gebhart/patrepeval huggingface dataset:
Programmed DNA destruction by miniature CRISPR-Cas14 enzymes (2018)

CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools use RNA-guided Cas proteins whose large size (950 to 1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400 to 700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements. Moreover, target recognition by Cas14 triggers nonspecific cutting of ssDNA molecules, an activity that enables high-fidelity single-nucleotide polymorphism genotyping (Cas14-DETECTR). Metagenomic data show that multiple CRISPR-Cas14 systems evolved independently and suggest a potential evolutionary origin of single-effector CRISPR-based adaptive immunity.
Experimental Study of Intervertebral Disc Allografting in the Dog (1994)

More investigation of storage methods is needed to enhance the viability of the intervertebral disc for successful intervertebral disc allografting.
Estrogen Rapidly Attenuates a GABA<sub>B</sub> Response in Hypothalamic Neurons (1996)

GABA is a predominant neurotransmitter in the hypothalamus and an important regulator of hypothalamic function. To elucidate the cellular basis for GABAergic action in this region, we used intracellular recordings from identified hypothalamic neurons. Ninety-three percent of the mediobasal hypothalamic neurons responded to GABAB receptor stimulation, and the presence of bicuculline-sensitive synaptic potentials indicated a tonic, GABAA receptor-mediated input. Stimulation of GABAB receptors hyperpolarized these cells by activating an inwardly rectifying potassium conductance. We characterized GABAB responses by generating concentration-response curves to the GABAB agonist baclofen. There was heterogeneity in the responses to baclofen, with one third of the cells having low baclofen potency (EC50 = 5.0 microM). Two thirds of the neurons had a 4-fold higher potency (EC50 = 1.2 microM), larger somas and a more lateral distribution. Previous work has shown that hypothalamic GABAB and mu-opioid receptors open the same K+ channels and that the response to mu-opioid agonists is rapidly attenuated by 17 beta-estradiol (E2). In order to test the hypothesis that the coupling of GABAB receptors to K+ channels is also altered, baclofen concentration-response curves were generated before and after an E2 challenge (100 nM, 20 min). Consistent with our hypothesis, the potency of baclofen was decreased nearly 4-fold in a subset of the cells that had a high potency response to baclofen. Furthermore, decreased baclofen potency only occurred in those cells in which E2 also altered the mu-opioid responses. Therefore, our findings suggest that a discrete subpopulation of hypothalamic neurons is sensitive to estrogen actions to alter inhibitory transmission. We propose that the alteration of GABAB and mu-opioid input is consistent with estrogen's rapid inhibition of the reproductive axis.
Core‐shell type polymer microspheres prepared by domain fixing of block copolymer films (1989)

Abstract Well‐defined poly[styrene(S)‐b‐isoprene(I)] diblock copolymers were prepared by sequential anionic addition. The crosslinking reactions of polyisoprene (PI) spherical domains of these block copolymers were carried out in a n ‐hexane solution of sulfur monochloride (S 2 Cl 2 ). Electron micrograph of crosslinked products indicates the structure of core‐shell type polymer microspheres. It is found from NMR and turbi+imetric measurements that the solubility of core‐shell type polymer microspheres depends strongly on that of block chains comprising the shell portion. The particle size of these microspheres shows a narrow distribution.
Transition metal-catalyzed radical cyclizations: a low-temperature process for the cyclization of N-protected N-allyltrichloroacetamides to trichlorinated .gamma.-lactams and application to the stereoselective preparation of .beta.,.gamma.-disubstituted .gamma.-lactams (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransition metal-catalyzed radical cyclizations: a low-temperature process for the cyclization of N-protected N-allyltrichloroacetamides to trichlorinated .gamma.-lactams and application to the stereoselective preparation of .beta.,.gamma.-disubstituted .gamma.-lactamsHideo Nagashima, Nobuyasu Ozaki, Masayuki Ishii, Koji Seki, Masayoshi Washiyama, and Kenji ItohCite this: J. Org. Chem. 1993, 58, 2, 464–470Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/jo00054a034https://doi.org/10.1021/jo00054a034research-articleACS PublicationsRequest reuse permissionsArticle Views1150Altmetric-Citations120LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Anti-AMP antibody precipitation of multiply adenylylated forms of glutamine synthetase from Escherichia coli: a model relating both concentration and density of antigenic sites with the antibody-antigen interaction. (1980)

Sheep antibodies directed against an AMP-bovine serum albumin conjugate exhibit highly specific binding toward AMP. These antibodies bind to the AMP moiety of adenylylated glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] from Escherichia coli and to no other antigenic determinant on the protein. E coli glutamine synthetase can exist in variously modified (isomeric) forms that differ with respect to the number (0-12) and the distribution of identically adenylylated subunits [Ciardi, J. E., Cimino, F. &amp; Stadtman, E. R. (1973) biochemistry 12, 4321-4330]. Using this enzyme, together with the AMP-specific antibodies, we have investigated the effects of the total concentration, population density, and topographical distribution of multiple identical antigenic determinants on the antigen-antibody interaction. Stopped flow fluorescence measurements show that the rate and extent of initial binding of the antibodies to the antigen are a function of the total concentration of AMP groups and are independent of the number of AMP groups der dodecamer. However, the rate of lattice formation increases with increasing epitope density, and the maximal amount of glutamine synthetase precipitated is directly proportional to the average number of adenylylated subunits per dodecamer. The data suggest that partially adenylylated enzyme preparations are composed of subpopulations of glutamine synthetase molecules that differ in their tendency to form precipitable aggregates, due presumably to differences in the topographical distribution of antigenic determinants on the surface of the enzyme. The enzyme species that form soluble immune complexes do so possibly due to intramolecular crosslinkage of the bivalent antibodies with adenylylated subunits to the exclusion of intermolecular crosslinkage.
Biochemical and Structural Insights into Bacterial Organelle Form and Biogenesis (2008)

Many heterotrophic bacteria have the ability to make polyhedral structures containing metabolic enzymes that are bounded by a unilamellar protein shell (metabolosomes or enterosomes). These bacterial organelles contain enzymes associated with a specific metabolic process (e.g. 1,2-propanediol or ethanolamine utilization). We show that the 21 gene regulon specifying the pdu organelle and propanediol utilization enzymes from Citrobacter freundii is fully functional when cloned in Escherichia coli, both producing metabolosomes and allowing propanediol utilization. Genetic manipulation of the level of specific shell proteins resulted in the formation of aberrantly shaped metabolosomes, providing evidence for their involvement as delimiting entities in the organelle. This is the first demonstration of complete recombinant metabolosome activity transferred in a single step and supports phylogenetic evidence that the pdu genes are readily horizontally transmissible. One of the predicted shell proteins (PduT) was found to have a novel Fe-S center formed between four protein subunits. The recombinant model will facilitate future experiments establishing the structure and assembly of these multiprotein assemblages and their fate when the specific metabolic function is no longer required.
Localization of the Ethylene Receptor ETR1 to the Endoplasmic Reticulum of Arabidopsis (2002)

The ethylene receptor ETR1 of Arabidopsis contains transmembrane domains responsible for ethylene binding and membrane localization. Sequence analysis does not provide information as to which membrane system of the plant cell ETR1 is localized. Examination by aqueous two-phase partitioning, sucrose density-gradient centrifugation, and immunoelectron microscopy indicates that ETR1 is predominantly localized to the endoplasmic reticulum. Localization of ETR1 showed no change following a cycloheximide chase. Ethylene binding by ETR1 did not affect localization to the endoplasmic reticulum, based upon analysis of plants treated with the ethylene precursor 1-aminocyclopropane- 1-carboxylic acid and by examination of a mutant receptor that does not bind ethylene. Determinants within the amino-terminal half of ETR1 are sufficient for targeting to and retention at the endoplasmic reticulum. These data support a central role of the plant endoplasmic reticulum in hormone perception and signal transduction.
Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer (2015)

Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone. (Funded by Pfizer; PALOMA3 ClinicalTrials.gov number, NCT01942135.).
Laminar flow through microchannels used for microscale cooling systems (2002)

Microchannel cooling is one the prospective microscale cooling methods that can meet future needs. Many theoretical and experimental studies have been reported in the past decade. This paper presents an experimental study on the laminar flow of liquid through microchannels with different cross-sections. The experimental results for circular micropipes agree well with theoretical predictions for conventional ducts. The values of fRe (Darcy friction factor-Reynolds number product) for laminar flow of liquid in the silicon microchannels with noncircular cross-sections are smaller than those of the conventional values. The surface roughness of the silicon microchannels fabricated by surface and bulk micromachining processes is also measured. The turbulent flow and heat transfer characteristics in microchannels are to be studied in the next phase of research.
Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. (1996)

T lymphocytes and monocyte/macrophages are prominent components of atherosclerotic lesions, and many of these cells are activated and secreting cytokines. To determine the role of these cells in the pathogenesis of atherosclerosis, we studied its development in T-cell-deficient mice fed a high fat atherogenic diet. Depleting euthymic mice of their CD4+ lymphocytes by 20 weekly injections of CD4 monoclonal antibodies reduced the mean area of their aortic lesions by approximately 70%. Similarly, the mean lesion area of T-cell-deficient nude (nu/nu) mice was 10% of the size of that of their heterozygote (nu/+) litter mates. Flow cytometric studies of splenic T cells and analyses of serum total and HDL cholesterol of these mice indicated that the differences in mean lesion areas among the experimental groups were most closely correlated with differences in splenic T cells content. These studies suggest that in these two models T lymphocytes contribute to the pathogenesis of early atherosclerotic lesions and that a further understanding of this phenomenon may provide future approaches toward the prevention and treatment of the disease.
Expression of Human Polyspecific Renal Organic Cation Transport Activity in Xenopus laevis Oocytes (1997)

Polyspecific organic cation transporters in the basolateral and brush border membrane of the kidney play a role in the elimination of many clinically important drugs and endogenous compounds. In this study we report the functional expression of organic cation transport activity in Xenopus laevis oocytes injected with poly(A)+RNA (mRNA) isolated from human kidney. Uptake of [14C]tetraethylammonium (TEA) was measured in mRNA-injected or water-injected oocytes, 4 days after injection. In oocytes injected with 50 ng of mRNA isolated from human renal cortex, the uptake of [14C]TEA was significantly increased in comparison with water-injected oocytes (7.2 +/- 0.6 and 3.5 +/- 0.3 pmol/oocyte/h, respectively). Injection of 20 ng of an enriched size-fraction (fraction C) of mRNA (mean size of 2.3 kb) resulted in further enhancement of [14C]TEA uptake: [14C]TEA uptake was enhanced six-to seven-fold in oocytes injected with fraction C (23.7 +/- 3.7 pmol/oocyte/h) in comparison with water-injected oocytes. The uptake of TEA in mRNA-injected oocytes was significantly inhibited by 5 mM of unlabeled TEA, cimetidine, and N1-methylnicotinamide. These data suggest that polyspecific organic cation transport activity can be successfully expressed in Xenopus laevis oocytes injected with mRNA isolated from human kidney.
Cognitive function as an emerging treatment target for marijuana addiction. (2010)

Cannabis is the most widely used illicit substance in the world, and demand for effective treatment is increasing. However, abstinence rates following behavioral therapies have been modest, and there are no effective pharmacotherapies for the treatment of cannabis addiction. We propose a novel research agenda and a potential treatment strategy, based on observations that both acute and chronic exposure to cannabis are associated with dose-related cognitive impairments, most consistently in attention, working memory, verbal learning, and memory functions. These impairments are not completely reversible upon cessation of marijuana use, and moreover may interfere with the treatment of marijuana addiction. Therefore, targeting cognitive impairment associated with chronic marijuana use may be a promising novel strategy for the treatment of marijuana addiction. Preclinical studies suggest that medications enhancing the cholinergic transmission may attenuate cannabis-induced cognitive impairments, but these cognitive enhancing medications have not been examined in controlled human studies. Preliminary evidence from individuals addicted to other drugs suggests that computerized cognitive rehabilitation may also have utility to improve cognitive function in marijuana users. Future clinical studies optimally designed to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these treatments for marijuana addiction.
Pharmacokinetics and metabolism of selected prodrugs of PMEA in rats. (1997)

The oral bioavailability of PMEA [9-[2-(phosphonomethoxy)ethyl]adenine; adefovir) has been determined in rats from three bisester prodrugs of PMEA: bis-(pivaloyloxymethyl) PMEA (bis-POM PMEA), bis-(phenyl) PMEA, and bis-(o-ethoxyphenyl) PMEA. The prodrugs were each administered to 9 male rats as solutions in PEG 400 at a dose of 10 mg-equivalent of PMEA per kg. Plasma samples were obtained over the course of 12 hr and concentrations of PMEA were determined by fluorescence derivatization and analysis by HPLC. Concentrations of PMEA observed in plasma following oral administration of PMEA prodrugs were compared with levels observed for intravenous PMEA. The observed oral bioavailabilities of PMEA from bis-POM PMEA, bis-(phenyl) PMEA, and bis-(o-ethoxyphenyl) PMEA were 38.2%, 2.46%, and 40.1%, respectively. PMEA was the only metabolite formed after oral administration of bis-POM PMEA. Three metabolites were detected after oral administration of either bis-(phenyl) PMEA or bis-(o-ethoxyphenyl) PMEA to rats: PMEA, the corresponding monoester, and 2-adenylacetic acid. The major metabolite of bis-(phenyl) PMEA was 2-adenylacetic acid following oral administration. 2-Adenylacetic acid appears to have been formed from the intact prodrugs by a P450 mediated oxidation of the ethyl side chain.
A Regulated DC-DC Voltage Source Converter Using a High Frequency Link (1982)

Power converters which employ a high frequency (HF) link possess several attractive features such as reduced size of reactive components, fast response, and ease of commutation. Either series or parallel connection of the load to the link capacitor can be employed by such converters. Converters that have a series link capacitor-load configuration are seen by the load as a current source. A dc-dc converter which uses a parallel link capacitor-load configuration is investigated. The output dc voltage is regulated by varying the link frequency. Such a converter behaves as a voltage source and is suitable for voltage source inverter applications. The converter is analyzed. Based on the analysis, a design procedure is given. A control scheme is outlined. Results from a prototype converter are presented.
Integrating Navigation with Search (2009)

This chapter describes interfaces to support navigation (or browsing) as part of the search process. Chapter 3 discusses theoretical models of browsing versus search as information seeking strategies, as well as the notion of information scent and information architecture. As mentioned there, one way to distinguish searching versus browsing is to note that search queries tend to produce new, ad hoc collections of information that have not been gathered together before, whereas navigation/browsing refers to selecting links or categories that produce pre-defined groups of information items. Browsing activities can also include following a chain of links, switching from one view to another, in a sequence of scan and select operations. Browsing can also refer to the casual, mainly undirected exploration of navigation structures.
CD8+ T cell infiltration in breast and colon cancer: A histologic and statistical analysis (2018)

The prevalence of cytotoxic tumor infiltrating lymphocytes (TILs) has demonstrated prognostic value in multiple tumor types. In particular, CD8 counts (in combination with CD3 and CD45RO) have been shown to be superior to traditional UICC staging in colon cancer patients and higher total CD8 counts have been associated with better survival in breast cancer patients. However, immune infiltrate heterogeneity can lead to potentially significant misrepresentations of marker prevalence in routine histologic sections. We examined step sections of breast and colorectal cancer samples for CD8+ T cell prevalence by standard chromogenic immunohistochemistry to determine marker variability and inform practice of T cell biomarker assessment in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Stained sections were digitally imaged and CD8+ lymphocytes within defined regions of interest (ROI) including the tumor and surrounding stroma were enumerated. Statistical analyses of CD8+ cell count variability using a linear model/ANOVA framework between patients as well as between levels within a patient sample were performed. Our results show that CD8+ T-cell distribution is highly homogeneous within a standard tissue sample in both colorectal and breast carcinomas. As such, cytotoxic T cell prevalence by immunohistochemistry on a single level or even from a subsample of biopsy fragments taken from that level can be considered representative of cytotoxic T cell infiltration for the entire tumor section within the block. These findings support the technical validity of biomarker strategies relying on CD8 immunohistochemistry.
Stages of B cell differentiation in human lymphoid tissue. (1981)

Monoclonal antibodies reactive with B cell-specific differentiation and other antigens were used to investigate stages of B cell maturation in human lymphoid tissue, using an immunoperoxidase technique on frozen tissue sections. Lymphoid follicles, which represent the major anatomic compartment of B cells, demonstrated cellular antigenic expressions that appear to reflect differentiation of B cells. The majority of cells in the primary follicles and the mantle zones of secondary follicles expressed surface antigens similar to those of circulating B cells, namely IgM, IgD, Ia, B1, and B2. In contrast, the germinal center cells of secondary follicles stained for IgM, IgG, B1, B2, and Ia antigens, but not for IgD, and furthermore, acquired the T10 antigen. The germinal centers stained much more intensely than mantle zones with anti-B2, whereas no such striking difference in the staining intensity was observed with anti B1. Plasma cells, which represent the end stage of B cell differentiation, showed intense cytoplasmic staining with the anti-T10 antibody. The results indicate that the generation of germinal center cells in primary lymphoid follicles involves phenotype changes that correspond largely to those previously observed after both antigenic and mitogenic activation of B lymphocytes.
Iron-Overload–Related Disease inHFEHereditary Hemochromatosis (2008)

In persons who are homozygous for the C282Y mutation, iron-overload-related disease developed in a substantial proportion of men but in a small proportion of women.
The 20,000 molecular weight variant of human growth hormone. Preparation and some physical and chemical properties. (1981)

Extracts of frozen human pituitary glands contain, in addition to normal growth hormone (hGH (Mr = 22,005), a variant of lower molecular weight (approximately 20,000) (Singh, R. N. P., Seavey, B. K. and Lewis, U. J. (1974) Endocrinol. Res. Commun. 1, 449-464). This material, designated 20K hGH, occurs in various forms with the majority present as a heterologous dimer of Mr = 20,000 hGH and hGH. The purification scheme for obtaining the variant from these fractions is described. Analysis of Mr = 20,000 hGH in the sequenator has confirmed that residues 32-46 of hGH are absent in Mr = 20,000 hGH. The structures of hGH and Mr = 20,000 hGH have been compared by 1H nuclear magnetic resonance spectroscopy, circular dichroism, spectrophotometric titration, and nitration of the tyrosine residues by tetranitromethane. The results indicate that the folding of the polypeptide chain of the two proteins is similar but not identical.