gebhart/patrepeval huggingface dataset:
Urinary excretion of isoflavonoids and the risk of breast cancer. (1999)

Isoflavonoids are a group of biologically active phytochemicals that humans are exposed to mainly through soy food intake. Because of the similar chemical structure of these compounds and estradiol, it has been hypothesized that isoflavonoids may be related to the risk of breast cancer. Overnight urine samples from 60 incident breast cancer cases and their individually matched controls were assayed for urinary excretion rates of five major isoflavonoids (daidzein, genistein, glycitein, equol, and O-desmethylangolensin) and total phenols. These subjects were from a large population-based case-control study conducted in Shanghai, and urine samples from breast cancer cases were collected before any cancer therapy to minimize the potential influence of the disease and its sequelae on study results. Urinary excretion of total phenols and all individual isoflavonoids, particularly glycitein, was substantially lower in breast cancer cases than controls. For total isoflavonoids, the mean excretion was 13.95 nmol/mg creatinine (SD, 20.76 nmol/mg creatinine) for cases and 19.52 nmol/mg creatinine (SD, 25.36 nmol/mg creatinine) for controls (P for difference = 0.04). The case-control difference was more evident when median levels of these compounds were compared, with the median excretion of all major isoflavonoids being 50-65% lower in cases than in controls. Individuals in the highest tertile of daidzein, glycitein, and total isoflavonoids had about half the cancer risk of those in the lowest tertile. The adjusted odds ratio for breast cancer was 0.14 (95% confidence interval, 0.02-0.88) for women whose urinary excretion of both phenol and total isoflavonoids was in the upper 50% compared with those in the lower 50%. The results from this study support the hypothesis that a high intake of soy foods may reduce the risk of breast cancer.
Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequences in interphase human cells. (1995)

Coiled bodies (CBs) are nuclear organelles whose structures appear to be highly conserved in evolution. In rapidly cycling cells, they are typically located in the nucleoplasm but are often found in contact with the nucleolus. The CBs in human cells contain a unique protein, called p80-coilin. Studies on amphibian oocyte nuclei have revealed a protein within the "sphere" organelle that shares significant structural similarity to p80-coilin. Spheres and CBs are also highly enriched in small nuclear ribonucleoproteins and other RNA-processing components. We present evidence that, like spheres, CBs contain U7 small nuclear RNA (snRNA) and associate with specific chromosomal loci. Using biotinylated 2'-O-methyl oligonucleotides complementary to the 5' end of U7 snRNA and fluorescence in situ hybridization, we show that U7 is distributed throughout the nucleoplasm, excluding nucleoli, and is concentrated in CBs. Interestingly, we found that CBs often associate with subsets of the histone, U1, and U2 snRNA gene loci in interphase HeLa-ATCC and HEp-2 monolayer cells. However, in a strain of suspension-grown HeLa cells, called HeLa-JS1000, we found a much lower rate of association between CBs and snRNA genes. Possible roles for CBs in the metabolism of these various histone and snRNAs are discussed.
Dysregulation of Endogenous Opioid Emotion Regulation Circuitry in Major Depression in Women (2006)

The results demonstrate differences between women with MDD and control women in mu-opioid receptor availability during a neutral state, as well as opposite responses of this neurotransmitter system during the experimental induction of a sustained sadness state. These data demonstrate that endogenous opioid neurotransmission on mu-opioid receptors, a system implicated in stress responses and emotional regulation, is altered in patients diagnosed with MDD.
Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies (2014)

HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer; however, resistance to trastuzumab is common. The development of monoclonal antibodies that have complementary mechanisms of action results in a more comprehensive blockade of ErbB2 signaling, especially HER2/HER3 signaling. Use of such antibodies may have clinical benefits if these antibodies can become widely accepted. Here, we describe a novel anti-HER2 antibody, hHERmAb-F0178C1, which was isolated from a screen of a phage display library. A step-by-step optimization method was employed to maximize the inhibitory effect of this anti-HER2 antibody. Crystallographic analysis was used to determine the three-dimensional structure to 3.5 Å resolution, confirming that the epitope of this antibody is in domain III of HER2. Moreover, this novel anti-HER2 antibody exhibits superior efficacy in blocking HER2/HER3 heterodimerization and signaling, and its use in combination with pertuzumab has a synergistic effect. Characterization of this antibody revealed the important role of a ligand binding site within domain III of HER2. The results of this study clearly indicate the unique potential of hHERmAb-F0178C1, and its complementary inhibition effect on HER2/HER3 signaling warrants its consideration as a promising clinical treatment.
Recognition of duplex RNA by the deaminase domain of the RNA editing enzyme ADAR2 (2015)

Adenosine deaminases acting on RNA (ADARs) hydrolytically deaminate adenosines (A) in a wide variety of duplex RNAs and misregulation of editing is correlated with human disease. However, our understanding of reaction selectivity is limited. ADARs are modular enzymes with multiple double-stranded RNA binding domains (dsRBDs) and a catalytic domain. While dsRBD binding is understood, little is known about ADAR catalytic domain/RNA interactions. Here we use a recently discovered RNA substrate that is rapidly deaminated by the isolated human ADAR2 deaminase domain (hADAR2-D) to probe these interactions. We introduced the nucleoside analog 8-azanebularine (8-azaN) into this RNA (and derived constructs) to mechanistically trap the protein-RNA complex without catalytic turnover for EMSA and ribonuclease footprinting analyses. EMSA showed that hADAR2-D requires duplex RNA and is sensitive to 2'-deoxy substitution at nucleotides opposite the editing site, the local sequence and 8-azaN nucleotide positioning on the duplex. Ribonuclease V1 footprinting shows that hADAR2-D protects ∼ 23 nt on the edited strand around the editing site in an asymmetric fashion (∼ 18 nt on the 5' side and ∼ 5 nt on the 3' side). These studies provide a deeper understanding of the ADAR catalytic domain-RNA interaction and new tools for biophysical analysis of ADAR-RNA complexes.
Miniature swine as organ donors for man: Strategies for prevention of xenotransplant‐associated infections (1994)

Abstract: Xenotransplantation could potentially overcome limitations in organ transplantation resulting from a shortage of donor organs. Transplantation from miniature swine raises concerns over the potential introduction of new infectious agents into humans. These “direct zoonotic infections” or “xenoses” derived from swine fall into four categories: (1) microbial agents known to cause infection in humans (traditional zoonoses);(2) “species specific” organisms restricted to infection of the donor xenograft tissues by the absence of receptors or other factors needed for growth in human cells;(3) organisms of broad “host range” capable of infection of tissues outside the xenograft in the immunocompromised transplant recipient;and (4) organisms, such as retroviruses, of unknown quantity and with unmeasured capacity for causing disease in humans. The behavior of donor‐derived xenoses in immunocompromised xenotransplant recipients cannot be predicted. The ability of human‐derived microbial agents to infect porcine xenografts, and the capacity of the human immune system to inhibit such infections, also merit investigation. Experimental assessment of the infectious disease risks associated with xenotransplantation is important and practical.
Automation of high-throughput PCR assays (1996)

Many approaches to high-throughput genomic mapping and sequencing rely on variations of polymerase chain reaction (PCR)-based assays. Principal among these are radiation hybrid mapping, sequence-tagged sites (STS) content mapping, and transposon mapping. When applied on a genome-wide basis, the scope of the projects requires that the assays be automated to the greatest extent possible. In the following article, the application of various types of PCR-based assays will be presented together with brief descriptions of the various approaches to large-scale implementation. A detailed discussion of the approach to automation of PCR-based transposon mapping as used in our laboratory will then be presented. © 1996 John Wiley & Sons, Inc.
Design, Synthesis, and Biological Evaluation of 6-Substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones:  A Novel Class of Diarylheterocyclic Selective Cyclooxygenase-2 Inhibitors (2003)

A group of 6-alkyl (alkoxy or alkylthio)-4-aryl-3-(4-methanesulfonylphenyl)pyran-2-ones (14a-v), possessing either a H or F substituent at the para-position of the C-4 phenyl ring, were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo antiinflammatory-analgesic activities. Although 6-ethylthio-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14s) exhibited a very high in vitro COX-2 inhibitory potency (IC(50) = 0.0032 muM) and COX-2 selectivity (SI > 120 000), 14s exhibited moderate antiinflammatory activity compared to celecoxib in a carrageenan-induced rat paw edema assay. In contrast, the less potent (IC(50) = 0.10 muM), and less selective (SI = 2880) COX-2 inhibitor 6-ethoxy-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14i) exhibited good antiinflammatory activity where a 1 mg/kg oral dose reduced inflammation 32 and 67% at 3 and 5 h postdrug administration relative to the reference drug celecoxib where a 50 mg/kg oral dose reduced inflammation by 79 and 58% at the respective 3 and 5 h time periods. Molecular modeling studies, where 14i was docked in the active site of both COX-1 and COX-2, reveals that the C-6 ethoxy substituent orients the pyran-2-one ring to position the SO(2)Me pharmacophore in the vicinity of the secondary pocket in COX-2. The absence of this COX-2 secondary pocket in the COX-1 binding site is due to the presence of the bulky Ile(523) in COX-1 such that access to the amino acid residues (Ile(517), Phe(518), Gln(192), and His(90)), which line the COX-2 secondary pocket with which the SO(2)Me pharmacophore could interact, is hindered. The six-membered pyran-2-one ring system is a suitable central template to design selective COX-2 inhibitors.
Characterization of Binding of Candida albicans to Small Intestinal Mucin and Its Role in Adherence to Mucosal Epithelial Cells (2000)

In order to approximate and adhere to mucosal epithelial cells, Candida must traverse the overlying mucus layer. Interactions of Candida species with mucin and human buccal epithelial cells (BECs) were thus investigated in vitro. Binding of the Candida species to purified small intestinal mucin showed a close correlation with their hierarchy of virulence. Significant differences (P < 0.05) were found among three categories of Candida species adhering highly (C. dubliniensis, C. tropicalis, and C. albicans), moderately (C. parapsilosis and C. lusitaniae) or weakly (C. krusei and C. glabrata) to mucin. Adherence of C. albicans to BECs was quantitatively inhibited by graded concentrations of mucin. However, inhibition of adherence was reversed by pretreatment of mucin with pronase or C. albicans secretory aspartyl proteinase Sap2p but not with sodium periodate. Saturable concentration- and time-dependent binding of mucin to C. albicans was abrogated by pronase or Sap2p treatment of mucin but was unaffected by beta-mercaptoethanol, sodium periodate, neuraminidase, lectins, or potentially inhibitory sugars. Probing of membrane blots of the mucin with C. albicans revealed binding of the yeast to the 66-kDa cleavage product of the 118-kDa C-terminal glycopeptide of mucin. Although no evidence was found for the participation of C. albicans cell surface mannoproteins in specific receptor-ligand binding to mucin, inhibition of binding by p-nitrophenol (1 mM) and tetramethylurea (0.36 M) revealed that hydrophobic interactions are involved in adherence of C. albicans to mucin. These results suggest that C. albicans may both adhere to and enzymatically degrade mucins by the action of Saps, and that both properties may act to modulate Candida populations in the oral cavity and gastrointestinal tract.
Dog as an animal model for neurostimulation (1994)

The dog provides an important model to study the effect of neural stimulation of different parts of the central and peripheral nervous systems. A multitude of experiments on neurostimulation and neuromodulation to ensure bladder evacuation have been conducted on dogs. The present article reviews the most prominent contributions in the English literature related to neurostimulation using the dog as an experimental model. The various modes of stimulation using dogs as a model and the rationale for their use as well as their shortcomings will be examined. The prominent anatomic features in the neural control of the bladder and the technical aspects involved in neurostimulation of the canine bladder will be reviewed.
Synthesis and Thermal Behavior of Crystalline Hydrated Iron(III) Phosphates of Interest as Positive Electrodes in Li Batteries (2003)

Four different hydrated iron phosphates were prepared as pure crystalline powders by precipitation in aqueous solutions under controlled pH: strengite, FePO4·2H2O (Pbca; a = 9.8923(6) Å, b = 10.125(1) Å, c = 8.729(1) Å); metastrengite I, FePO4·2H2O (Pbnm; a = 5.226(2) Å, b = 10.026(3) Å, c = 8.917(3) Å); metastrengite II, FePO4·2H2O (P21/n; a = 5.3276(3) Å, b = 9.800(1) Å, c = 8.7129(6) Å, β = 90.532(6)°); and spheniscidite, NH4(Fe2(PO4)2OH·H2O)·H2O (P21/n; a = 9.808(3) Å, b = 9.727(3) Å, c = 9.866(3) Å, β = 102.85(2)°). Thermogravimetric analysis revealed slightly more than 2 H2O molecules per FePO4 for the first three compounds, the excess being considered as adsorbed on the powders' surface. Temperature-controlled X-ray diffraction allowed isolation and determination of the stability domains of a large number of FePO4 polymorphs which may, or may not, reabsorb H2O upon exposure to ambient air. All these phases, after careful optimization of the electrode preparation, may be reversibly reduced to ∼90% of their theoretical capacities within the 2−4 V vs Li+/Li region.
Cell Type-specific Regulation of Choline Acetyltransferase Gene Expression (1996)

This study demonstrates the presence of positive and negative regulatory elements within a 2336-base pair-long region of the rat choline acetyltransferase (ChAT) gene promoter that cooperate to direct cell type-specific expression in cholinergic cells. A 21-base pair-long neuron-restrictive silencer element (NRSE) was identified in the proximal part of this region. This element was recognized by the neuron-restrictive silencer factor (NRSF), previously shown to regulate expression of other neuron-specific genes. The ChAT NRSE was inactive in both cholinergic and non-cholinergic neuronal cells, but repressed expression from a heterologous promoter in non-neuronal cells. Specific deletion of this element allowed ChAT gene promoter activity in non-neuronal cells, and overexpression of NRSF repressed ChAT gene promoter activity in cholinergic cells. The distal part of the ChAT gene promoter showed cholinergic-specific enhancing activity, which stimulated promoter activity in cholinergic cells, but was inactive in non-cholinergic neuronal and non-neuronal cells. This enhancer region suppressed the activity of the ChAT NRSE in cholinergic cells, even after NRSF overexpression. Thus, at least two kinds of regulatory elements cooperate to direct ChAT gene expression to cholinergic neurons, namely a neuron-restrictive silencer element and a cholinergic-specific enhancer.
The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase (1999)

We have identified six protein kinases that belong to the family of cdc2-related kinases in Caenorhabditis elegans. Results from RNA interference experiments indicate that at least one of these kinases is required for cell-cycle progression during meiosis and mitosis. This kinase, encoded by the ncc-1 gene, is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and yeast CDC28/cdc2(+). We addressed whether ncc-1 acts to promote passage through a single transition or multiple transitions in the cell cycle, analogous to Cdks in vertebrates or yeasts, respectively. We isolated five recessive ncc-1 mutations in a genetic screen for mutants that resemble larval arrested ncc-1(RNAi) animals. Our results indicate that maternal ncc-1 product is sufficient for embryogenesis, and that zygotic expression is required for cell divisions during larval development. Cells that form the postembryonic lineages in wild-type animals do not enter mitosis in ncc-1 mutants, as indicated by lack of chromosome condensation and nuclear envelope breakdown. However, progression through G1 and S phase appears unaffected, as revealed by expression of ribonucleotide reductase, incorporation of BrdU and DNA quantitation. Our results indicate that C. elegans uses multiple Cdks to regulate cell-cycle transitions and that ncc-1 is the C. elegans ortholog of Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as mitotic cell cycles.
Enzyme-mediated enantioselective preparation of pure enantiomers of the antiviral agent 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC) and related compounds (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme-mediated enantioselective preparation of pure enantiomers of the antiviral agent 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC) and related compoundsLee K. Hoong, Luise E. Strange, Dennis C. Liotta, George W. Koszalka, Charlene L. Burns, and Raymond F. SchinaziCite this: J. Org. Chem. 1992, 57, 21, 5563–5565Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://doi.org/10.1021/jo00047a004RIGHTS & PERMISSIONSArticle Views525Altmetric-Citations79LEARN 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 InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Intragastric PCO2 in man and calculated gastric bicarbonate concentrations: effect of carbenoxolone sodium. (1980)

In six normal subjects, ten patients with either gastric or duodenal ulcer or combined duodenal and gastric ulcers and in one with gastric carcinoma, the fasting intragastric PCO2 was measured using a new silicon-coated teflon intragastric catheter connected to a mass spectrometer. PCO2 values ranged from 9 to 38 mm Hg in normal subjects and from 23 to 75 mm Hg in patients. In some patients sharp peaks up to 170 mm Hg were obtained. The pH of the resting juice was measured and the intragastric HCO-3 concentration calculated using the Henderson-Hasselbach equation. Intragastric HCO-3 concentration was 5--136 nmol per litre in normals and 12 nmol-960 mumol per litre in those with dyspepsia, and 6.05 mmol per litre in the patient with gastric carcinoma. Five dyspeptic patients and the one with stomach cancer were given 100 mg carbenoxolone t.d.s. for 72 hours. The fasting PCO2 decreased from a mean of 34.6 +/- 4.89 to 26.6 +/- 2.24 Se mmHg (p less than 0.05) with corresponding changes in HCO-3 concentration. These results suggest that carbenoxolone increased the thickness of the unstirred layer of mucus, making it more resistant to H+ penetration and thus reducing H+ and HCO-3 interaction with consequent lowering of PCO2.
Partitioning and Placement Technique for CMOS Gate Arrays (1987)

This paper describes an automatic partitioning and placement system for CMOS gate arrays utilizing two different kinds of data: circuit structure and hierarchical design data. Characteristic circuit structures such as the bus structure and the iterative structure are automatically extracted and handled like single cells in the placement process. The partitioning process has employed two processes: one is the bottom-up extraction of these structures, and the other is the top-down process, which divides the given circuit into several subcircuits. Making use of the partitioning results, the placement program is also carried out by two-level processes: subcircuit-level placement and cell-level placement. Through experiments, it has been proved that the proposed technique is effective for attaining better layout results.
Production by and isolation of exopolysaccharides from Streptococcus thermophilus grown in a milk medium and evidence for their growth-associated biosynthesis (1998)

Four Streptococcus thermophilus strains (Strep. thermophilus BTC, Strep. thermophilus LY03, Strep. thermophilus 480 and Strep. thermophilus Sfi20) have been examined for their exopolysaccharide production capacity. All strains produced a polymer composed of the neutral sugars glucose and galactose, but in different ratios. It was clearly shown that the biosynthesis of exopolysaccharides from Strep. thermophilus LY03 is growth-associated and hence displays primary metabolite kinetics. The monomer ratio of the exopolysaccharide synthesized did not vary throughout the fermentation cycle. The production kinetics and exopolysaccharide yields were strongly dependent on the fermentation conditions. Physical factors such as temperature, pH and oxygen tension as well as chemical factors (medium composition, initial lactose concentration, carbon/nitrogen levels) were of utmost importance.