesized by Madera Therapeutics showed increased potency of cancer growth inhibition over the related compound ONC201. In this study, we describe chemical optimization and characterization of the next generation of highly potent and selective small molecule ClpP activators (TR compounds) and demonstrate their efficacy against breast cancer models in vitro and in vivo . One of these compounds (TR-107) with excellent potency, specificity and drug-like properties was selected for further evaluation. Examination of TR-107 effects in triple-negative breast cancer (TNBC) cell models showed growth inhibition in the low nanomolar range, equipotent to paclitaxel, in a ClpP-dependent manner. TR-107 reduced specific mitochondrial proteins including OXPHOS and TCA cycle components, in a time, dose and ClpP-dependent manner. Seahorse XF analysis and glucose deprivation experiments confirmed inactivation of OXPHOS and demonstrated an increased dependence on glycolysis following TR-107 exposure. The pharmacokinetic properties of TR-107 were compared to other known ClpP activators including ONC201 and ONC212. TR-107 displayed excellent exposure and serum t 1/2 after oral administration. The antitumor response to TR-107 was investigated using human TNBC MDA-MB-231 cell line-induced xenograft tumors. Oral administration of TR-107 resulted in reduction in tumor volume and extension of survival in the treated compared with vehicle control mice. In summary, we describe the identification of highly potent new ClpP agonists with improved efficacy against TNBC, through targeted inactivation of OXPHOS and disruption of mitochondrial metabolism.
A method for assessing patterns of familial resemblance in complex human pedigrees, with an application to the nevus-count data in Utah kindreds. (1992)

An analytic method is described for estimating phenotypic correlations between pairs of members of specific relationships in pedigrees. In estimating correlations, this new method allows simultaneous adjustment for available covariates such as age, gender, environmental factors, and variables reflecting ascertainment mode, through mean- and variance-regression models. The estimated correlations and regression coefficients corresponding to covariates are consistent and asymptotically normally distributed. Differing from a full-likelihood approach, this new method does not require the assumption of a particular joint distribution of phenotypes from a pedigree, such as the multivariate normal distribution, but instead only requires correct specification of mean- and variance-regression models. Within this framework, missing data, if they are missing completely at random, can be ignored without biasing estimates. The method is illustrated by an application using nevus-count data from 28 Utah kinships. The results from the analysis are that covariate-adjusted nevus counts are correlated between parents and children (correlation .22; P less than .001) and between siblings (correlation .32; P less than .001), while the correlation of -.04 between husband and wife is not significantly different (P = .31) from 0. This result is consistent with a genetic etiology of nevus count.
Management of metastatic tumors of the spine: strategies and operative indications (2001)

The spinal column is the most frequent site of bone metastasis in the body. Spine surgeons are often involved in the care of these patients only after nonoperative management has failed. Because surgery has been viewed as no better than radiotherapy in the treatment of metastasis of the spine, it has only been used as a salvage approach. These views are based on a body of literature in which laminectomy combined with radiotherapy was compared with radiotherapy alone. Anterior approaches to the spine are now popular and familiar to most surgeons. These approaches allow direct access to the metastatic lesion, reconstruction of the anterior vertebral column, and the placement of anterior instrumentation. Outcomes are frequently much better when this combined treatment is used instead of radiotherapy alone. In selected patients, surgery may be desired as first-line therapy before radio- or chemotherapy has been initiated. The controversy surrounding surgery for metastatic spinal disease is reviewed. Treatment strategies, both operative and nonoperative, are presented. Indications and strategies for surgery are also presented, and the supporting literature is reviewed.
Locally Scale-Invariant Convolutional Neural Networks (2014)

Convolutional Neural Networks (ConvNets) have shown excellent results on many visual classification tasks. With the exception of ImageNet, these datasets are carefully crafted such that objects are well-aligned at similar scales. Naturally, the feature learning problem gets more challenging as the amount of variation in the data increases, as the models have to learn to be invariant to certain changes in appearance. Recent results on the ImageNet dataset show that given enough data, ConvNets can learn such invariances producing very discriminative features [1]. But could we do more: use less parameters, less data, learn more discriminative features, if certain invariances were built into the learning process? In this paper we present a simple model that allows ConvNets to learn features in a locally scale-invariant manner without increasing the number of model parameters. We show on a modified MNIST dataset that when faced with scale variation, building in scale-invariance allows ConvNets to learn more discriminative features with reduced chances of over-fitting.
A System for Keyword Search on Textual Streams (2007)

An increasing amount of data is produced in the form of text streams – these can be RSS news feeds, TV closed captions, emails, etc. We study the problem of answering keyword queries on multiple textual streams. We define the result of a keyword query inspired by previous work on keyword search on static databases. A result to a query is a combination of streams “sufficiently correlated” to each other that collectively contain all query keywords within a specified time span. On the algorithmic side, in this paper we focus on the component of continuously monitoring the streams and outputting results as soon as they are available.
Can contemporary racing spikes improve sprint running performance? (2023)

"Can contemporary racing spikes improve sprint running performance?." Footwear Science, 15(sup1), pp. S120–S121Keywords: Locomotionfatiguefootwearperformancebiomechanics Disclosure statementNo potential conflict of interest was reported by the author(s).
Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor (2006)

There is a great need to develop better mechanism-based therapies for prostate cancer. In this investigation, we studied four human prostate cancer cell lines, LNCaP, DU145, LAPC4, and PC3, which differ in response to the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug. Examining the role of intrinsic mitochondrial caspase-dependent apoptosis and caspase-independent, reactive oxygen species (ROS) facilitated cell death, has provided an understanding of mechanisms that may determine the varied response to the histone deacetylase inhibitor. We found striking differences among these cancer cells in constitutive expression and response to suberoylanilide hydroxamic acid in levels of antiapoptotic and proapoptotic proteins, mitochondria membrane integrity, activation of caspases, ROS accumulation, and expression of thioredoxin, the major scavenger of ROS. Identifying these differences can have predictive value in assessing therapeutic response and identifying targets to enhance therapeutic efficacy.
Synthesis of a Hydroxymethylene‐Bridged Galβ(→3)Gal c‐Disaccharide (1992)

Abstract Direct lithiation of the readily available 2‐phenylsulfinyl‐ D ‐galactal 3S furnishes with aldehyde 8 as electrophile in a diastereocontrolled reaction the C ‐disaccharide intermediate 9 . Subsequent removal of the phenylsulfinyl group with Raney nickel and diastereospecific 2b‐hydrogen and 3b‐hydroxy transfer provide the β(1→3)‐connected C ‐disaccharide 11 in high yield. The structure of 11 was deduced from its derivative 12 on the basis of 1 H‐NMR data. Hydrogenolytic O ‐debenzylation gives compound 13 , which is characterized as O ‐acetylated compound 14 .
Enhanced Activity in Parathyroid Hormone-(1–14) and -(1–11): Novel Peptides for Probing Ligand-Receptor Interactions* (2001)

The amino-terminal portion of PTH is critical for PTH-1 receptor (P1Rc) activation. In exploring this component of the ligand receptor interaction, we recently showed that the agonist potency of the weakly active PTH-(1-14)NH(2) peptide can be enhanced by natural amino acid substitutions at several positions, including position 11 (normally leucine). Here we show that the potency of PTH-(1-14)NH(2) can be enhanced by using nonnatural amino acids that increase the length and polarizability of the position 11 side-chain. Thus, in LLC-PK(1) cells stably expressing high levels of the human P1Rc, [homoarginine([Har)(11)]PTH-(1-14)NH(2) was 30-fold more potent for cAMP production than was native PTH-(1-14)NH(2). Combining the homoarginine-11 substitution with other recently identified activity-enhancing substitutions yielded [Ala(3,12),Gln(10),Har(11),Trp(14)]PTH-(1-14)NH(2), which was 1500-fold more potent than PTH-(1-14)NH(2) (EC(50) = 0.12 +/- 0.04 and 190 +/- 20 microM, respectively) and only 63-fold less potent than PTH-(1-34) (EC(50) = 1.9 +/- 0.5 nM). The even shorter analog [Ala(3),Gln(10),Har(11)]PTH-(1-11)NH(2) was also a full cAMP agonist (EC(50) = 3.1 +/- 1.5 microM). Receptor mutations at Phe(184) and Leu(187) located near the boundary of the amino-terminal domain and transmembrane domain-1 severely impaired responsiveness to the PTH-(1-11) analog. Overall, these studies demonstrate that PTH analogs of only 11 amino acids are sufficient for activation of the PTH-1 receptor through interaction with its juxtamembrane region.
Rapid, stable fluid dynamics for computer graphics (1990)

We present a new method for animating water based on a simple, rapid and stable solution of a set of partial differential equations resulting from an approximation to the shallow water equations. The approximation gives rise to a version of the wave equation on a height-field where the wave velocity is proportional to the square root of the depth of the water. The resulting wave equation is then solved with an alternating-direction implicit method on a uniform finite-difference grid. The computational work required for an iteration consists mainly of solving a simple tridiagonal linear system for each row and column of the height field. A single iteration per frame suffices in most cases for convincing animation.Like previous computer-graphics models of wave motion, the new method can generate the effects of wave refraction with depth. Unlike previous models, it also handles wave reflections, net transport of water and boundary conditions with changing topology. As a consequence, the model is suitable for animating phenomena such as flowing rivers, raindrops hitting surfaces and waves in a fish tank as well as the classic phenomenon of waves lapping on a beach. The height-field representation prevents it from easily simulating phenomena such as breaking waves, except perhaps in combination with particle-based fluid models. The water is rendered using a form of caustic shading which simulates the refraction of illuminating rays at the water surface. A wetness map is also used to compute the wetting and drying of sand as the water passes over it.
Binding and Lysing of Blood Clots Using MRX-408 (1998)

The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.