gebhart/patrepeval huggingface dataset:
Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review (2002)

This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to 100%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes.
EXPANDING THE GENETIC CODE (2006)

Recently, a general method was developed that makes it possible to genetically encode unnatural amino acids with diverse physical, chemical, or biological properties in Escherichia coli, yeast, and mammalian cells. More than 30 unnatural amino acids have been incorporated into proteins with high fidelity and efficiency by means of a unique codon and corresponding tRNA/aminoacyl-tRNA synthetase pair. These include fluorescent, glycosylated, metal-ion-binding, and redox-active amino acids, as well as amino acids with unique chemical and photochemical reactivity. This methodology provides a powerful tool both for exploring protein structure and function in vitro and in vivo and for generating proteins with new or enhanced properties.
A complex pattern of translational initiation and phosphorylation in L-myc proteins. (1991)

Molecular analysis of the human proto-oncogene L-myc revealed a complex pattern of gene expression including alternative splicing and polyadenylation site selection of mRNA, giving rise to at least four mRNAs. These mRNAs in turn can code for several proteins. In this report, we characterize and define the origins of the major L-myc proteins. In vitro translation revealed that (i) two L-myc proteins (p59 and p65) were derived through alternative translational initiation at a non-AUG (CUG) site in intron 1 and at an AUG site in exon 2 of L-myc, and that (ii) extensive post-translational phosphorylation of these proteins yielded three additional proteins (p60, p66, and p68). Transfection experiments in rat embryo cells revealed the in vivo existence of this unusual CUG-initiated protein and demonstrated that it possessed transforming activity. Further, immuno-precipitation using high titered anti-L-myc peptide antisera, of two L-myc expressing small-cell lung cancer cell lines revealed three major L-myc proteins (p60, p66 and p68) all of which were derived from extensive phosphorylation of a p59 protein.
Biogeochemical, Health, and Ecotoxicological Perspectives on Gold and Gold Mining (2004)

Despite the esteemed nature of gold in society, evidence of adverse ecotoxicological effects and risk to human health in various mining and extraction techniques has generated increasing interest in the biological and environmental implications of gold. Biogeochemical, Health, and Ecotoxicological Perspectives on Gold and Gold Mining is the first c
Influence of L-type Ca channel alpha 2/delta-subunit on ionic and gating current in transiently transfected HEK 293 cells (1996)

We have measured ionic and gating currents in human embryonic kidney (HEK 293) cells transiently transfected with cDNAs encoding subunits of the cardiac voltage-gated L-type Ca2+ channel. Robust recombinant ionic current and associated nonlinear charge movement could be measured over a broad voltage range without contamination by endogenous channel activity. Coexpression of the alpha 2/delta-subunit along with alpha 1- and beta 2-subunits speeded activation and deactivation kinetics and significantly increased the maximal conductance of ionic current. Charge movement was measured at voltages negative to the threshold for activation of ionic current, and gating charge could be immobilized at positive holding potentials that did not inactivate ionic current. The ratio of maximal ionic conductance to maximal charge moved remained the same in the absence or presence of the alpha 2/delta-subunit. However, the maximal amount of charge moved was increased about twofold in the presence of the alpha 2/delta-subunit. These results suggest that coexpression of the alpha 2/delta-subunit enhances the expression of functional L-type channels and, in addition, provide evidence that most of the L-type channel-associated nonlinear charge movement is caused by transitions between nonconducting states of the channel protein that precede the open and inactivated states.
Enzyme monolayer- and bilayer-modified tin oxide electrodes for the determination of hydrogen peroxide and glucose (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme monolayer- and bilayer-modified tin oxide electrodes for the determination of hydrogen peroxide and glucoseTetsu. Tatsuma, Yusuke. Okawa, and Tadashi. WatanabeCite this: Anal. Chem. 1989, 61, 21, 2352–2355Publication Date (Print):November 1, 1989Publication History Published online1 May 2002Published inissue 1 November 1989https://pubs.acs.org/doi/10.1021/ac00196a007https://doi.org/10.1021/ac00196a007research-articleACS PublicationsRequest reuse permissionsArticle Views704Altmetric-Citations154LEARN 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 Get e-Alerts
Expression of the oxytocin gene in the large cells of the bovine corpus luteum (1987)

In the bovine ovary there is a delay of 4-6 days between the observed maximum of oxytocin mRNA and the peak in the luteal levels of oxytocin nonapeptide. This implies a maturation process involving components of the post-translational processing pathway. In situ hybridization shows the oxytocin gene to be transcribed exclusively in the large cells of the corpus luteum at the beginning of the estrous cycle.
Toward the First Class of Suicide Inhibitors of Kallikreins Involved in Skin Diseases (2014)

The inhibition of kallikreins 5 and 7, and possibly kallikrein 14 and matriptase, (that initiates the kallikrein proteolytic cascade) constitutes an innovative way to treat some skin diseases such as Netherton syndrome. We present here the inhibitory properties of coumarin-3-carboxylate derivatives against these enzymes. Our small collection of these versatile organic compounds was enriched by newly synthesized derivatives in order to obtain molecules selective against one, two, three enzymes or acting on the four ones. We evidenced a series of compounds with IC50 values in the nanomolar range. A suicide mechanism was observed against kallikrein 7 whereas the inactivation was either definitive (suicide type) or transient for kallikreins 5 and 14, and matriptase. Most of these potent inhibitors were devoid of cytotoxicity toward healthy human keratinocytes. In situ zymography investigations on skin sections from human kallikrein 5 transgenic mouse revealed significant reduction of the global proteolytic activity by several compounds.
MicroRNAs and the regulation of fibrosis (2010)

MicroRNAs (miRNAs) are small, noncoding RNAs of 18-25 nucleotides that are generally believed to either block the translation or induce the degradation of target mRNA. miRNAs have been shown to play fundamental roles in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis and carcinogenesis. Fibrosis results from an imbalance in the turnover of extracellular matrix molecules and is a highly debilitating process that can eventually lead to organ dysfunction. A growing body of evidence suggests that miRNAs participate in the fibrotic process in a number of organs including the heart, kidney, liver and lung. In this review, we summarize our current understanding of the role of miRNAs in the development of tissue fibrosis and their potential as novel drug targets.
Refining the high-dose streptozotocin-induced diabetic non-human primate model: an evaluation of risk factors and outcomes (2011)

In preparation for islet transplantation, diabetes was induced using streptozotocin (STZ) in non-human primates ranging from juveniles to adults with diverse body types: we studied the process with respect to the diabetic state and emergence of adverse events (AEs) and their severity, and identified risk factors for clinical and laboratory AEs. Pharmaceutical-grade STZ was given based on body surface area (BSA) (1050-1250 mg/m(2), equivalent to 80-108 mg/kg) or on body weight (BW) (100 mg/kg) to 54 cynomolgus and 24 rhesus macaques. AEs were related to risk factors, i.e. obesity parameters, BW and BSA, age and STZ dose in mg/m(2). Clinical AEs during the first days after infusion prompted euthanasia of three animals. Except for those three animals, diabetes was successfully induced as shown by circulating C-peptide levels, the intravenous glucose tolerance test and/or arginine stimulation test. C-peptide after infusion weakly correlated (P = 0.048) with STZ dose in mg/m(2). Grade ≥3 nephrotoxicity or hepatotoxicity (serum markers >3× baseline or >5 × baseline, respectively) occurred in about 10% of cases and were generally mild and reversible. Grade ≥2 clinical AEs occurred in seven of 78 animals, reversed in four cases and significantly correlated with obesity parameters. Taking girth-to-height ratio (GHtR) as an indicator of obesity, with threshold value 0.92-0.95, the positive predictive value of obesity for AEs was 92% and the specificity 94%. We conclude that diabetes is successfully induced in non-obese animals using a 100 mg/kg pharmaceutical grade STZ dose. Obesity is a significant risk factor, and animals with a higher than normal GHtR should preferably receive a lower dose. The incidence of relevant clinical or laboratory AEs is low. Careful monitoring and supportive medical intervention can result in recovery of AEs.
Macromolecular changes caused by formalin fixation and antigen retrieval (2007)

Although the mechanics of formalin fixation and antigen retrieval have been studied extensively and reviewed periodically, little attention has been directed toward conformational changes in target molecules. Formaldehyde changes the shape of tissue molecules by appending small hydroxymethyl groups to them. These adducts, in turn, can react with other tissue molecules to form crosslinks, or they can participate in a variety of reactions during tissue processing, including formation of imines, ethoxymethyl adducts, and further crosslinks. Under the influence of alcohol dehydration, fixed DNA may fragment and form a variety of depurination products. The situation becomes even more complex with short fixation times because under these conditions, the dehydrating agent used for tissue processing denatures macromolecules in other ways, most notably through rearrangement of molecular shape to move hydrophobic realms outward and hydrophilic areas inward (hydrophobic inversions). How tissue molecules are modified affects the outcome of immunohistochemical staining and prospects for restoration of antigenicity. Immunoreacitivity may be compromised because epitopes are either sterically hidden, but otherwise unaffected, or they have been altered more directly. Enzyme-based retrieval methods are best suited for the former because they literally snip the molecule apart to reveal the portions of interest. Heat-induced retrieval with buffers can demodify affected epitopes by removing adducts and breaking crosslinks. The choice of temperature and pH is usually critical for optimal retrieval. Effective temperatures are directly related to the strength of bonds-higher temperatures are needed to break stronger bonds. The pH of the retrieval solution determines the charge on the tissue molecule; the goal is to create a charge that causes the demodified molecule to assume a near natural conformation. Rational use of these concepts should lead to better control of immunohistochemical reactions.
On multicarrier CDMA mobile radio systems with joint detection and coherent receiver antenna diversity (2002)

The combination of code division multiple access (CDMA) and multicarrier (MC) transmission techniques, termed MC-CDMA, is considered a promising alternative to conventional DS (direct sequence)-CDMA. An MC-CDMA concept which is well-suited for mobile radio applications is described. This concept overcomes the disadvantages of previously proposed concepts. In MC-CDMA mobile radio systems, signal reception is impaired by time-varying multipath propagation. The impairments can be reduced by coherent receiver antenna diversity (CRAD). The application of CRAD in combination with joint detection (JD) techniques to the more critical uplink of MC-CDMA mobile radio systems is investigated. Four JD techniques for CRAD are presented and their performance are studied.
Sequence Variants in the RNF212 Gene Associate with Genome-Wide Recombination Rate (2008)

The genome-wide recombination rate varies between individuals, but the mechanism controlling this variation in humans has remained elusive. A genome-wide search identified sequence variants in the 4p16.3 region correlated with recombination rate in both males and females. These variants are located in the RNF212 gene, a putative ortholog of the ZHP-3 gene that is essential for recombinations and chiasma formation in Caenorhabditis elegans. It is noteworthy that the haplotype formed by two single-nucleotide polymorphisms (SNPs) associated with the highest recombination rate in males is associated with a low recombination rate in females. Consequently, if the frequency of the haplotype changes, the average recombination rate will increase for one sex and decrease for the other, but the sex-averaged recombination rate of the population can stay relatively constant.
Correlation analysis of Baker's studies on enzyme inhibition. 2. Chymotrypsin, trypsin, thymidine phosphorylase, uridine phosphorylase, thymidilate synthetase, cytosine nucleoside deaminase, dihydrofolate reductase, malate, glutamate, lactate, and glyceraldehyde-phosphate dehydrogenase (1976)

The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to suggest special enzyme-ligand interactions. Several examples are given of the use of correlation equations in comparing structural features of different systems.
Efficient engineering of a bacteriophage genome using the type I-E CRISPR-Cas system (2014)

The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system has recently been used to engineer genomes of various organisms, but surprisingly, not those of bacteriophages (phages). Here we present a method to genetically engineer the Escherichia coli phage T7 using the type I-E CRISPR-Cas system. T7 phage genome is edited by homologous recombination with a DNA sequence flanked by sequences homologous to the desired location. Non-edited genomes are targeted by the CRISPR-Cas system, thus enabling isolation of the desired recombinant phages. This method broadens CRISPR Cas-based editing to phages and uses a CRISPR-Cas type other than type II. The method may be adjusted to genetically engineer any bacteriophage genome.
AIDS and glycosylation (1990)

Journal Article AIDS and glycosylation Get access Ten Feizi, Ten Feizi 1 Glycoconjugates Section, MRC Clinical Research CentreHarrow, Middlesex HA1 3UJ, UK 1To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Margot Larkin Margot Larkin Glycoconjugates Section, MRC Clinical Research CentreHarrow, Middlesex HA1 3UJ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Glycobiology, Volume 1, Issue 1, September 1990, Pages 17–23, https://doi.org/10.1093/glycob/1.1.17 Published: 01 September 1990 Article history Received: 15 August 1990 Accepted: 15 August 1990 Published: 01 September 1990
Transcriptome sequencing and annotation of the microalgae Dunaliella tertiolecta: Pathway description and gene discovery for production of next-generation biofuels (2011)

The construction of metabolic pathways involved in the biosynthesis and catabolism of fatty acids, triacylglycrols, and starch in D. tertiolecta as well as the assembled transcriptome provide a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock.
A new power amplifier topology with series biasing and power combining of transistors (2003)

A power amplifier topology was demonstrated in a microwave monolithic integrated circuit (MMIC) implementation with GaAs MESFETs. This topology overcomes several limitations of the traditional approach of paralleling of power transistor unit cells. In the new topology, unit cells are both parallel and series combined. The benefits include higher input and output impedances, broadband power matched interstage networks, and high voltage biasing at reduced DC current. Measured results on a MMIC and a hybrid power amplifier implemented with this technique are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cultivation of Human Embryonic Stem Cells Without the Embryoid Body Step Enhances Osteogenesis In Vitro (2005)

Osteogenic cultures of embryonic stem cells (ESCs) are predominately derived from three-dimensional cell spheroids called embryoid bodies (EBs). An alternative method that has been attempted and merits further attention avoids EBs through the immediate separation of ESC colonies into single cells. However, this method has not been well characterized and the effect of omitting the EB step is unknown. Herein, we report that culturing human embryonic stem cells (hESCs) without the EB stage leads to a sevenfold greater number of osteogenic cells and to spontaneous bone nodule formation after 10-12 days. In contrast, when hESCs were differentiated as EBs for 5 days followed by plating of single cells, bone nodules formed after 4 weeks only in the presence of dexamethasone. Furthermore, regardless of the inclusion of EBs, bone matrix formed, including cement line matrix and mineralized collagen, which displayed apatitic mineral (PO4) with calcium-to-phosphorous ratios similar to those of hydroxyapatite and human bone. Together these results demonstrate that culturing hESCs without an EB step can be used to derive large quantities of functional osteogenic cells for bone tissue engineering.
Product Differentiation and Market Segmentation as Alternative Marketing Strategies (1956)

URING the decade of the 1930's, the work of Robinson and Chamberlin resulted in a revitalization of economic theory. While classical and neoclassical theory provided a useful framework for economic analysis, the theories of perfect competition and pure monopoly had become inadequate as explanations of the contemporary business scene. The theory of perfect competition assumes homogeneity among the components of both the demand and supply sides of the market, but diversity or heterogeneity had come to be the rule rather than the exception. This analysis reviews major marketing strategy alternatives that are available to planners and merchandisers of products in an environment characterized by imperfect competition.
Interferon-γ Induces Human Vascular Smooth Muscle Cell Proliferation and Intimal Expansion by Phosphatidylinositol 3-Kinase–Dependent Mammalian Target of Rapamycin Raptor Complex 1 Activation (2007)

Interferon (IFN)-gamma, a cytokine characteristically expressed in arteriosclerotic diseases, acts directly on vascular smooth muscle cells to induce cellular proliferation and intimal expansion. Signaling by the mammalian target of rapamycin raptor complex, known as mTORC1, is associated with cell growth and is active within arteriosclerotic lesions but is not known to be triggered by proinflammatory factors in vascular smooth muscle cells. We investigated the mechanisms for the proarteriosclerotic effects of IFN-gamma in the absence of leukocytes by exploiting the species specificity of this cytokine in a chimeric model of immunodeficient mouse recipients bearing human coronary artery grafts and intravenously inoculated with adenovirus encoding a human IFN-gamma transgene. We found that IFN-gamma-mediated vascular smooth muscle cell proliferation and intimal expansion were associated with phosphorylation of the mTORC1 effector ribosomal protein S6 kinase 1, that the graft morphological changes and S6 kinase 1 activation were inhibited by the mTORC1 inhibitor rapamycin in vivo, and that IFN-gamma-induced mTORC1 signaling was dependent on phosphatidylinositol 3-kinase activity under serum-free conditions in vitro. Our work establishes an immunologic stimulus for mTORC1 signaling in vascular smooth muscle cells, emphasizes that mTORC1 activation is critical in immune-mediated vascular remodeling, and provides further mechanistic insight into the successful clinical application of rapamycin therapy for atherosclerosis and graft arteriosclerosis.