gebhart/patrepeval huggingface dataset:
RNA-Dependent Cysteine Biosynthesis in Bacteria and Archaea (2017)

The diversity of the genetic code systems used by microbes on earth is yet to be elucidated. It is known that certain methanogenic archaea employ an alternative system for cysteine (Cys) biosynthesis and encoding; tRNA<sup>Cys</sup> is first acylated with phosphoserine (Sep) by <i>O</i>-phosphoseryl-tRNA synthetase (SepRS) and then converted to Cys-tRNA<sup>Cys</sup> by Sep-tRNA:Cys-tRNA synthase (SepCysS). In this study, we searched all genomic and metagenomic protein sequence data in the Integrated Microbial Genomes (IMG) system and at the NCBI to reveal new clades of SepRS and SepCysS proteins belonging to diverse archaea in the four major groups (DPANN, <i>Euryarchaeota</i>, TACK, and Asgard) and two groups of bacteria ("<i>Candidatus</i> Parcubacteria" and <i>Chloroflexi</i>). Bacterial SepRS and SepCysS charged bacterial tRNA<sup>Cys</sup> species with cysteine <i>in vitro</i> Homologs of SepCysE, a scaffold protein facilitating SepRS⋅SepCysS complex assembly in Euryarchaeota class I methanogens, are found in a few groups of TACK and Asgard archaea, whereas the C-terminally truncated homologs exist fused or genetically coupled with diverse SepCysS species. Investigation of the selenocysteine (Sec)- and pyrrolysine (Pyl)-utilizing traits in SepRS-utilizing archaea and bacteria revealed that the archaea carrying full-length SepCysE employ Sec and that SepRS is often found in Pyl-utilizing archaea and <i>Chloroflexi</i> bacteria. We discuss possible contributions of the SepRS-SepCysS system for sulfur assimilation, methanogenesis, and other metabolic processes requiring large amounts of iron-sulfur enzymes or Pyl-containing enzymes.<b>IMPORTANCE</b> Comprehensive analyses of all genomic and metagenomic protein sequence data in public databases revealed the distribution and evolution of an alternative cysteine-encoding system in diverse archaea and bacteria. The finding that the SepRS-SepCysS-SepCysE- and the selenocysteine-encoding systems are shared by the <i>Euryarchaeota</i> class I methanogens, the <i>Crenarchaeota</i> AK8/W8A-19 group, and an Asgard archaeon suggests that ancient archaea may have used both systems. In contrast, bacteria may have obtained the SepRS-SepCysS system from archaea. The SepRS-SepCysS system sometimes coexists with a pyrrolysine-encoding system in both archaea and bacteria. Our results provide additional bioinformatic evidence for the contribution of the SepRS-SepCysS system for sulfur assimilation and diverse metabolisms which require vast amounts of iron-sulfur enzymes and proteins. Among these biological activities, methanogenesis, methylamine metabolism, and organohalide respiration may have local and global effects on earth. Taken together, uncultured bacteria and archaea provide an expanded record of the evolution of the genetic code.
THE PREVENTION OF POST‐APPENDICECTOMY SEPSIS BY METRONIDAZOLE AND CEFAZOLIN: A CONTROLLED DOUBLE BLIND TRIAL6 (1980)

A double blind, randomized, controlled trial was carried out at two hospitals to try the effect of metronidazole, which is effective against most anaerobes, and cefazolin, which is effective against many aerobic organisms, singly and in combination, on the incidence of wound sepsis following appendicectomy. Patients were placed at random into one of four groups; to receive metronidazole and placebo, cefazolin and placebo, metronidazole and cefazolin, or double placebo. Patients with generalized peritonitis were excluded for ethical reasons. Treatment was started before operation and continued eight-hourly for twenty-four hours. All patients in the trial were followed up at about two weeks after discharge from hospital and their wounds inspected. Two hundred and seventy-one patients were assessed. Sepsis rates at the two hospitals were similar. On the untreated controls, 30% discharged pus from their wounds, and in the groups receiving one drug only, about 20%. In those receiving both drugs the infection rate was 3%, a highly significant difference from that in the other three groups.
Strategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug Discovery (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStrategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug DiscoveryE. M. Gordon, M. A. Gallop, and D. V. PatelView Author Information Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, California 94304 Cite this: Acc. Chem. Res. 1996, 29, 3, 144–154Publication Date (Web):March 13, 1996Publication History Received26 September 1995Published online13 March 1996Published inissue 13 March 1996https://pubs.acs.org/doi/10.1021/ar950170uhttps://doi.org/10.1021/ar950170uresearch-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1919Altmetric-Citations224LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Organic polymers,Peptides and proteins,Solid phase synthesis,Solids Get e-Alerts
Expression of Various NCAM Isoforms in Human Embryonic Muscles: Correlation with Myosin Heavy Chain Phenotypes (1992)

Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.
Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection (2008)

The advancement of gene therapy has been slowed, in part, by inefficient transduction of targeted cells and poor long-term engraftment of genetically modified cells. Thus, the ability to select for a desired population of cells within a recipient would be of great benefit for improving gene therapy. Proposed strategies for in vivo cell selection using drug resistance genes have had disappointing outcomes and/or require highly genotoxic medications to be effective. We hypothesized that resistance to purine analogs, a well-tolerated, relatively low-toxicity class of medications, could be provided to cells using interfering RNA against hypoxanthine phosphoribosyl transferase. Using a lentiviral vector, we found that interfering RNA-mediated purine analog resistance (iPAR) provided relative resistance to 6-thioguanine (6TG) in murine hematopoietic cells compared with control- and untransduced cells. iPAR attenuated 6TG-induced G(2)/M checkpoint activation, cell-cycle arrest, and apoptosis. Furthermore, in recipients of transplanted bone marrow cells with iPAR, treatment with 6TG resulted in increased percentages of transduced peripheral blood cells and hematopoietic progenitor cells in the bone marrow. Secondary transplantations resulted in higher hematopoietic contributions from 6TG-treated primary recipients relative to phosphate-buffered saline-treated recipients. These findings indicate that iPAR/6TG can be used for in vivo hematopoietic progenitor cell selection.
The CAP Superfamily: Cysteine-Rich Secretory Proteins, Antigen 5, and Pathogenesis-Related 1 Proteins—Roles in Reproduction, Cancer, and Immune Defense (2008)

The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily members are found in a remarkable range of organisms spanning each of the animal kingdoms. Within humans and mice, there are 31 and 33 individual family members, respectively, and although many are poorly characterized, the majority show a notable expression bias to the reproductive tract and immune tissues or are deregulated in cancers. CAP superfamily proteins are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumor suppressor or prooncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilization. This review describes mammalian CAP superfamily gene expression profiles, phylogenetic relationships, protein structural properties, and biological functions, and it draws into focus their potential role in health and disease. The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. We conclude that overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters target specificity and, therefore, the biological consequences.
Observation of reduced boron penetration and gate depletion for poly-Si/sub 0.8/Ge/sub 0.2/ gated PMOS devices (1999)

Poly-Si/sub 0.8/Ge/sub 0.2/-and poly-Si-gated PMOS capacitors with very thin gate oxides were fabricated. Boron penetration and poly-gate depletion effects (PDE) in these devices were both analyzed. Observations of smaller flat-band voltage shift and superior gate oxide reliability suggest less boron penetration problem in poly-Si/sub 0.8/Ge/sub 0.2/-gated devices. Higher dopant activation rate, higher active dopant concentration near the poly/SiO/sub 2/ interface and therefore improved PDE were also found in boron-implanted poly-Si/sub 0.8/Ge/sub 0.2/-gated devices as compared to poly-Si-gated devices. A larger process window therefore exists for a poly-Si/sub 0.8/Ge/sub 0.2/ gate technology with regard to the tradeoff between boron penetration and poly-gate depletion.
fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans. (1988)

This paper describes the isolation and characterization of 16 mutations in the germ-line sex determination gene fog-2 (fog for feminization of the germ line). In the nematode Caenorhabditis elegans there are normally two sexes, self-fertilizing hermaphrodites (XX) and males (XO). Wild-type XX animals are hermaphrodite in the germ line (spermatogenesis followed by oogenesis), and female in the soma. fog-2 loss-of-function mutations transform XX animals into females while XO animals are unaffected. Thus, wild-type fog-2 is necessary for spermatogenesis in hermaphrodites but not males. The fem genes and fog-1 are each essential for specification of spermatogenesis in both XX and XO animals. fog-2 acts as a positive regulator of the fem genes and fog-1. The tra-2 and tra-3 genes act as negative regulators of the fem genes and fog-1 to allow oogenesis. Two models are discussed for how fog-2 might positively regulate the fem genes and fog-1 to permit spermatogenesis; fog-2 may act as a negative regulator of tra-2 and tra-3, or fog-2 may act positively on the fem genes and fog-1 rendering them insensitive to the negative action of tra-2 and tra-3.
The Valuation of Distressed Companies - A Conceptual Framework (2006)

It is often crucial to ascertain the value of a distressed company. Those interested in the company’s undertaking require this information to determine what should be done with the company’s business, and how the value in the company’s estate should be distributed amongst them. In this article, addressed primarily to the parties to corporate reorganisation proceedings in the UK and their advisers, we provide a conceptual framework within which these questions might be answered.\nThe first part of the article identifies the bases on which a company’s business might be valued. Drawing upon economic theory, empirical evidence, and the sophisticated principles evolved by US courts with long experience of dealing with such issues, it explains the circumstances in which one or other of these bases might appropriately be adopted. The onset of corporate distress creates unique additional problems in attempting business valuations, whether carried out in a court context or out of court. Focusing particularly on the incentives of those interested in the outcome of reorganisation proceedings, the article seeks to distinguish between the ‘structural’ and the ‘strategic’ factors giving rise to these problems, and explains how these might impact upon the valuation process. It then draws on the US jurisprudence on business valuation to outline three methods for putting a value on a ‘going concern’. It is submitted that the principles developed by US courts will prove helpful and persuasive as UK courts grapple more and more frequently with valuation issues. The second part of the article consists of a detailed analysis of the recent judgment of the English High Court in In re MyTravel Group Plc, which is employed as a case study in the application of the conceptual framework laid down in the first part.
Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41 (2008)

The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-/- and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.
RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase. (1992)

High-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution of ligands by exponential enrichment) from RNA populations randomized at 32 positions. Analysis of these ligands revealed a pseudoknot consensus with primary sequence bias at some positions. We demonstrated that at least one of the ligands inhibits cDNA synthesis by HIV reverse transcriptase but fails to inhibit other reverse transcriptases. These experiments highlight the power of SELEX to yield highly specific ligands that reduce the activity of target proteins. Such ligands may provide therapeutic reagents for viral and other diseases.
Animal Models for Medical Countermeasures to Radiation Exposure (2010)

Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the "Animal Rule" from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings.
Cell Cycle-dependent Regulation of Mammalian Ribonucleotide (1984)

Ribonucleotide reductase in mammalian cells is composed of two nonidentical subunits, proteins M1 and M2. Protein M2 contains a tyrosyl free radical, essential for activity, which can be quantified directly in frozen, packed cells by EPR spectroscopy. A 3-7-fold increase in the concentration of tyrosyl radical-containing M2 subunit was observed when mouse mammary tumor TA 3 cells passed from the GI to the S phase of the cell cycle. Similar results were obtained with cells synchronized by isoleucine starvation or separated by centrifugal elutriation. Addition of deuterated tyrosine to cells gives rise to a different EPR signal in newly synthesized protein M2. Pulse-chase experiments with deuterated tyrosine showed unequivocally that the S phase-correlated increase in radical-containing M2 subunit was due to de nouo protein synthesis. Labeled M2 molecules disappeared with a half-life of 3 h, and therefore new molecules must be synthesized at a high rate during the S phase. In contrast, after hydroxyurea inactivation, cells rapidly regenerated the tyrosyl radical in already existing protein M2 molecules. This enzyme activation mechanism is clearly different from the one responsible for regulating protein M2 activity during the cell cycle.
Si-ULSI with a scaled down future (1998)

Semiconductor technology in the 21st century will undergo major changes due to the significant material, engineering, and fundamental limits being approached as a consequence of scaling. Lithography is anticipated to undergo a radical change from optical to nonoptical. Device architecture and interconnects are also expected to undergo major changes in materials, structure, and fabrication technology.
Oxygen adsorption on well-defined gold particles on TiO2(110) (1999)

Very tiny Au particles on TiO2 show excellent activity and selectivity in a number of oxidation reactions. We have studied the vapor deposition of Au onto a TiO2(110) surface using x-ray photoelectron spectroscopy, low energy ion scattering, low energy electron diffraction, and temperature programmed description (TPD) and found that we can prepare Au islands with controlled thicknesses from one to several monolayers. In order to understand at the atomic level the unusual catalytic activity in oxidation reactions of this system, we have studied oxygen adsorption on Au/TiO2(110) as a function of Au island thickness. A hot filament was used to dose gaseous oxygen atoms, since O2 gas does not readily dissociatively adsorb on Au. The saturation coverage of oxygen adatoms on Au particles approaches 1.0 ML, similar to that found on bulk Au(110) and (111). TPD results show higher desorption temperatures (645 K) for ultrathin gold particles on TiO2(110) than thicker particles (520–545 K). This implies that Oa bonds much more strongly to ultrathin islands of Au. Thus from Brönsted relations, ultrathin gold particles should be able to dissociatively adsorb O2 more readily than thick gold particles. We postulate that the catalytic activity in oxidation reactions demonstrated by thin (small) Au particles on TiO2 is related to the positive influence this stronger bonding to oxygen has on the dissociative adsorption rate of O2. © 1999 American Vacuum Society.
Emerging coronaviruses: Genome structure, replication, and pathogenesis (2020)

The recent emergence of a novel coronavirus (2019-nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.
Continuous monitoring of cortical perfusion by laser Doppler flowmetry in ventilated patients with head injury. (1994)

A method for monitoring cortical perfusion by laser Doppler flowmetry (LDF) in the neurointensive care unit is described. Out of 22 patients with head injuries, reliable and long term recordings were obtained in 16. Laser Doppler flowmetry registered changes in cortical microcirculatory flow in response to spontaneous waves of raised intracranial pressure, and to therapeutic manoeuvres that altered the cerebral perfusion pressure. Comparisons of variations in flux signal with cerebral perfusion pressure provided an indication of the autoregulatory state of the cortical microcirculation, and analysis of raw LDF data demonstrated an autoregulatory breakpoint of cerebral perfusion pressure of 58 mm Hg, below which cortical perfusion failed. Although middle cerebral artery flow velocities were generally tightly coupled with LDF signal changes, episodes of uncoupling were seen. The potential uses and limitations of LDF in the neurointensive care setting are discussed.