gebhart/patrepeval huggingface dataset:
Significance of the immune response to a major, conformational B-cell epitope on the hepatitis C virus NS3 region defined by a human monoclonal antibody (1994)

The nonstructural protein NS3 of hepatitis C virus (HCV) possesses two enzymatic domains which are thought to be essential for the virus life cycle: an N-terminal serine-type proteinase, responsible for the processing of nonstructural polypeptides, and a C-terminal nucleoside triphosphatase/helicase, presumably involved in the unwinding of the viral genome. The human antibody response to NS3 usually appears early in the course of HCV infection and is predominantly directed against the carboxyl-terminal portion; however, its fine specificity and clinical significance are largely unknown. We have generated a human monoclonal antibody (hMAb), designated CM3.B6, from a cloned B-cell line obtained from the peripheral blood of a patient with chronic HCV infection, which selectively recognized the purified NS3 protein expressed in bacteria or in eukaryotic cells transfected with full-length or NS3 cDNA. Fine-specificity studies revealed that CM3.B6 recognized a 92-amino-acid sequence (clone 8, amino acids 1363 to 1454) selected from an NS3 DNase fragment library but failed to bind to 12-mer peptides synthesized from the same region, suggesting recognition of a conformational B-cell epitope. Experiments using deletion mutants of clone 8 and competitive inhibition studies using a panel of NS3 peptide-specific murine MAbs indicated that limited N-terminal and C-terminal deletions resulted in a significant reduction of hMAb binding to clone 8, thus identifying a minimal antibody binding domain within clone 8. Competition experiments showed that binding of CM3.B6 to the NS3 protein was efficiently inhibited by 39 of 44 (89%) sera from HCV-infected patients, suggesting that the hMAb recognized an immunodominant epitope within the NS3 region. More importantly, recognition of the sequence defined by CM3.B6 appeared to accurately discriminate between viremic and nonviremic anti-HCV positive sera, suggesting potentially relevant clinical applications in the diagnosis and treatment of HCV infection.
Near infrared monitoring of human skeletal muscle oxygenation during forearm ischemia (1988)

Changes in tissue oxygenation of forearm muscles were measured by near infrared (NIR) spectrophotometry in 10 healthy adults during tourniquet ischemia and venous outflow restriction. Muscle O2 stores were depleted rapidly by forearm ischemia manifest by a progressive decrease in tissue oxyhemoglobin and oxymyoglobin over 4-5 min. Muscle ischemia significantly decreased the oxidation level of cytochrome aa3, to below resting base line after only 1.5 min, and the enzyme became fully reduced after 6.5 min. After 8 min of ischemia, tourniquet release was accompanied by a transient increase in muscle blood volume due to influx of oxyhemoglobin. The cytochrome aa3 oxidation level increased above resting base line within 1 min after tourniquet release. Transcutaneous PO2 measurements recorded simultaneously from the same forearm correlated poorly with the kinetics of O2 availability and cytochrome oxidation in the underlying muscle tissue; this was not unexpected because overlying skin did not contribute significantly to NIR muscle signals. Venous outflow restriction without inflow obstruction increased muscle deoxyhemoglobin and tissue blood volume but did not change muscle O2 stores or cytochrome aa3 oxidation level. The ability of the NIR technique to detect dynamic trends in tissue oxygenation reveals that muscle O2 is rapidly consumed during tourniquet ischemia and rapidly restored by hyperemic responses after brief ischemia.
Development of an in vivo glucosylation platform by coupling production to growth: Production of phenolic glucosides by a glycosyltransferase of Vitis vinifera (2015)

Glycosylation of small molecules can significantly alter their properties such as solubility, stability, and/or bioactivity, making glycosides attractive and highly demanded compounds. Consequently, many biotechnological glycosylation approaches have been developed, with enzymatic synthesis and whole-cell biocatalysis as the most prominent techniques. However, most processes still suffer from low yields, production rates and inefficient UDP-sugar formation. To this end, a novel metabolic engineering strategy is presented for the in vivo glucosylation of small molecules in Escherichia coli W. This strategy focuses on the introduction of an alternative sucrose metabolism using sucrose phosphorylase for the direct and efficient generation of glucose 1-phosphate as precursor for UDP-glucose formation and fructose, which serves as a carbon source for growth. By targeted gene deletions, a split metabolism is created whereby glucose 1-phosphate is rerouted from the glycolysis to product formation (i.e., glucosylation). Further, the production pathway was enhanced by increasing and preserving the intracellular UDP-glucose pool. Expression of a versatile glucosyltransferase from Vitis vinifera (VvGT2) enabled the strain to efficiently produce 14 glucose esters of various hydroxycinnamates and hydroxybenzoates with conversion yields up to 100%. To our knowledge, this fast growing (and simultaneously producing) E. coli mutant is the first versatile host described for the glucosylation of phenolic acids in a fermentative way using only sucrose as a cheap and sustainable carbon source.
Synthesis and Biological Activities of Optically Active 6-(3-(3,4-Dimethoxybenzylamino)-2-hydroxypropoxy)-2(1H)-quinolinone (OPC-18790). (1996)

The enantiomers of 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinon e (OPC-18790), a novel cardiotonic agent, were synthesized and evaluated for positive inotropic activity. The key intermediates, 2,3-epoxypropoxy derivatives, were obtained by the alkylation of 6-hydroxy-2(1H)-quinolinone with optically active epichlorohydrin and subsequent ring closure. In an in vitro study, the (R)-(+)-isomer was about 10-fold more potent than the (S)-(-)-isomer.
EXCESS MORTALITY FROM EPIDEMIC INFLUENZA, 1957–1966 (1974)

Housworth, J. (Bureau of Epidemiology. Center for Disease Control, Atlanta. Georgia 30333) and A. D. Langmuir. Excess mortality from epidemic influenza. 1957–1966. Am J Epidemiol 100: 40–48. 1974.—A study of excess mortality in the United States from 1957 through 1966 revealed seven epidemic periods associated with the prevalence of influenza A2 or B or both infections, and one period in July 1966 associated with a heat wave. More than half of the excess deaths are attributed to diseases of the heart, or the circulatory or nervous systems. The proportion ascribed to respiratory causes varies from 38% in severe epidemics of influenza A2 to as low as 22% during mild epidemics of influenza B. Severe epidemics of influenza result in small but significant excess mortality attributed to tuberculosis, asthma, chronic rheumatic heart disease, diabetes, and neoplasms. Maternal deaths showed no excess mortality during influenza epidemics. Similarly, infant mortality was not influenced to a measurable degree by influenza epidemics.
The Xenopus T-box gene, Antipodean, encodes a vegetally localised maternal mRNA and can trigger mesoderm formation (1996)

We have used differential display to identify genes inducible by activin and isolated a novel member of the T-box gene family that includes the Xenopus genes Xbrachyury and Eomesodermin. Here we show that this novel gene is unique within the T-box family because it is maternally expressed at a high level. Furthermore, it belongs to a rare class of maternal mRNAs in Xenopus that are localised to the vegetal hemisphere of the egg and we have therefore named it Antipodean. We show here that low amounts of Antipodean injected into ectoderm (animal cap cells) strongly induce pan mesodermal genes such as Xbrachyury and ventral mesodermal genes such as Xwnt-8. Overexpression of Antipodean generates mesoderm of ventral character, and induces muscle only weakly. This property is consistent with the observed late zygotic Antipodean mRNA expression in the posterior paraxial mesoderm and ventral blastopore, and its exclusion from the most dorsal mesodermal structure, the notochord. Antipodean is induced by several molecules of the TGF-beta class, but in contrast to Xbrachyury, not by bFGF. This result suggests that the expression of these T-box genes may be under the control of different regulatory pathways. Finally, we demonstrate that Antipodean and Eomesodermin induce each other and both are able to induce Xbrachyury. The early zygotic expression of Antipodean is not induced by Xbrachyury, though later it is to some extent. Considering its maternal content, Antipodean could initiate a cascade of T-box gene activations. The expression of these genes may, in turn, sustain each other's expression to define and maintain the mesoderm identity in Xenopus.
The National Ignition Facility Project (1994)

The mission of the National Ignition Facility is to achieve ignition and gain in inertial confinement fusion targets in the laboratory. The facility will be used for defense applications such as weapons physics and weapons effects testing, and for civilian applications such as fusion energy development and fundamental studies of matter at high temperatures and densities. This paper reviews the design, schedule, and costs associated with the construction project.
Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. (1985)

The drug 5-azacytidine was injected into mice to activate silent retroviral genomes. The Mov-7 and Mov-10 substrains of mice were used, each of which carries a Moloney murine leukemia provirus with mutations in the coding regions at nonidentical positions. These proviral genomes are highly methylated and are not expressed in the animal. A single injection of the drug into postnatal mice induced transcription of the endogenous defective proviral genomes in thymus, spleen, and liver at 3 days after treatment. No viral transcription was detected in the brain of drug-exposed animals. When postnatal Mov-7/Mov-10 F1 mice were treated with the drug, infectious virus was generated efficiently and resulted in virus spread and viremia in all animals by 3 weeks of age. In contrast, infectious virus was not generated in F1 mice that had been treated during gestation with up to sublethal doses of the drug. Our results demonstrate that injection of 5-azacytidine can be used to efficiently and reproducibly activate silent genes in different cell populations of postnatal mice.
<title>Holographic Optical Interconnects For VLSI</title> (1986)

This paper introduces new applications and design trade-offs anticipated for free-space optical interconnections of VLSI chips. New implementations of VLSI functions are described that use the capability of making optical inputs at any point on a chip and take advantage of greater flexibility in on-chip signal routing. These include n-port addressable memories, CPU clock phase distribution, hardware multipliers, and dynamic memory refresh, as well as enhanced testability. Fault tolerance and production yields may be improved by reprogramming the optical imaging system to circumvent defective elements. These attributes, as well as those related to performance alone, will affect the design methodology of future VLSI ICs. This paper focuses on identifying the design issues, their possible solutions, and their impact on VLSI design tech-niques and, finally, presents some preliminary measurements on various sys-tem components.
Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus (1987)

A recombinant vaccinia virus containing cloned DNA sequences coding for the three structural proteins and nonstructural proteins NS1 and NS2a of dengue type 4 virus was constructed. Infection of CV-1 cells with this recombinant virus produced dengue virus structural proteins as well as the nonstructural protein NS1. These proteins were precipitated by specific antisera and exhibited the same molecular size and glycosylation patterns as authentic dengue virus proteins. Infection of cotton rats with the recombinant virus induced NS1 antibodies in 1 of 11 animals. However, an immune response to the PreM and E glycoproteins was not detected. A reduced level of gene expression was probably the reason for the limited serologic response to these dengue virus antigens.
Effects of iron depletion and sab-inhibitory concentrations of antibiotics on siderophore production by Staphylococcus aureus (1991)

The effect of various sub-MICs of oxacillin and amikacin, alone or in combination, on siderophore production by Staphylococcus aureus growing under iron-depleted conditions was evaluated. Siderophore production varied greatly from strain to strain, ranging from 3.0 to 383.4 microM of Desferal equivalents. Siderophore production by some S. aureus strains was reduced significantly (P less than 0.001) under some sets of conditions. However, siderophore excretion in cultures with amikacin was sometimes equal to or greater than control cultures. Thus, at some sub-MICs, the bacteria tested were able to increase siderophore production under metabolic stress. This phenomenon may be a secondary effect of the antibiotics upon intermediary metabolism as a consequence of inhibition of peptidoglycan or protein synthesis. Alternatively the antibiotics may decrease the cellular association of siderophore molecules.
A Chemical Proteomics Approach for the Identification of Accessible Antigens Expressed in Human Kidney Cancer (2006)

A promising avenue toward the development of more selective anticancer drugs consists in the targeted delivery of bioactive molecules to the tumor environment by means of binding molecules specific to tumor-associated markers. We have used a chemical proteomics approach based on the ex vivo perfusion and biotinylation of accessible structures within surgically resected human kidneys with tumor to gain information about accessible and abundant antigens that are overexpressed in human cancer. This procedure led to the selective labeling with biotin of vascular structures. Biotinylated proteins were purified on streptavidin resin and identified using mass spectrometric methodologies, revealing 637 proteins, 184 of which were only found in tumor specimens and 223 of which were only found in portions of normal kidneys. Immunohistochemical and PCR analysis confirmed that several of the putative cancer antigens identified in this study are indeed preferentially expressed in tumors. In conclusion, we have developed a methodology that allows the identification of accessible biomarkers in human tissues. The tumor-associated antigens identified in this study may be suitable targets for antibody-based anticancer therapies. The experimental approach described here should be applicable to other surgical specimens and to other pathologies as well as to the study of basic physiological and immunological processes.
Cannabidiol: An Overview of Some Pharmacological Aspects (2002)

Over the past few years, considerable attention has focused on cannabidiol (CBD), a major nonpsychotropic constituent of cannabis. The authors present a review on the chemistry of CBD and discuss the anticonvulsive, antianxiety, antipsychotic, antinausea, and antirheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors, and its mechanism of action is yet unknown. It is possible that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its antioxidative effect.
Fossil Fuels (1996)

The sections in this article are 1 Introduction 2 Applications to Coal Science 3 Applications to Shale Oil Research 4 Other Fuels 5 Biographical Sketch Related Articles
Leukocytes drop anchor (2012)

![Figure][1] 

To avoid being displaced by fluid flow, monocytes accumulate F-actin (green) in upstream structures (arrowheads), which keep the cells firmly anchored to their attachment site.



Rullo et al. describe how actin polymerization helps leukocytes maintain their attachments to blood
Expression and subcellular locations of two forms of nucleolar protein B23 in rat tissues and cells. (1993)

Protein B23 (Mr/pI = 38,000/5.1) is a major RNA-associated nucleolar phosphoprotein and putative ribosome assembly factor. Previous cDNA and genomic analyses indicated the presence of two forms of the protein (B23.1 and B23.2) which arise from a single gene via alternative splicing. Expression of the two B23 isoforms in rat tissues cells has been studied at the mRNA level using northern blot and RNA-polymerase chain reaction analyses and at the protein level by western blotting. In all tissues examined, the relative amount of B23.1 mRNA was much higher (3-6-fold) than B23.2 mRNA. For B23.1, the level of mRNA and protein expression was highest in Novikoff hepatoma cells, followed by testis, liver, and kidney. This suggests that B23.1 expression is correlated with the rate of proliferation of the tissue and/or the rate of ribosome biogenesis. In contrast, the amount of B23.2 mRNA did not vary significantly among the three normal tissues, although it was elevated in Novikoff hepatoma cells. Similarly, the B23.2 protein was barely detectable in the normal rat tissues, but significant quantities were found in the Novikoff cells. In cell fractionation experiments, B23.1 was predominantly found in nucleoli, whereas B23.2 was located in cytoplasmic fractions and appeared to be associated with cytoskeletal elements. These studies suggest that the two protein B23 isoforms are engaged in very different functions.
Effect of Jiajianxiayuxuetang on Mice Podocyte Secretion of Vascular Endothelial Growth Factor (2007)

Objective:To investegate the effect of jiajianxiayuxuetang on cultured mice podocyte secretion of vascular endothelial growth factor(VEGF)induced by lipid in vitro.Methods:RT-PCR and ELISA method were applied to investigate the influence of low-density-liportein (LDL) and oxident-LDL(OX-LDL)of different concentrations on the podocyte secretion of VEGF, and the effect of serum contained jiajianxiayuexuetang of different concentrations.Results:LDL and OX-LDL could increase podocyte secretion of VEGF in a dosage-dependent manner, and the serum contained jiajianxiayuexuetang could significantly inhibit the over-expression of VEGF induced by lipid.Conclusion:LDL and OX-LDL might cause severe lipid nephrotoxicity by increasing the podocyte secretion of VEGF. Chinese herb Jiajianyuxuetang may protect the podocyte from lipid nephrotoxicity via reducing the over-secretion of VEGF induced by lipid.
Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins (1980)

Cells nonproductively transformed by the Snyder-Theilen, Gardner-Arnstein, and McDonough strains of feline sarcoma virus synthesize gag-x polyproteins of 78,000, 100,000, and 180,000 daltons, respectively. These feline sarcoma virus-coded products were precipitated by antisera to polypeptides encoded by the gag gene of feline leukemia virus and by rat antisera raised to feline sarcoma virus-transformed rat tumor cells. Precipitation with rat antisera absorbed with feline leukemia virus showed that the x-portions of the three gag-x proteins were each antigenically distinct, suggesting that the src genes of the three independent isolates are not identical. Anti-x sera did not precipitate products from radiolabeled cat lymphoid tumor cells (FL74) and therefore lacked reactivity to the feline leukemia virus-induced tumor-specific antigen, FOCMA.
436. Recombinant Adeno-Associated Virus Gene Therapy for Cob(I)Alamin Adenosyltransferase Deficiency (2004)

Metabolism of inactive cobalamins, both in the recycling and assimilation from dietary sources, into the B12 coenzymes is vital for various metabolic pathways. Disruption of vitamin B12 coenzyme synthesis has been linked to chronic liver disease, cancer, elevated serum homocysteine (possible risk factor for heart disease), increased rate of DNA damage and impaired cognitive function. Vitamin B12 (cyano-cobalamin, CNCbl) is a precursor of two B12 coenzymes, adenosyl-cobalamin (AdoCbl) and methyl-cobalamin (CH3Cbl), which are instable due to a labile upper ligand to the cobalt atom. The assimilation and recycling pathway consists of a multi-enzyme pathway, the last step being the conversion of cob(I)alamin to AdoCbl by the ATP dependent cob(I)alamin adenosyltransferase (ATR). In humans, methylmalonyl-CoA mutase (MCM), responsible for the conversion of propionyl-CoA to the TCA cycle intermediate succinyl-CoA, is dependent on AdoCbl. Propionyl-CoA is produced by the catabolism of the amino acids valine, isoleucine, methionine, and threonine, as well as thymine, cholesterol and odd-chain fatty acids. The impaired activity of MCM, resulting from the lack of coenzyme B12 (AdoCbl), leads to methylmalonic aciduria (MMA), a disease that is often fatal in the first years of life with a frequency of 1/50,000 births. MMA is diagnosed primarily by a buildup of methylmalonyl-CoA in the serum and in the urine. We have obtained human fibroblast cell lines from patients with known ATR deficiencies. Identification of mutations, generally seen to be a single nucleotide or missense mutation, have been performed on most. The human ATR cDNA is 753 bp, the appropriate length for use in rAAV gene therapy vector. It has been cloned into our rAAV vector driving expression of hATR from the hybrid CMV enhancer chicken-beta actin promoter and pseudotyped in AAV 2 and 8 capsids. Next, cell lines were stably transfected with an ATR-neo plasmid and selected for using G418. Levels of methylmalonic acid in the tissue culture medium is measured using tandem mass spectroscopy and an enzyme assay for the conversion of cob(I)alamin to AdoCbl with the ATR enzyme. RESULTS: Overexpression of hATR message from the pCB-hATR vector in patient and control cell lines was confirmed by semi-quantitative RT-PCR. Transgene expression in neomycin resistant clones was 3 to 7 times greater than endogenous expression. Correction of deficient patient cell lines will be assayed at varying doses of rAAV virus. Further experiments will include testing vector expressed ATR mRNA and increased enzyme acitivity in the muscle and liver tissues of C57Bl/6 mice.