gebhart/patrepeval huggingface dataset:
Correlation of modified human papilloma virus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. (1988)

In cervical carcinomas and cell lines derived from these tumors the DNA of specific types of human papilloma viruses (HPVs) is integrated into the host cell genome. The two viral open reading frames E6 and E7 are consistently transcribed in tumors and cell lines, and the respective proteins were detected in cells cultured in vitro. As shown here, modulation of HPV 18 E6 and E7 gene expression in C4-1 cervical carcinoma cells is accompanied by an altered cell growth. HPV 18 E6 and E7 expression can be enhanced by glucocorticoid treatment of C4-1 cells, and an increased cell proliferation is observed. In contrast, after introduction of complementary RNA to the HPV 18 E6 and E7 open reading frames, their expression is inhibited, and decreased cell growth is observed. These results support the hypothesis that expression of HPV E6 and E7 open reading frames is directly involved in growth regulation of cervical carcinoma cells.
Neurosecretory control of aging in Caenorhabditis elegans (1999)

In the nematode Caenorhabditis elegans, an insulin receptor signaling pathway regulates adult life span and developmental arrest at the dauer larval stage. Here we show that the unc-64 and unc-31 genes also function in this pathway. These two genes are involved in mediating Ca2+-regulated secretion. Mutations in unc-64 and unc-31 increase adult life span and cause constitutive dauer formation. Both phenotypes are suppressed by mutations in daf-16, which also suppresses other mutations in this pathway. We present evidence that the site of action of unc-64 is neuronal, suggesting that a neurosecretory signal regulates life span and dauer formation.
The role of Haemagglutinin-Neuraminidase Glycoprotein Cell Surface Expression in the Survival of Sendai Virus-infected BHK-21 Cells (1985)

SUMMARY A temperature-sensitive mutant of Sendai virus with a lesion in the haemagglutinin-neuraminidase protein (HN) (ts 271) was used to study the effect of HN cell surface expression on the fate of infected BHK-21 cells. The total amount of HN was reduced in ts 271 virus-infected cells at the non-permissive temperature (38 °C) presumably due to degradation of the protein. At this temperature, neither HN nor a modified form of HN were found expressed at the surface of the infected cells. BHK-21 cells infected with ts 271 were nevertheless killed by the infection at 38 °C as well as at 30 °C. These results ruled out the hypothesis that the lack of HN cell surface expression could be the unique requirement allowing BHK cell survival.
Different Metabolism of Hexose Sugars and Sucrose in Wound Fluid and in Fibroblast Cultures Derived from Granulation Tissue, Hypertrophic Scar and Keloid (2000)

Viscose cellulose sponge implants in the rat and fibroblast cultures established from granulation tissue, hypertrophic scar, or keloid were treated with different concentrations of glucose, fructose, galactose, mannose, and sucrose. The concentrations of the above-mentioned sugars in wound fluid and cell culture medium were examined at the termination of experiments by liquid chromatography. Results showed that glucose was present in wound fluid in relatively low levels. In addition to glucose, only mannose was found in wound fluid. On the other hand, cell culture studies showed that virtually all the added sugars were found in cell culture medium. The most prominent exception was the decreased concentration of mannose in keloid fibroblast cultures. In addition, glucose concentration in culture medium of keloid fibroblasts was constantly very low except in mannose-treated cultures where the consumption of glucose was dose-dependently decreased compared to increased mannose concentration. Similarly, increased concentrations of galactose and mannose resulted in dose-dependent lowered consumption of glucose in granulation tissue and hypertrophic scar fibroblasts. These findings suggest that the sugar metabolism may differ in various fibroblast cultures. Further, at least in our wound model, only glucose and mannose are present in wound fluid, and excess sugar is rapidly cleared from wound fluid.
Expression and phosphorylation of insulin receptor substrate 1 during rat liver regeneration. (1993)

Insulin has been shown to be important for normal liver regeneration to occur. The mechanisms whereby insulin may exert its effects on hepatocyte growth, however, are still unknown. The rat and human insulin receptor substrate 1 (IRS-1) is a specific target molecule for the insulin receptor beta subunit kinase and will bind to signal transducing molecules containing Src homology 2 domains through its multiple tyrosyl phosphorylation (TP) sites. This investigation examined how IRS-1 may be involved in insulin action during hepatocyte growth induced by two-thirds partial hepatectomy. The TP of IRS-1 was strikingly enhanced prior to the major wave of hepatocyte DNA synthesis at 24 h; IRS-1 protein and mRNA expression increased in parallel to a lesser extent after partial hepatectomy. TP of insulin receptor beta subunit, which enhances its kinase activity toward IRS-1, was increased in association with TP of IRS-1. Finally, phosphatidylinositol 3-kinase, one of signal transducing molecules containing Src homology 2 domains, was associated with IRS-1 following TP in vivo. These observations suggest that IRS-1 protein may play an important role in transmitting the insulin signal to intracellular regulators involved in hepatocyte growth.
Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. (1999)

Cervical cancer emerges from cervical intraepithelial neoplasia (CIN) induced by high-risk HPV (HR-HPV) infections. However, the vast majority of CIN lesions regresses spontaneously, and only a few lesions persist or progress to invasive carcinoma. On the basis of morphological criteria, it is not possible to differentiate high-grade lesions that will regress or persist from those that inevitably will progress to invasive cancers. In most cervical carcinomas, human papillomavirus (HPV) genomes are integrated into host cell chromosomes and transcribed into mRNAs encompassing viral and cellular sequences. In contrast, in early preneoplastic lesions, HPV genomes persist as episomes, and derived transcripts contain exclusively viral sequences. Thus, detection of HPV transcripts derived from integrated HPV genomes may specifically indicate both CIN lesions at high risk for progression as well as invasive cervical cancers. Here, we established a protocol for the amplification of papillomavirus oncogene transcripts (APOT) from cervical specimens that allows us to distinguish episome- from integrate-derived HPV mRNAs. Cervical swab and biopsy samples from 549 patients attending outpatient clinics for cervical dysplasia were screened for the presence of HPV DNA, and 155 samples that were positive for either HPV type 16 (n = 143) or 18 (n = 12) were subjected to the APOT assay. In samples derived from normal cervical epithelia (n = 19) or low-grade cervical lesions (CIN I, n = 10), no integrate-derived HPV transcripts were found. In contrast, in 1 (5%) of 22 samples derived from CIN II lesions, in 10 (16%) of 64 samples from patients with CIN III lesions, and in 35 (88%) of 40 samples from patients with cervical cancer, integrate-derived HPV transcripts were detected. Thus, detection of integrate-derived HPV transcripts in cervical swabs or biopsy specimens by the APOT assay points to advanced dysplasia or invasive cervical cancer.
Gene Cloning and Characterization of Multiple Alkane Hydroxylase Systems inRhodococcusStrains Q15 and NRRL B-16531 (2002)

The alkane hydroxylase systems of two Rhodococcus strains (NRRL B-16531 and Q15, isolated from different geographical locations) were characterized. Both organisms contained at least four alkane monooxygenase gene homologs (alkB1, alkB2, alkB3, and alkB4). In both strains, the alkB1 and alkB2 homologs were part of alk gene clusters, each encoding two rubredoxins (rubA1 and rubA2; rubA3 and rubA4), a putative TetR transcriptional regulatory protein (alkU1; alkU2), and, in the alkB1 cluster, a rubredoxin reductase (rubB). The alkB3 and alkB4 homologs were found as separate genes which were not part of alk gene clusters. Functional heterologous expression of some of the rhodococcal alk genes (alkB2, rubA2, and rubA4 [NRRL B-16531]; alkB2 and rubB [Q15]) was achieved in Escherichia coli and Pseudomonas expression systems. Pseudomonas recombinants containing rhodococcal alkB2 were able to mineralize and grow on C(12) to C(16) n-alkanes. All rhodococcal alkane monooxygenases possessed the highly conserved eight-histidine motif, including two apparent alkane monooxygenase signature motifs (LQRH[S/A]DHH and NYXEHYG[L/M]), and the six hydrophobic membrane-spanning regions found in all alkane monooxygenases related to the Pseudomonas putida GPo1 alkane monooxygenase. The presence of multiple alkane hydroxylases in the two rhodococcal strains is reminiscent of other multiple-degradative-enzyme systems reported in Rhodococcus.
Computer-assisted analysis and perception of stereochemical features in organic molecules using the CHIRON program (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputer-assisted analysis and perception of stereochemical features in organic molecules using the CHIRON programStephen Hanessian, Jonathan Franco, Gilbert Gagnon, Dominic Laramee, and Benoit LaroucheCite this: J. Chem. Inf. Comput. Sci. 1990, 30, 4, 413–425Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ci00068a012https://doi.org/10.1021/ci00068a012research-articleACS PublicationsRequest reuse permissionsArticle Views83Altmetric-Citations22LEARN 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 options Get e-Alerts
Comparative Analyses of Mechanistic Differences Among Antiestrogens (1999)

Antiestrogens such as tamoxifen are one of the most effective methods of treating estrogen receptor (ERα) positive breast cancers; however, the effectiveness of this therapy is limited by the almost universal development of resistance to the drug. If antiestrogens are recognized differently by the cell as it has been suggested, then in disease conditions where tamoxifen fails to function effectively, a mechanistically different antiestrogen might yield successful results. Although many antiestrogens have been developed, a direct comparison of their mechanisms of action is lacking, thus limiting their utility. Therefore, to determine if there are mechanistic differences among available antiestrogens, we have carried out a comprehensive analysis of the molecular mechanisms of action of 4-hydroxy-tamoxifen (4OHT), idoxifene, raloxifene, GW7604, and ICI 182,780. Using a novel set of peptides that recognize different surfaces on ERα, we have found that following binding to ERα, each ligand induces a distinct ERα-ligand conformation. Furthermore, transcriptional assays indicate that each ERα-ligand complex is recognized distinctly by the transcription machinery, and consequently, antiestrogens vary in their ability to inhibit estradiol- and 4OHT-mediated activities. Relative binding assays have shown that the affinity of these ligands for ERα is not always representative of their inhibitory activity. Using this assay, we have also shown that the pharmacology of each antiestrogen is influenced differently by hormone binding proteins. Furthermore, GW7604, like ICI 182,780, but unlike the other antiestrogens evaluated, decreases the stability of the receptor. Overall, our results indicate that there are clear mechanistic distinctions among each of the antiestrogens studied. However, GW7604 and ICI 182,780 differ more significantly from tamoxifen than idoxifene and raloxifene. These data, which reveal differences among antiestrogens, should assist in the selection of compounds for the clinical regulation of ERα function.
Dietary unsaturated fatty acids in type 2 diabetes: higher levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic acid-rich olive oil diet. (2000)

This study suggests that, in type 2 diabetes, an oleic acid-rich Mediterranean-type diet versus a linoleic acid-enriched diet may reduce the risk of atherosclerosis by decreasing the number of chylomicron remnant particles.
Molecular Determinants of Arg-Gly-Asp Ligand Specificity for β3 Integrins (1997)

The Arg-Tyr-Asp (RYD) and Arg-Gly-Asp (RGD) sequences within the third complementarity-determining region of the heavy chain (H3) of murine recombinant Fab molecules OPG2 and AP7, respectively, are responsible for their specific binding to the platelet integrin alphaIIbbeta3. In this study, we evaluated the influence of divalent cation composition and single amino acid substitutions at key positions within H3 on the selectivity of these Fab molecules for integrin alphaIIbbeta3 versus the vitronectin receptor alphaVbeta3. The parent Fab molecule OPG2 (H3 sequence, HPFYRYDGGN) binds selectively to alphaIIbbeta3 and not at all to any other RGD-cognitive integrin, particularly alphaVbeta3, under any divalent cation conditions. The binding of the AP7 Fab molecule (HPFYRGDGGN) to alphaIIbbeta3 is not affected by the relative composition of calcium, magnesium or manganese. However, AP7 binding to alphaVbeta3, either expressed by M21 cells or as the purified integrin, is supported by manganese and inhibited by calcium. If the flanking asparagine 108 residue within the AP7 H3 loop is replaced by alanine (HPFYRGDGGA), the resulting Fab molecule AP7.4 binds selectively to alphaVbeta3 in a cation-dependent manner, but does not bind at all to alphaIIbbeta3 under any conditions. AP7.4 binding to alphaVbeta3 is supported by manganese, completely inhibited by calcium, and largely unaffected by magnesium. This behavior mimics that of the adhesive protein, osteopontin, another ligand that binds preferentially to alphaVbeta3. Despite these differences in specificity for alphaIIbbeta3 and alphaVbeta3, AP7 and AP7.4 remain selective for the beta3 integrins and do not bind to cell lines that express the RGD-cognitive integrins alphaVbeta5 or alpha5beta1. These results confirm that subtle changes in the amino acid composition immediately flanking the RGD or RYD motifs can have a profound effect on beta3 integrin specificity, most likely because they influence the juxtaposition of the arginine and aspartate side chains within the extended RGD loop sequence.
siSPOTR: a tool for designing highly specific and potent siRNAs for human and mouse (2012)

RNA interference (RNAi) serves as a powerful and widely used gene silencing tool for basic biological research and is being developed as a therapeutic avenue to suppress disease-causing genes. However, the specificity and safety of RNAi strategies remains under scrutiny because small inhibitory RNAs (siRNAs) induce off-target silencing. Currently, the tools available for designing siRNAs are biased toward efficacy as opposed to specificity. Prior work from our laboratory and others' supports the potential to design highly specific siRNAs by limiting the promiscuity of their seed sequences (positions 2-8 of the small RNA), the primary determinant of off-targeting. Here, a bioinformatic approach to predict off-targeting potentials was established using publically available siRNA data from more than 50 microarray experiments. With this, we developed a specificity-focused siRNA design algorithm and accompanying online tool which, upon validation, identifies candidate sequences with minimal off-targeting potentials and potent silencing capacities. This tool offers researchers unique functionality and output compared with currently available siRNA design programs. Furthermore, this approach can greatly improve genome-wide RNAi libraries and, most notably, provides the only broadly applicable means to limit off-targeting from RNAi expression vectors.
Principles of Clinical Trials (2009)

Clinical trials are experiments conducted on human subjects for the purpose of evaluating one or more therapeutic interventions. Observational studies on cancer patients can generate knowledge about cancer behavior, biologic determinants of outcome, and hypotheses about therapeutic benefit. However, observational studies cannot control for factors that might influence outcome. Only through clinical trials can therapeutic interventions be reliably assessed. All aspects of the study rationale, objectives, design, treatments, data requirements, statistical justification, and analysis plan are detailed in the protocol document. As a clinical trial is an experiment, it must begin with a hypothesis or question: What are the toxic and/or biologic effects of a treatment or intervention? What effect does an intervention have on rates of tumor response, or on time to relapse, progression or death? To be successful, a study must clearly define the primary question and outcome measure(s) of interest, utilize an appropriate design and sample size to address the question, and collect and analyze data according to prespecified criteria. Increasingly clinical studies are enriched by the addition of secondary end points including quality of life and biomarker studies. Furthermore, studies conducted on human subjects must comply with international standards of ethical review and conduct. Finally, at the conclusion of each trial the interpretation of its results should be undertaken in the context of preexisting knowledge in the particular clinical setting studied. This chapter addresses all such aspects of clinical trials in cancer patients.
Phase I Study of a Combination of Recombinant Tumor Necrosis Factor-α and Recombinant Interferon-γ in Cancer Patients (1989)

Combinations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-alpha (rTNF-alpha) and rIFN-gamma combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-alpha and rIFN-gamma by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks. The dose levels were 5/5, 10/5, 10/10, 25/10, 25/25, 50/25, 50/50, 75/50, and 75/75 micrograms/m2 per day of rTNF-alpha/rIFN-gamma. A minimum of 2 patients were entered sequentially at each dose level. If the first 2-week cycle of therapy was well tolerated, the dose was increased to the next highest dose level during the second 2-week cycle. Fever, chills, and fatigue were observed at all doses. Severity of symptoms corresponded to increasing dose levels. Although TNF is identical to a molecule known as "cachectin," the vast majority of our patients did not lose weight while on study. However, alterations in lipid metabolism occurred and were manifested by a median change in triglyceride values of +40 mg/dl (range, -130 to +318 mg/dl), and in cholesterol values of -30 mg/dl (range, -103 to +2 mg/dl). The maximum tolerated dose was 75 micrograms/m2 of rTNF-alpha combined with 50 micrograms/m2 of rIFN-gamma, with dose-limiting side effects being mainly constitutional symptoms. A dose-related suppression in granulocyte and platelet counts was observed. Hematologic parameters returned to baseline within 72 h after therapy was discontinued, and neither infection nor bleeding occurred. Ten of 22 evaluable patients had stable disease for a median of 8 weeks (range, 4-21 weeks); 12 patients showed progressive disease. This study will form the framework for phase II trials of rTNF-alpha and rIFN-gamma combination therapy.
A visual language for image processing (2002)

The visual language Contata is a simple, but powerful, programming environment for the KHOROS system. By providing a graphical interface to basic components in the form of block diagrams with which researchers in many fields are already familiar, Contata promotes experimentation and learning without the need for advanced programming skills. The syntax of the language is discussed. Language features such as control structures and hierarchy are discussed. An image processing library and interoperable data exchange format are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ire-1-dependent Transcriptional Up-regulation of a Lumenal Uridine Diphosphatase from Caenorhabditis elegans (2004)

Lumenal ecto-nucleoside tri- and di-phosphohydrolases (ENTPDases) of the secretory pathway of eukaryotes hydrolyze nucleoside diphosphates resulting from glycosyltransferase-mediated reactions, yielding nucleoside monophosphates. The latter are weaker inhibitors of glycosyltransferases than the former and are also antiporters for the transport of nucleotide sugars from the cytosol to the endoplasmic reticulum (ER) and Golgi apparatus (GA) lumen. Here we describe the presence of two cation-dependent nucleotide phosphohydrolase activities in membranes of Caenorhabditis elegans: one, UDA-1, is a UDP/GDPase encoded by the gene uda-1, whereas the other is an apyrase encoded by the gene ntp-1. UDA-1 shares significant amino acid sequence similarity to yeast GA Gda1p and mammalian UDP/GDPases and has a lumenal active site in vesicles displaying an intermediate density between those of the ER and GA when expressed in S. cerevisiae. NTP-1 expressed in COS-7 cells appeared to localize to the GA. The transcript of uda-1 but not those of two other C. elegans ENTPDase mRNAs (ntp-1 and mig-23) was induced up to 3.5-fold by high temperature, tunicamycin, and ethanol. The same effectors triggered the unfolded protein response as shown by the induction of expression of green fluorescent protein under the control of the BiP chaperone promoter and the UDP-glucose:glycoprotein glucosyltransferase. Up-regulation of uda-1 did not occur in ire-1-deficient mutants, demonstrating the role of this ER stress sensor in this event. We hypothesize that up-regulation of uda-1 favors hydrolysis of the glucosyltransferase inhibitory product UDP to UMP, and that the latter product then exits the lumen of the ER or pre-GA compartment in a coupled exchange with the entry of UDP-glucose, thereby further relieving ER stress by favoring protein re-glycosylation.