gebhart/patrepeval huggingface dataset:
Inhibition of Neisseria gonorrhoeae by aerobic and facultatively anaerobic components of the endocervical flora: evidence for a protective effect against infection (1978)

The ability of aerobic and facultatively anaerobic endocervical flora to inhibit the growth of Neisseria gonorrhoeae in vitro was assayed. Factors influencing the occurrence of inhibitory components of the flora in vivo were evaluated. Endocervical swabs were obtained from 229 women at a local venereal disease clinic. Endocervical flora and N. gonorrhoeae were isolated and identified, and the ability of the flora to inhibit the growth of N. gonorrhoeae was determined by an agar overlay assay. Results revealed the most active inhibitors to be streptococci, staphylococci, and lactobacilli, in that order. Among only those women harboring inhibitory endocervical flora, inhibitory lactobacilli were recovered from fewer women infected with N. gonorrhoeae than uninfected women (P less than 0.05). Among women having contact with an infected partner, those who subsequently developed gonorrhea were less likely to have inhibitory lactobacilli than those who did not become infected (P less than 0.05). No other significant differences in the composition of the inhibitory flora were noted between infected and uninfected women. During the 2 weeks following menses, recovery of inhibitory lactobacilli on culture was highest, whereas recovery of N. gonorrhoeae was lowest. These observations suggest that the presence of certain lactobacilli may reduce risk of acquisition of N. gonorrhoeae following exposure to infected partners and that the potential protective effect may be greatest during the 2 weeks after menses.
In vivo activity of tumor necrosis factor (TNF) mutants. Secretory but not membrane-bound TNF mediates the regression of retrovirally transduced murine tumor (1992)

We have previously demonstrated that murine tumor cells transduced with a retrovirus containing the cDNA encoding wild-type human TNF regress in vivo when injected into immunocompetent mice; this regression is T cell mediated. To determine whether membrane-associated or secreted TNF was responsible for tumor regression, we transduced a cloned murine fibrosarcoma 205 F4 with retroviruses encoding modified human TNF genes. The cloned tumor lines of one retroviral transduction expressed only membrane bound 26-kDa TNF. This TNF could not be cleaved or secreted, but was present on the cell surface. A second retrovirus caused the expression of only secretory 17-kDa TNF, as the transmembrane domain of the cDNA was deleted. The TNF produced by tumor cells transduced with either retroviral vector was functional in vitro as direct lysis of the TNF-sensitive target L929 by transduced tumor cells was demonstrated. The TNF present on 26-kDa expressing tumors was membrane bound as supernatants from cultured 17-kDa TNF expressing tumor cells but not 26-kDa TNF expressing tumors mediated the lysis of L929 cells. Both tumors were injected s.c. into syngeneic mice and tumor growth was measured serially. In repeated experiments, 26-kDa TNF expressing tumors grew progressively in all mice. In contrast, 17-kDa TNF expressing tumors grew for 10 days and then regressed with all animals free of tumor at 28 days. Tumor regression was abrogated by in vivo injection of an anti-TNF antibody. Similar results were obtained in a second tumor model, 203 E4. Thus regression of TNF transduced tumors in vivo requires secretion of TNF, as membrane-bound TNF is insufficient to elicit the host response.
Insulin-Dependent Diabetes in the Nod Mouse Model II. β Cell Destruction in Autoimmune Diabetes is a TH2and not A TH1Mediated Event (1993)

Type I, insulin-dependent diabetes (IDD) in both man and animals results from a specific autoimmune destruction of the pancreatic beta cells involving both humoral and cellular immune mechanisms. The pathognomonic histologic lesion, termed insulitis, is an inflammatory and immune cell infiltrate of the pancreatic islet cells. While recent histological and flow cytometric analyses have identified the cell composition of the infiltrate, the presence of a cell population may not reflect the functional reactivities important for beta cell destruction. In the present study, we have investigated the possible functional reactivities of islet-infiltrating mononuclear cell populations by measuring increased cytokine mRNA usage. Results indicate that 1) cytokine mRNA profiles exhibited by islet-infiltrating cells of female and male NOD mice were quite similar with the exception of IL-6 expression and the marked differences in the levels of IL-2 receptor and IL-1 alpha mRNA, 2) CD4+ T lymphocytes expressed IL-4, presumably IL-5, and occasionally IL-10 mRNA but no detectable IL-2 mRNA, 3) CD8+ T lymphocytes exhibited TNF-beta, perforin and high levels of IFN-gamma, and 4) IL-7 was expressed in the islet at very high levels. These findings, together with our earlier flow cytometric analyses of the islet-infiltrating cells, have permitted construction of a detailed model for the natural history of autoimmune diabetes. Interestingly, this model, based on a TH2- and not a TH1-mediated scheme, questions the more popular concepts currently thought to form the bases of the autoimmune reactions underlying IDD.
The UCSC Genome Browser database: update 2011 (2010)

The University of California, Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online access to a database of genomic sequence and annotation data for a wide variety of organisms. The Browser also has many tools for visualizing, comparing and analyzing both publicly available and user-generated genomic data sets, aligning sequences and uploading user data. Among the features released this year are a gene search tool and annotation track drag-reorder functionality as well as support for BAM and BigWig/BigBed file formats. New display enhancements include overlay of multiple wiggle tracks through use of transparent coloring, options for displaying transformed wiggle data, a 'mean+whiskers' windowing function for display of wiggle data at high zoom levels, and more color schemes for microarray data. New data highlights include seven new genome assemblies, a Neandertal genome data portal, phenotype and disease association data, a human RNA editing track, and a zebrafish Conservation track. We also describe updates to existing tracks.
Anti-erythropoietin (EPO) receptor monoclonal antibodies distinguish EPO-dependent and EPO-independent erythroid progenitors in polycythemia vera (1994)

Erythroid progenitor cells isolated from patients with polycythemia vera (PV) proliferate and differentiate in methylcellulose in the absence of exogenous erythropoietin (EPO). To investigate the potential role of the erythropoietin receptor (EPO-R) in the pathogenesis of PV, we cultured bone marrow-derived or peripheral blood-derived erythroid progenitors in the presence of neutralizing monoclonal antibodies (MoAbs) specific for EPO or EPO-R. Mononuclear cells were obtained from 9 healthy adults and 9 PV patients by Ficoll-Hypaque gradients and cultured with or without EPO in methylcellulose for 12 days under standard or serum-free conditions. Neutralizing anti-EPO and anti-EPO-R MoAbs, added to cultures at day 0, caused dose-dependent growth inhibition of all normal burst-forming units-erythroid (BFU-E) derived from health adult controls. The MoAbs had no effect on the growth of nonerythroid progenitor cells under the same culture conditions. In contrast, neutralizing antibodies distinguished two classes of BFU-E derived from PV patients. Class I BFU-E from PV patients were EPO- dependent. These progenitors, like those derived from healthy adults, had normal EPO dose-dependent growth characteristics and showed a normal period of EPO requirement in vitro that extended 6 days after the initiation of culture. These results indicate that EPO exerts its critical effect early during erythroid differentiation; the addition of neutralizing antibodies to normal progenitors after 6 days had no effect on the subsequent size or maturation of the colonies. Class II BFU-E from PV patients were EPO-independent. They proliferated and differentiated even in the presence of high concentrations of neutralizing anti-EPO or anti-EPO-R MoAbs. We conclude that the class II BFU-E from PV patients are independent of free EPO.
High-Spatial Resolution Mass Spectrometric Imaging of Peptide and Protein Distributions on a Surface (2004)

For the first time macromolecular ion microscope images have been recorded using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Single-shot, mass-resolved images of the spatial distributions of intact peptide and protein ions over an area of 200 microm in diameter were obtained in less than 1 ms at a repetition rate of 12 Hz. The magnifying ion optics of the ion microscope allowed ion images to be obtained with a lateral resolution of 4 microm. These results prove the concept of high-resolution MALDI-MS imaging in microscope mode without the need for a tight laser focus and the accompanying sensitivity losses. The ion microscopy approach offers an improvement of several orders of magnitude in speed of acquisition compared to the conventional (microprobe) approach to MALDI-MS imaging.
Chemokine Receptor CCR3 Function Is Highly Dependent on Local pH and Ionic Strength (1997)

The CC chemokine receptor 3 (CCR3) plays an important role in the regulation of the migration of eosinophils, a leukocyte population involved in many inflammatory pathologies including asthma. CCR3 binds to the CC chemokine eotaxin, a promigratory cytokine originally isolated as the key component in a model of eosinophil-induced airway inflammation. We show here that eotaxin/CCR3 binding interactions exhibit a marked sensitivity to relatively small changes in the extracellular environment. In particular, modest variations in the pH and the level of sodium chloride over a range of physiologic and near physiologic conditions had dramatic effects on eotaxin binding and CCR3-mediated cytoplasmic Ca2+ mobilization. These biochemical indices were reflected at the functional level as well; small changes in pH and salt also resulted in striking changes in the migration of primary human eosinophils in vitro. These results reveal that relatively small perturbations in extracellular buffer conditions can yield widely disparate interpretations of CCR3 ligand binding and affinities and suggest that modulation of the tissue microenvironment might be utilized to control the affinity and efficacy of chemokine-mediated cell migration.
RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. (1985)

Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I and II). Cytological hybridization with metaphase chromosomes indicated that both genes reside on rat chromosome I but are approximately 100,000 kilobases apart. In mice the two genes reside on two different chromosomes. DNA sequence comparisons of the gene-flanking regions in rats and mice indicated that the preproinsulin gene I has lost one of the two introns present in gene II, is flanked by a long (41-base) direct repeat, and has a remnant of a polydeoxyadenylate acid tract preceding the downstream direct repeat. These structural features indicated that gene I was generated by an RNA-mediated duplication-transposition event involving a transcript of gene II which was initiated upstream from the normal capping site. Sequence divergence analysis indicated that the pair of the original gene and its retroposed, but functional, counterpart (which appeared about 35 million years ago) is maintained by strong negative selection operating primarily on the segments encoding the chains of the mature hormone, whereas the segments encoding the parts of the polypeptide that are eliminated during processing and also the introns and the flanking regions are evolving neutrally.
The Ecoresponsive Genome of Daphnia pulex (2011)

We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.
Tazarotene-Induced Gene 1 (TIG1) Expression in Prostate Carcinomas and Its Relationship to Tumorigenicity (2002)

TIG1 may be a tumor suppressor gene whose diminished expression is involved in the malignant progression of prostate cancer.
A study of an electronic nose for detection of lung cancer based on a virtual SAW gas sensors array and imaging recognition method (2005)

In this paper, we propose an electronic nose for non-invasive detection and diagnosis of lung cancer based on a kind of virtual array of surface acoustic wave (SAW) gas sensors and an imaging recognition method. It includes a gas path constructed from a two-bag system, solid phase micro extraction (SPME) and a capillary column to pre-concentrate and separate volatile organic compounds (VOCs) in patients' exhaled air. A pair of SAW sensors, one coated with a thin polyisobutylene (PIB) film, is used to detect chemical compounds. Eleven VOCs that are validated as the markers of lung cancer according to a pathology study can be detected qualitatively and quantitatively by this electronic nose. Then, an improved artificial neural network (ANN) algorithm combined with an imaging method is proposed for the recognition of patients. In addition, the concept of a virtual sensors array based on SAW sensors using a capillary column separation technique and imaging is also proposed to simulate a large scale of sensor array response. Finally this e-nose is calibrated by these 11 VOCs separated in three concentrations and is used to diagnose lung cancer patients in Run Run Shaw hospital. The experimental results show that this kind of electronic nose is effective in the recognition of lung cancer patients.
counterfeiters dye over security measures (2001)

Photo-luminescent dyes are emerging as an important tool in this struggle. Novel dye materials with unique properties are read by special scanners and allow authorities to detect, track, and study the counterfeit trade
Bovine papilloma virus-transformed cells contain multiple E2 proteins. (1988)

Genetic evidence suggests that the bovine papilloma virus type 1 (BPV) E2 open reading frame may encode at least two gene products involved in the regulation of viral gene expression. One, which is probably the full-length product, trans-activates transcription via an enhancer in the viral regulatory region. A second, containing sequences from the 3' end of the open reading frame, inhibits the trans-activating activity of the first product. We now report the identification and initial characterization of three E2-encoded proteins, with mobilities corresponding to 48, 31, and 28 kDa in cells transformed by the wild-type BPV. Pulse-chase experiments indicated that the 48-kDa protein had the longest half-life (40 min), but there was no indication that one species was the precursor of another. The 48-kDa species corresponds to the full-length trans-activating protein. The two smaller species contain only carboxyl-terminal determinants, and either or both could represent inhibitory E2 proteins. Subcellular fractionation localized all three E2 proteins to the nucleus. Consistent with the low rate of viral transcription in BPV-transformed cells, the 31-kDa presumptive repressor species was more abundant than the 48-kDa species.
Efficient production of human bivalent and trivalent anti-MUC1 Fab-scFv antibodies in Pichia pastoris (2009)

Bi- and tribody molecules are efficiently produced in P. pastoris. Furthermore, the yeast produced molecules retain the same specific affinity for their antigen. These results establish the value of P. pastoris as an efficient alternative expression system for the production of recombinant multivalent Fab-scFv antibody derivatives.
Repetitive Proteins And Genes Of Malaria (1987)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Deamidation via cyclic imide of asparaginyl peptides: dependence on salts, buffers and organic solvents. (1992)

The deamidation reaction of Asn side chain was studied in the presence of the chemicals usually used at high concentration in the purification and crystallization of peptides and proteins. All the experiments were performed on the model peptide Boc-L-Asn-Gly-Gly-NH2. The pathway of the reaction is not affected by the medium used; in all cases it proceeds through a succinimide intermediate giving a mixture of isoaspartyl and aspartyl peptide. However, the rate of the reaction significantly depends on the solvent: the addition of organic solvents to an aqueous solution of the peptide has the general effect of decreasing the reaction rate, which, on the other hand, is strongly enhanced by a high concentration of organic and inorganic buffers. Only a minor influence is exerted by aprotic salts and polyethylene glycol.
Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines (1982)

We studied the effects of nerve growth factor (NGF) to determine whether neuroblastoma (NB) cells share the pattern of altered response to growth regulatory factors shown by various malignant transformed cells. NGF induces neurite outgrowth, arrests growth, and enhances survival in normal neurons and in the rat pheochromocytoma, a tumor cell closely related to NB. With respect to neurite outgrowth, lines SK-N-SH, SH-SY5Y, LA-N-5, and CHP-126 were sensitive, IMR-32 was resistant, and SH-EP1, SK-N-MC, MC-IXC, CHP-100, and CHP-134 were unresponsive. Conditioned media from unresponsive cells did not inhibit response in sensitive cells. Unexpectedly, NGF neither reduced the growth rate nor enhanced survival in any NB cell line. Conditioned medium from all NB cell lines enhanced 125I-NGF binding in embryonic sensory cells. Regulation of growth rate and neurite outgrowth, then, are separable. A fundamental defect in NB may be the acquisition of a capacity for growth and survival independent of NGF. 125I-NGF was bound to both Fast and Slow receptors in MC-IXC cells, but only to Slow receptors in NGF-responsive SH-SY5Y and LA-N-5 cells, showing Fast receptors are not required for neurite outgrowth. Independence from NGF-regulated growth and survival is unexplainable by an absence of NGF receptors.
Pharmacokinetics and Tolerability of Daptomycin at Doses up to 12 Milligrams per Kilogram of Body Weight Once Daily in Healthy Volunteers (2006)

Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.
Overproduction of Bacterial Protein Disulfide Isomerase (DsbC) and Its Modulator (DsbD) Markedly Enhances Periplasmic Production of Human Nerve Growth Factor in Escherichia coli (2001)

Production of eukaryotic proteins with multiple disulfide bonds in the Escherichia coli periplasm often encounters difficulty in obtaining soluble products with native structure. Human nerve growth factor beta (NGF) contains three disulfide bonds between nonconsecutive cysteine residues and forms insoluble aggregates when expressed in E. coli. We now report that overexpression of Dsb proteins known to catalyze formation and isomerization of disulfide bonds can substantially enhance periplasmic production of NGF. A set of pACYC184-based plasmids that permit dsb expression under the araB promoter were introduced into cells carrying a compatible plasmid that expresses NGF. The efficiency of periplasmic production of NGF fused to the OmpT signal peptide was strikingly improved by coexpression of DsbCD or DsbABCD proteins (up to 80% of total NGF produced). Coexpression of DsbAB was hardly effective, whereas that of DsbAC increased the total yield but not the periplasmic expression. These results suggest synergistic roles of DsbC and DsbD in disulfide isomerization that appear to become limiting upon NGF production. Furthermore, recombinant NGF produced with excess DsbCD (or DsbABCD) was biologically active judged by the neurite outgrowth assay using rat PC12 cells.
Studies in the friedel-crafts reaction: Part VI-Synthesis and intra-, and intermolecular friedel-crafts reaction of 2-methyl-4-phenylpentanedioic anhydride (2002)

2-Methyl-4-phenylpentanedioic acid 4 is prepared by the Michael reaction of methyl methacrylate with ethyl/methyl phenylacetate or benzyl cyanide followed by the hydrolysis of the adduct. The reaction has been studied using different bases. 4 is converted to its anhydride 5, which on intermolecular Friedel-crafts reaction with AlCl 3 gives 2-methyl-1-tetralone-4-carboxylic acid while its reaction with aryl ethers in the presence of AlCl 3 gives a series of 5-aryl-4-methyl-5-oxo-2-phenylpentanoic acid 8.
Results from a Phase IIb, Randomized, Multicenter Study of GVAX Pancreas and CRS-207 Compared with Chemotherapy in Adults with Previously Treated Metastatic Pancreatic Adenocarcinoma (ECLIPSE Study) (2019)

The combination of Cy/GVAX + CRS-207 did not improve survival over chemotherapy. (ClinicalTrials.gov ID: NCT02004262)<i>See related commentary by Salas-Benito et al., p. 5435</i>.