gebhart/patrepeval huggingface dataset:
Retraction: Blockage of intracellular proton extrusion with proton pump inhibitor induces apoptosis in gastric cancer (2007)

Proton pump inhibitors have been used for treatment of acid-related gastroesophageal diseases and they act as potent inhibitors of gastric acid pump, H(+)/K(+)-ATPase. Since cancer cells in vivo often exist in an ischemic microenvironment with a lower pH, maintenance of cellular pH is important for cell survival. In this study, we evaluated whether blocking of proton extrusion with proton pump inhibitors could inhibit the viability of gastric cancer cells. Treatment of human gastric cancer cells with proton pump inhibitors significantly attenuated cell viability in a time- and dose-dependent manner. The pro-apoptotic activity of proton pump inhibitors was mediated by release of cytochrome c and caspases activation. Gastric cancer cells showed the resistance to acidity of culture medium, which was related with a remarkable increase of extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation in the acidic condition. This ERK1/2 phosphorylation was completely inhibited by pretreatment with proton pump inhibitors, suggesting that its inhibitory action on phosphorylation of ERK1/2 might contribute to the induction of apoptosis in gastric cancer cells. In conclusion, our results suggest novel therapeutic approaches for gastric cancer with proton pump inhibitors.
Construction of an improved host strain for two hybrid screening (1994)

Journal Article Construction of an improved host strain for two hybrid screening Get access H.E. Feilotter, H.E. Feilotter Cold Spring Harbor Laboratory1 Bungtown Road, Cold Spring Harbor, NY 11724, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar G.J. Harmon, G.J. Harmon Cold Spring Harbor Laboratory1 Bungtown Road, Cold Spring Harbor, NY 11724, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar C.J. Ruddell, C.J. Ruddell Cold Spring Harbor Laboratory1 Bungtown Road, Cold Spring Harbor, NY 11724, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Beach D. Beach * Cold Spring Harbor Laboratory1 Bungtown Road, Cold Spring Harbor, NY 11724, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 22, Issue 8, 25 April 1994, Pages 1502–1503, https://doi.org/10.1093/nar/22.8.1502 Published: 25 April 1994 Article history Received: 16 February 1994 Revision received: 11 March 1994 Accepted: 11 March 1994 Published: 25 April 1994
Immunotherapy of Cancer with Nonliving BCG and Fractions Derived from Mycobacteria: Role of Cord Factor (Trehalose-6, 6′-Dimycolate) in Tumor Regression (1974)

Delipidated and deproteinized cell walls from Mycobacterium tuberculosis H37Ra suspended in 1.25% mineral oil emulsion cured established tumors in the skin and metastases in draining lymph nodes of guinea pigs (strain 2) after intratumoral administration in 33% of the cases examined. This was increased to 83% when a mixture of cord factor and the delipidated cell walls was used. A similarly high percentage of cures was obtained after administration of lyophilized, killed BCG alone or with addition of cord factor in 1% mineral oil emulsion. Lyophilized, killed BCG dispersed in a solution of tocopherol acetate in peanut oil or in peanut oil alone showed a limited tumor-regressive activity (36%). However, a mixture of BCG and cord factor suspended in the above media cured 80 and 69% of the treated animals, respectively.
Scalable Internet resource discovery (1994)

article Free Access Share on Scalable Internet resource discovery: research problems and approaches Authors: C. Mic Bowman Transarc Corp., The Gulf Tower, Pittsburgh, PA Transarc Corp., The Gulf Tower, Pittsburgh, PAView Profile , Peter B. Danzig Univ. of Southern California, Los Angeles Univ. of Southern California, Los AngelesView Profile , Udi Manber Univ. of Arizona, Tucson Univ. of Arizona, TucsonView Profile , Michael F. Schwartz Univ. of Colorado, Boulder Univ. of Colorado, BoulderView Profile Authors Info & Claims Communications of the ACMVolume 37Issue 8Aug. 1994 pp 98–ff.https://doi.org/10.1145/179606.179704Published:01 August 1994Publication History 127citation566DownloadsMetricsTotal Citations127Total Downloads566Last 12 Months27Last 6 weeks5 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Binding Model for Nonpeptide Antagonists of αvβ3 Integrin (2002)

A binding model for nonpeptide antagonists of integrin alpha(v)beta(3) has been developed through docking analyses utilizing the MMFFs force field and the recently published crystal structure, 1JV2. Results of this docking study have led to the identification of a novel binding model for selective antagonists of alpha(v)beta(3) over alpha(IIb)beta(3) integrins. Four different chemical classes are shown to bind in a similar fashion providing a measure of confidence in the proposed model. All alpha(v)beta(3) and alpha(IIb)beta(3) antagonists have a basic nitrogen separated some distance from a carboxylic acid to mimic RGD. For the alpha(v)beta(3) antagonists under present consideration, these charged ends are separated by twelve bonds. The basic nitrogen of the active alpha(v)beta(3) ligands are shown to interact with D150 of alpha(v) and the ligands' carboxylic acid interact with R214 of beta(3) while adopting an extended conformation with minimal protein induced internal strain. In addition, an energetically favorable interaction is found with all of the active alpha(v)beta(3) molecules with Y178 of alpha(v) when docked to the crystallographically determined structure. This novel interaction may be characterized as pi-pi stacking for the most active of the alpha(v)beta(3) selective antagonists. The proposed model is consistent with observed activity as well as mutagenicity and photoaffinity cross-linking studies of the alpha(v)beta(3) integrin.
MicroRNA-143 and -145 in Colon Cancer (2007)

MicroRNAs (miRNAs) are endogenous, small non-coding RNAs (20-22 nucleotides) that negatively regulate gene expression at the translational level by base pairing to the 3' untranslated region of target messenger RNAs. More than 400 miRNAs have been identified in humans and are evolutionally conserved from plants to animals. It has been revealed that miRNAs regulate various biological processes, such as development, cell differentiation, cell proliferation, and cell death. It is predicted that 30% of protein-encoding genes are regulated by miRNAs. Inappropriate expression of miRNAs has been found in cancer. Especially, the expression level of miRNAs that act like anti-oncogenes is frequently reduced in cancers because of chromosome aberrations. In addition, since the processing of miRNAs has been characterized to be enzymatic in nature, the expression levels of miRNAs are closely associated with the activity and levels of such enzymes. In this review, we discuss recent remarkable advances in miRNA biogenesis, bio-networking involving miRNAs, and their roles in carcinogenesis. Further, we discuss the expression of miRNA-143 and -145 in colon cancer and their roles in carcinogenesis. The available data suggest that miRNAs would be potentially useful as diagnostic and therapeutic tools.
Numerical analysis of the flow around a circular cylinder using RANS and LES (2006)

The present study is to simulate the flow past a circular cylinder at a Reynolds (Re) number of 5800, which is based on free-stream velocity and the cylinder diameter. The cylinder is slightly heated and the amount of heat is small enough to be considered as a passive scalar. Due to its complexity, the flow around a circular cylinder is considered as a challenging problem for computational fluid dynamics (CFD) simulation. Re-averaged Navier–Stokes (RANS) equations and large eddy simulation (LES) are two commonly used approaches in turbulent flow simulation. In this study, these two methods are both investigated by employing a CFD software called FLUENT. For two-dimensional (2D) simulation, the renormalization group k–ϵ model is used with enhanced wall treatment. Moreover, 2D LES is also tested, which reveals the necessity for three-dimensional (3D) LES computations. For 3D simulations, computations with the Smagorinsky–Lilly subgrid-scale (SGS) model and dynamic SGS model are used. A phase-averaging technique is employed to study turbulence structure in the circular cylinder wake. An instantaneous quantity is decomposed into a time-mean component, a coherent component and an incoherent component (Reynolds and Hussain Citation1972). After the triple decomposition and structural averaging, the coherent contributions to the Reynolds stresses and temperature variance can be analyzed. The reference phase for phase averaging is calculated for the time history of the lift coefficient CL. Both velocity field and temperature field are investigated and compared with the experimental measurements.
Neural networks applied to structure-activity relationships (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNeural networks applied to structure-activity relationshipsTomoo Aoyama, Yuji Suzuki, and Hiroshi IchikawaCite this: J. Med. Chem. 1990, 33, 3, 905–908Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/jm00165a004https://doi.org/10.1021/jm00165a004research-articleACS PublicationsRequest reuse permissionsArticle Views166Altmetric-Citations125LEARN 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
Feedback between p21 and reactive oxygen production is necessary for cell senescence (2010)

Cellular senescence--the permanent arrest of cycling in normally proliferating cells such as fibroblasts--contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of 'deep' cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype.
Novel Human Transitional B Cell Populations Revealed by B Cell Depletion Therapy (2009)

Transitional cells represent a crucial step in the differentiation and selection of the mature B cell compartment. Human transitional B cells have previously been variably identified based on the high level of expression of CD10, CD24, and CD38 relative to mature B cell populations and are expanded in the peripheral blood following rituximab-induced B cell-depletion at reconstitution. In this study, we take advantage of the gradual acquisition of the ABCB1 transporter during B cell maturation to delineate refined subsets of transitional B cells, including a late transitional B cell subset with a phenotype intermediate between T2 and mature naive. This late transitional subset appears temporally following the T1 and T2 populations in the peripheral compartment after rituximab-induced B cell reconstitution (and is thus termed T3) and is more abundant in normal peripheral blood than T1 and T2 cells. The identity of this subset as a developmental intermediate between early transitional and mature naive B cells was further supported by its ability to differentiate to naive during in vitro culture. Later transitional B cells, including T2 and T3, are found at comparatively increased frequencies in cord blood and spleen but were relatively rare in bone marrow. Additional studies demonstrate that transitional B cells mature across a developmental continuum with gradual up-regulation of mature markers, concomitant loss of immature markers, and increased responsiveness to BCR cross-linking in terms of proliferation, calcium flux, and survival. The characterization of multiple transitional B cell subpopulations provides important insights into human B cell development.
ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival (2011)

Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.
The Psychopharmacology of Appetite: Targets for Potential Anti-Obesity Agents (2003)

The escalating pandemic of obesity has generated demand for a new generation of novel anti-obesity agents. Over the past 8 years numerous systems within the CNS critical to the expression of appetite and energy regulation have been revealed. With increasing knowledge we seem tantalisingly close to producing an unprecedented range of anorectic agents capable of inducing sustained clinical weight loss. However, it remains essential to establish that any test compound reduces food intake by selectively acting on the endogenous appetite system (or by inducing nausea or malaise). Only drugs (agonist or antagonist) that modify the daily flux of appetite, for instance enhancing within meal satiation and strengthening post meal satiety, can be considered as appetite suppressants with clinical potential. Systems of interest include peripheral factors released episodically prior to, during and after the consumption of food, many of which have been shown to have receptors within the Central Nervous System (CNS). These include Glucagon-Like Peptide (GLP)-1, Cholecystokinin (CCK), Gastrin Releasing Peptides (GRP), Enterostatin, Amylin, Peptide YY (PYY) and most recently Ghrelin. The identification of the hormone leptin (the ob protein), a key signal linking adipose tissue status with key CNS regulatory circuits, was arguably the key event in the current revolution in appetite research. Leptin itself may be one of a much larger class of peripheral tonic signals, with receptors within the CNS, informing the brain of the bodys energy status and providing a second set of target systems. Collectively, these episodic and tonic signals appear to be integrated in key CNS circuits containing monoamine neurotransmitters (Serotonin - 5-HT, Nor-Adrenaline - NA, and Dopamine - DA) and numerous neuropeptides (Melanocortins, Neuropeptide Y - NPY, Orexins, Cocaine and Amphetamine Regulating Transcript - CART, Agouti Related Peptide - AgRP and Galanin) all of which could be selectively targeted to reduce food intake and induce weight loss. Food intake can also be adjusted by drugs such as the cannabiniods acting upon the hedonic components of eating behaviour. However, any drug targeting the aforementioned systems must produce changes in feeding behaviour such as meal patterns and food choice consistent with a selective action on appetite. Ultimately in humans, this will be expressed in changes in meal size, reduced snacking and possibly a selective reduction in the intake of calorie dense high fat foods.
[Livedo racemosa generalisata in atrial myxoma]. (1996)

We describe a patient with livedo racemosa generalisata (LRG), Raynaud's phenomenon, multifocal recurring transitory and complete ischemic attacks and laboratory findings of systemic inflammation. Working diagnoses were vasculitis, mixed connective tissue disease, or Sneddon's syndrome, but echocardiography revealed a left atrial myxoma. Special staining of skin biopsies with alcian-blue showed arterial occlusion caused by myxomatous material. Arterial embolism by parts of the myxoma is suggested to be the cause of the LRG and probably the neurological findings.
Juvenile onset Huntington's disease—clinical and research perspectives (2001)

Huntington's disease (HD) is an inherited neurodegenerative disorder. The mutation which causes the disease is an expansion in the number of repetitions of three nucleotides, C, A, and G in exon 1 of the huntingtin gene. The gene normally has 15 to 30 repeats and an expansion to 40 or more is associated with HD. HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases. Juvenile HD is characterized by (1) transmission from an HD affected father, (2) an unusually large repeat size, usually of 60 or more units, and (3) unique clinical features, including rigidity and seizure disorder. Although juvenile onset is associated with a more severe neuropathological involvement, the neuropathological characteristics of juvenile HD are similar to those seen in the adult form in that the striatum bears the brunt of the illness. Clumps of protein, termed inclusion bodies, which stain positive for huntingtin and ubiquitin, are found primarily in the nucleus but also in the cytoplasm and axons in HD neurons. Research suggests that these inclusion bodies sequester a deleterious protein fragment and prolong cell life during the degenerative process of the disease.
Development of a new introduction technique for the pulsatile catheter pump. (1997)

The pulsatile catheter (PUCA) pump is an intraventricular blood pump that can be introduced into the left ventricular cavity through a superficial artery (transarterially) or directly through the thoracic aorta during open chest conditions. When positioned, the pump aspirates blood from the left ventricle and transports it into the ascending aorta. A pneumatic driving system allows the blood to be ejected in early diastole of every second or third heart beat. The main goal of this study was to develop an easy, fast, safe surgical introduction technique. Four different means of catheter introduction were tested in 20 acute open chest experiments with calves: introduction without any guidance at all, introduction by x-ray guidance only, introduction using a guide wire plus x-ray guidance, and introduction using a guiding pressure catheter. Introducing the PUCA pump catheter into the left ventricular cavity using a pigtail guiding pressure catheter proved to be easy. The large bore pump catheter followed the guiding catheter and passed the aortic valve well. The position of the PUCA pump could be monitored from the pressure patterns derived from the guiding catheter.
Characterization of cDNA clones for the human c-yes gene. (1987)

Three c-yes cDNA clones were obtained from poly(A)+ RNA of human embryo fibroblasts. Sequence analysis of the clones showed that they contained inserts corresponding to nearly full-length human c-yes mRNA, which could encode a polypeptide of 543 amino acids with a relative molecular weight (Mr) of 60,801. The predicted amino acid sequence of the protein has no apparent membrane-spanning region or suspected ligand binding domain and closely resembles pp60c-src. Comparison of the sequences of c-yes and v-yes revealed that the v-yes gene contains most of the c-yes coding sequence except the region encoding its extreme carboxyl terminus. The region missing from the v-yes protein is the part that is highly conserved in cellular gene products of the protein-tyrosine kinase family.
Small-Molecule Inhibition of BRDT for Male Contraception (2012)

A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of a selective small-molecule inhibitor (JQ1) of the bromodomain and extraterminal (BET) subfamily of epigenetic reader proteins. Here, we report potent inhibition of the testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical and crystallographic studies confirm that occupancy of the BRDT acetyl-lysine binding pocket by JQ1 prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduced seminiferous tubule area, testis size, and spermatozoa number and motility without affecting hormone levels. Although JQ1-treated males mate normally, inhibitory effects of JQ1 evident at the spermatocyte and round spermatid stages cause a complete and reversible contraceptive effect. These data establish a new contraceptive that can cross the blood:testis boundary and inhibit bromodomain activity during spermatogenesis, providing a lead compound targeting the male germ cell for contraception.
Stereotactic radiosurgery for pituitary tumors (2003)

Pituitary adenomas frequently pose challenging clinical problems. Stereotactic radiosurgery (SRS) is one treatment option in selected patients. The purpose of this report is to identify the advantages and disadvantages of radiosurgery in cases of pituitary tumors to assess better its role in relation to other treatment. Methods for optimizing outcome are described. The author reviews several recent series to determine rates of growth control, endocrine response, and complications. In general, growth control is excellent, complications are very low, and reduction of excessive hormone secretion is fair. Depending on the clinical situation, SRS may be the treatment of choice in selected patients.
A Tailor‐Made Metallocene for the Copolymerization of Ethene with Bulky Cycloalkenes (1995)

Zirconocene/methylaluminoxane catalysts made-to-measure (with zirconocenes such as 1) facilitate statistical incorporation of bulky cycloolefins such as dimethanooctahydronapthalene into a polyethylene chain. The new cycloolefin copolymers are extremely thermally stable and show very promising properties for optoelectronic and technical applications.
Changes in the distribution pattern of Claudin tight junction proteins during the progression of mouse skin tumorigenesis (2007)

This is the first demonstration of the changes in Cldn expression in the progression of DMBA/TPA-induced skin tumors; however further investigation into the molecular mechanisms regulating the observed changes in barrier selectivity during tumorigenesis is required.
ChemInform Abstract: Reactions of Polyfluoroalkyl o‐Nitrobenzenesulfonates with Tertiary Amines. (1986)

Abstract Die Reaktionen der Nitrobenzolsulfonate (I) mit verschiedenen tertiären Aminen zur Synthese von Fluor enthaltenden tertiären Aminen werden untersucht.