gebhart/patrepeval huggingface dataset:
Reasoning about naming systems (1993)

article Free AccessReasoning about naming systems Authors: Mic Bowman Pennsylvania State Univ., University Park Pennsylvania State Univ., University ParkView Profile , Saumya K. Debray Univ. of Arizona, Tucson Univ. of Arizona, TucsonView Profile , Larry L. Peterson Univ. of Arizona, Tucson Univ. of Arizona, TucsonView Profile Authors Info & Claims ACM Transactions on Programming Languages and SystemsVolume 15Issue 5pp 795–825https://doi.org/10.1145/161468.161471Published:01 November 1993Publication History 167citation1,612DownloadsMetricsTotal Citations167Total Downloads1,612Last 12 Months112Last 6 weeks7 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
Safety and Feasibility of Catheter-Based Local Intracoronary Vascular Endothelial Growth Factor Gene Transfer in the Prevention of Postangioplasty and In-Stent Restenosis and in the Treatment of Chronic Myocardial Ischemia (2003)

Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.
A plasma lipoprotein containing only apolipoprotein Eand with gamma mobility on electrophoresis releases cholesterol fromcells. (1994)

Previous studies have identified lipid-poor high density lipoproteins with electrophoretic pre-beta mobility as the initial acceptors of cell-derived cholesterol in human plasma. These lipoproteins contain apolipoprotein A-I (apo A-I) as their sole apolipoprotein. In the present study, incubation of human plasma with [3H]cholesterol-laden skin fibroblasts has led to the identification of another lipoprotein that serves as a potent initial acceptor of cell-derived cholesterol. This lipoprotein, which we term gamma-LpE, exhibits gamma mobility on agarose gel electrophoresis. As determined by nondenaturing PAGE and by electron microscopy, the size of the spherical particle ranges between 12 and 16 nm. SDS/PAGE and subsequent immunoblotting identified apoE as its sole apolipoprotein. Plasma from normal and apoA-I-deficient mice, but not from apoE-deficient mice, released [3H]cholesterol from fibroblasts into a gamma-migrating lipoprotein. Cell culture media from hepatoma cells or mouse peritoneal macrophages, both of which contain apoE of cellular origin, also promoted efflux of [3H]cholesterol from fibroblasts into a gamma-migrating fraction. This was not observed with cell culture medium from fibroblasts alone. In conclusion, our results strongly indicate the presence in human plasma of a lipoprotein containing only apoE, gamma-LpE, which is secreted by peripheral cells and is a potent acceptor of cell-derived cholesterol.
Solid Phase Synthesis (Nobel Lecture) (1985)

A solid phase as “protecting group” in peptide synthesis —this was the original idea of Bruce Merrifield , who received the 1984 Nobel Prize for Chemistry. In his lecture, he describes the development of the Merrifield synthesis. In principle, all difunctional educts that may be selectively protected at one end and activated at the other can undergo reactions on solid supports.
Activation and Characterization of Procarboxypeptidase B from Human Plasma (1995)

Recently we reported the isolation and cloning of a novel plasma procarboxypeptidase B that binds plasminogen [Eaton, D. L., Malloy, B. E., Tsai, S. P., Henzel, W., & Drayna, D. (1991) J. Biol. Chem. 266, 21833-21838]. This plasma procarboxypeptidase is structurally similar to tissue procarboxypeptidases, and initial substrate studies showed that this plasma protein behaves like a basic carboxypeptidase and is now known as human plasma procarboxypeptidase B (pro-pCPB). However, unlike the tissue procarboxypeptidases, pro-pCPB is extremely unstable to trypsin activation. Trypsin cleaves pro-pCPB at two sites: Arg-92 and Arg-330. Cleavage at Arg-92 releases the activation peptide and generates an active enzyme. However, cleavage at Arg-330 inactivates pCPB. This renders the characterization of pCPB difficult. We have found that 6-amino-n-hexanoic acid (epsilon ACA), a compeptitive inhibitor of basic carboxypeptidases, selectively limits trypsin cleavage of pro-pCPB. In the presence of epsilon ACA, trypsin cleavage at Arg-330 is significantly limited while the cleavage at Arg-92 is unaffected. Using this approach, active pCPB can now be obtained. Kinetic characterization shows that pCPB behaves like other known basic carboxypeptidases. pCPB is more specific for substrates with C-terminal arginine than those with C-terminal lysine for all the natural and synthetic peptides tested. It also hydrolyzes the synthetic ester substrate more efficiently than the synthetic peptide substrate, especially at high pH. The active site Zn2+ can be replaced with other metals with change in substrate specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
Etude du mécanisme de la réaction des dérivés phosphométhyléniques et des phosphobétaïnes avec le benzaldéhyde (1963)

Abstract In the reaction between triphenyl phosphomethylene and benzaldehyde, the decomposition of the intermediate betaine is very slow compared with its rate of formation, and at 40° in chloroform, the dissociation of the betaine into the initial reactants can be followed. On the other hand, the first stage in the reaction between betaines of the type, Ph 3 PCHCOR, and benzaldehyde is the slow one. The rate of reaction is determined by the p Ka of the corresponding phosphonium salt according to the B RÖNSTED catalysis law.
Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies from patients with Sjogren's syndrome. (1986)

Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. To determine whether Epstein-Barr virus (EBV) might play a role in the pathogenesis of this disorder, we used monoclonal antibodies and DNA probes to detect evidence of viral gene products and genomes in these patients' tissue biopsies and saliva. Cytoplasmic staining of epithelial cells (i.e., ductal and/or acinar cells) with monoclonal antibody against the EBV-encoded early antigen (EA-D) was noted in 8/14 salivary gland biopsies from SS patients. This antibody did not react with normal salivary glands or salivary gland tumors, nor with other tissues from SS patients. The reactive antigen in SS biopsies had a m.w. of 52,000 on the basis of immunoblotting experiments, similar to the EA-D antigen found in lymphoblastoid cells lytically infected with EBV. EBV DNA was detected in parotid biopsies from two SS patients in amounts ranging from 0.1 to 3 pg per 20 micrograms of cellular DNA. Southern blotting was used to demonstrate the reactivity with Bam V, Eco D, and Bam M probes. Parotid saliva samples from 8/20 SS patients contained EBV DNA detectable by slot blot hybridization. EBV DNA was not detected in saliva of age-matched controls, rheumatoid arthritis patients lacking sicca symptoms, or patients with benign parotid tumors. The presence of EBV in salivary gland and saliva samples was associated with clinically more severe SS, as manifested by extraglandular symptoms such as vasculitis, occurrence of "pseudolymphoma", and marked abnormalities in immunoglobulin levels. These results demonstrate an elevated content of EBV in salivary glands of SS patients, and suggest that this virus may play a role in pathogenesis.
Cancer Treatment by Targeted Drug Delivery to Tumor Vasculature in a Mouse Model (1998)

In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides-one containing an alphav integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif-enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.
Oral Retinoids in the Treatment of Seborrhoea and Acne (1998)

Isotretinoin is an extremely effective drug if given systemically in severe forms of seborrhoea and acne, being the only retinoid with potent sebostatic properties. Its unique activity on the sebaceous gland still remains unclear since isotretinoin barely binds to cellular retinoic-acid-binding proteins and to retinoic acid receptors. Its bioavailability is approximately 25% and can be increased by food 1.5-2 times; after 30 min, the drug is detectable in the blood and maximal concentrations are reached 2-4 h after oral intake. The major metabolites of isotretinoin in blood are 4-hydroxy- and 4-oxo-isotretinoin, while several glucuronides are detectable in the bile. 4-Oxo-isotretinoin is present in plasma in a 2- to 4-fold higher concentration 6 h after a single dose. Steady-state concentrations appear after 1 week. The half-life elimination rate of the parent compound ranges from 7 to 37 h while that of some metabolites does so from 11 to 50 h. Isotretinoin crosses the placenta and is recognized as a strong teratogenic compound. About 10-30% of the drug is metabolized via its isomer tretinoin. Excretion of isotretinoin occurs after conjugation with the faeces or after metabolization with the urine. The epidermal levels of isotretinoin are rather low and no progressive accumulation, either in serum or in the skin, is found. After discontinuation of therapy, isotretinoin disappears from serum and skin within 2-4 weeks. Isotretinoin is the most effective drug in reducing sebaceous gland size (up to 90%) by decreasing proliferation of basal sebocytes, suppressing sebum production and inhibiting sebocyte differentiation in vivo. The molecular basis for its antisebotrophic activity has not been fully elucidated. Isotretinoin also exhibits anti-inflammatory activities. Systemic isotretinoin is today the regimen of choice in severe seborrhoea, since it reduces sebocyte lipid synthesis by 75% with daily doses as low as 0.1 mg/kg after 4 weeks. Patients who have received oral isotretinoin therapy for seborrhoea do not usually experience a relapse for months or years. In severe acne, a 6- to 12-month treatment with isotretinoin 1 mg/kg/day reduced to 0.5 or 0.2 mg/kg/day according to the response is recommended (cumulative dose of > 120 mg/kg). Contraception is essential during isotretinoin treatment in women of childbearing age 1 month before, during and for 3 months after discontinuation of treatment.
Identification of Novel Small‐molecule Inducers of Fetal Hemoglobin Using Pharmacophore and ‘PSEUDO’ Receptor Models (2006)

Pharmacologic reinduction of the developmentally silenced fetal (gamma) globin genes has been achieved in hemoglobinopathy patients using short chain fatty acid derivatives, with therapeutic effects. However, higher-potency inducers than are available in currently identified short chain fatty acid derivatives are desirable for long-term use. Using several short-chain fatty acids with established gamma-globin induction activity, a pharmacophore template was constructed with the TFIT module of the flo software and used to select several new candidate compounds, three of which exhibited significant activity in a gamma-globin gene reporter transcriptional assay which detects only strong inducers. The data were used to construct a new pharmacophore and a 'pseudo' receptor around it. Six hundred and thirty low-molecular weight compounds were docked into this receptor model. Of 26 compounds selected and tested in functional assays, two compounds showed activity >500% over control levels and two had activity 200% over control range, significantly more active than previously identified short chain fatty acid derivative fetal globin gene inducers. Three compounds had less activity; the remainder showed moderate activity. These findings demonstrate the feasibility of using iterative construction of pharmacophores, pseudo-binding site modeling, and virtual screening to identify small molecules with the ability to induce transcription of specific target genes, for potential therapeutics.
DAXX / ATRX , MEN1 , and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors (2011)

Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.
The Transforming Acidic Coiled Coil 3 Protein Is Essential for Spindle-dependent Chromosome Alignment and Mitotic Survival (2007)

Cancer-associated centrosomal transforming acidic coiled coil (TACC) proteins are involved in mitotic spindle function. By employing gene targeting, we have recently described a nonredundant and essential role of TACC3 in regulating cell proliferation. In this study, we used an inducible RNA interference approach to characterize the molecular function of TACC3 and its role in mitotic progression and cell survival. Our data demonstrate that a TACC3 knockdown arrests G(1) checkpoint-compromised HeLa cells prior to anaphase with aberrant spindle morphology and severely misaligned chromosomes. Interestingly, TACC3-depleted cells fail to accumulate the mitotic kinase Aurora B and the checkpoint protein BubR1 to normal levels at kinetochores. Moreover, localization of the structural protein Ndc80 at outer kinetochores is reduced, indicating a defective kinetochore-microtubule attachment in TACC3-deficient cells. As a consequence of prolonged TACC3 depletion, cells undergo caspase-dependent cell death that relies on a spindle checkpoint-dependent mitotic arrest. TACC3 knockdown cells that escape from this arrest by mitotic slippage become highly polyploid and accumulate supernumerary centrosomes. Similarly, deficiency of the post-mitotic cell cycle inhibitor p21(WAF) exacerbates the effects of TACC3 depletion. Our findings therefore point to an essential role of TACC3 in spindle assembly and cellular survival and identify TACC3 as a potential therapeutic target in cancer cells.
WebTables (2008)

The World-Wide Web consists of a huge number of unstructured documents, but it also contains structured data in the form of HTML tables. We extracted 14.1 billion HTML tables from Google's general-purpose web crawl, and used statistical classification techniques to find the estimated 154M that contain high-quality relational data. Because each relational table has its own "schema" of labeled and typed columns, each such table can be considered a small structured database. The resulting corpus of databases is larger than any other corpus we are aware of, by at least five orders of magnitude. We describe the WEBTABLES system to explore two fundamental questions about this collection of databases. First, what are effective techniques for searching for structured data at search-engine scales? Second, what additional power can be derived by analyzing such a huge corpus? First, we develop new techniques for keyword search over a corpus of tables, and show that they can achieve substantially higher relevance than solutions based on a traditional search engine. Second, we introduce a new object derived from the database corpus: the attribute correlation statistics database (AcsDB) that records corpus-wide statistics on co-occurrences of schema elements. In addition to improving search relevance, the AcsDB makes possible several novel applications: schema auto-complete , which helps a database designer to choose schema elements; attribute synonym finding , which automatically computes attribute synonym pairs for schema matching; and join-graph traversal , which allows a user to navigate between extracted schemas using automatically-generated join links.
New Histamine H3-Receptor Ligands of the Proxifan Series:  Imoproxifan and Other Selective Antagonists with High Oral in Vivo Potency (2000)

Histamine H(3)-receptor antagonists of the proxifan series are described. The novel compounds possess a 4-(3-(phenoxy)propyl)-1H-imidazole structure and various functional groups, e.g., an oxime moiety, on the phenyl ring. Synthesis of the novel compounds and X-ray crystallography of one highly potent oxime derivative, named imoproxifan (4-(3-(1H-imidazol-4-yl)propyloxy)phenylethanone oxime), are described. Most of the title compounds possess high antagonist potency in histamine H(3)-receptor assays in vitro as well as in vivo in mouse CNS following po administration. Structure-activity relationships are discussed. Imoproxifan displays subnanomolar potency on a functional assay on synaptosomes of rat cerebral cortex (K(i) = 0.26 nM). In vivo, imoproxifan increases the central N(tau)-methylhistamine level with an ED(50) of 0.034 mg/kg po. A receptor profile on several functional in vitro assays was determined for imoproxifan, demonstrating high selectivity toward the histamine H(3) receptor for this promising candidate for further development.
Capturing native long-range contiguity by in situ library construction and optical sequencing (2012)

The relatively short read lengths associated with the most cost-effective DNA sequencing technologies have limited their use in de novo genome assembly, structural variation detection, and haplotype-resolved genome sequencing. Consequently, there is a strong need for methods that capture various scales of contiguity information at a throughput commensurate with the current scale of massively parallel sequencing. We propose in situ library construction and optical sequencing on the flow cells of currently available massively parallel sequencing platforms as an efficient means of capturing both contiguity information and primary sequence with a single technology. In this proof-of-concept study, we demonstrate basic feasibility by generating >30,000 Escherichia coli paired-end reads separated by 1, 2, or 3 kb using in situ library construction on standard Illumina flow cells. We also show that it is possible to stretch single molecules ranging from 3 to 8 kb on the surface of a flow cell before in situ library construction, thereby enabling the production of clusters whose physical relationship to one another on the flow cell is related to genomic distance.
Blind deconvolution for confocal laser scanning microscopy (2009)

La microscopie confocale à balayage laser est une technique puissante pour étudier les spécimens biologiques en trois dimensions (3D) par sectionnement optique. Bien qu ubiquitaire, il persiste des incertitudes dans le procédé d observations. Comme la réponse du système à l impulsion, ou fonction de flou (PSF), est dépendante à la fois du spécimen et des conditions d acquisition, elle devrait être estimée à partir des images observées avec l objet. Ce problème est mal posé, sous déterminé, et comme le processus de mesure est quasi-aléatoire dans la nature, nous le traitons en utilisant l interférence bayésienne. L état de l art des algorithmes concernant la déconvolution et déconvolution aveugle est exposé dans le cadre d un travail bayésien. Dans la première partie, nous constatons que la diffraction limitée de l objectif et le bruit intrinsèque, sont les distorsions primordiales qui affectent les images d un spécimen fin. Une approche de minimalisation alternative (AM), restaure les fréquences manquantes au-delà de la limite de diffraction, en utilisant une régularisation de la variation totale sur l objet, et une contrainte spatiale sur la PSF. En outre, des méthodes sont proposées pour assurer la positivité des intensités estimées, conserver le flux de l objet, et bien manier le paramètre de la régularisation. Quand il s agit d imager des spécimens épais, la phase de la fonction de la pupille, due à l aberration sphérique (SA) ne peut être ignorée. Dans la seconde partie, il est montré qu elle dépend de la discordance de l index de réfraction entre l objet et le milieu d immersion de l objectif et de la profondeur sur la lamelle. Les paramètres d imagerie et la distribution de l intensité originelle de l objet sont récupérés en modifiant les algorithmes AM. Due à l incohérence de la microscopie à fluorescence, la phase de récupération des intensités observées est possible en contraignant la phase par l utilisation d optiques géométriques. Cette méthode pourrait être étendue pour restituer des spécimens affectés par la SA. Comme la PSF varie dans l espace, un modèle de quasi-convolution est proposé, et la PSF est rendue approximative. Ainsi, en plus de l objet, il suffit d estimer un seul libre paramètre.
Structure of the rainbow trout metallothionein B gene and characterization of its metal-responsive region. (1988)

The trout metallothionein (MT) genes consist of two members. We describe the structure of the first fish MT (tMT-B) gene which shows an overall resemblance but some remarkable differences with mammalian MT genes. The similarities included (i) tripartite structure of the gene, (ii) conservation of cysteine residues, and (iii) a TATAAA signal and two copies of metal-responsive elements (MREs). The differences consisted of (i) an AT-rich tMT-B promoter compared with highly GC-rich mammalian MT promoters and (ii) a lack of SP1-binding sites in the tMT-B promoter. Functional analysis of the tMT-B 5'-flanking region following fusion with the bacterial chloramphenicol acetyltransferase gene and its transfection into the rainbow trout hepatoma cell line revealed that sequences from positions -600 to +8 are sufficient for regulation by metals. Further deletion analyses of this fragment suggested that a minimum of 100 nucleotides upstream of the transcription initiation site are required for induction by cadmium and zinc. The tMT-B promoter was also functional in the human hepatoblastoma cell line, suggesting that an MT regulatory factor(s) is conserved in phylogenetically distant species like humans and fish.