gebhart/patrepeval huggingface dataset:
Higher expression of circulating miR-182 as a novel biomarker for breast cancer (2013)

MicroRNAs (miRNAs), present in the serum in a stable and reproducible manner, may be used as biomarkers for various diseases. Few studies have previously investigated circulating miRNAs in the peripheral blood of breast cancer (BC) patients. To identify the role of serum miR-182 levels in BC, the present study detected miR-182 levels in the serum of 46 BC patients and 58 controls, by quantitative PCR. The results showed that the serum miR-182 levels in BC patients were significantly higher compared with the serum of healthy controls (P<0.01). The miR-182 was also overexpressed in the BC tissues compared with the para-carcinoma tissues. Furthermore, the serum levels of miR-182 in the estrogen receptor (ER)-positive patients were considerably lower compared with those in the ER-negative patients. The serum levels of miR-182 in the progesterone receptor (PR)-positive patients were also found to be lower compared with those in the PR-negative patients. The current study highlights results consistent with miR-182 as a novel and valuable biomarker for the diagnosis of BC.
Identification of a New Family of Genes Involved in β-1,2-Mannosylation of Glycans in Pichia pastoris and Candida albicans (2008)

Structural studies of cell wall components of the pathogenic yeast Candida albicans have demonstrated the presence of beta-1,2-linked oligomannosides in phosphopeptidomannan and phospholipomannan. During C. albicans infection, beta-1,2-oligomannosides play an important role in host/pathogen interactions by acting as adhesins and by interfering with the host immune response. Despite the importance of beta-1,2-oligomannosides, the genes responsible for their synthesis have not been identified. The main reason is that the reference species Saccharomyces cerevisiae does not synthesize beta-linked mannoses. On the other hand, the presence of beta-1,2-oligomannosides has been reported in the cell wall of the more genetically tractable C. albicans relative, P. pastoris. Here we present the identification, cloning, and characterization of a novel family of fungal genes involved in beta-mannose transfer. Employing in silico analysis, we identified a family of four related new genes in P. pastoris and subsequently nine homologs in C. albicans. Biochemical, immunological, and structural analyses following deletion of four genes in P. pastoris and deletion of four genes acting specifically on C. albicans mannan demonstrated the involvement of these new genes in beta-1,2-oligomannoside synthesis. Phenotypic characterization of the strains deleted in beta-mannosyltransferase genes (BMTs) allowed us to describe the stepwise activity of Bmtps and acceptor specificity. For C. albicans, despite structural similarities between mannan and phospholipomannan, phospholipomannan beta-mannosylation was not affected by any of the CaBMT1-4 deletions. Surprisingly, depletion in mannan major beta-1,2-oligomannoside epitopes had little impact on cell wall surface beta-1,2-oligomannoside antigenic expression.
The Protein Kinase Cβ–Selective Inhibitor, Enzastaurin (LY317615.HCl), Suppresses Signaling through the AKT Pathway, Induces Apoptosis, and Suppresses Growth of Human Colon Cancer and Glioblastoma Xenografts (2005)

Activation of protein kinase Cbeta (PKCbeta) has been repeatedly implicated in tumor-induced angiogenesis. The PKCbeta-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Activation of PKCbeta has now also been implicated in tumor cell proliferation, apoptosis, and tumor invasiveness. Herein, we show that Enzastaurin has a direct effect on human tumor cells, inducing apoptosis and suppressing the proliferation of cultured tumor cells. Enzastaurin treatment also suppresses the phosphorylation of GSK3betaser9, ribosomal protein S6(S240/244), and AKT(Thr308). Oral dosing with Enzastaurin to yield plasma concentrations similar to those achieved in clinical trials significantly suppresses the growth of human glioblastoma and colon carcinoma xenografts. As in cultured tumor cells, Enzastaurin treatment suppresses the phosphorylation of GSK3beta in these xenograft tumor tissues. Enzastaurin treatment also suppresses GSK3beta phosphorylation to a similar extent in peripheral blood mononuclear cells (PBMCs) from these treated mice. These data show that Enzastaurin has a direct antitumor effect and that Enzastaurin treatment suppresses GSK3beta phosphorylation in both tumor tissue and in PBMCs, suggesting that GSK3beta phosphorylation may serve as a reliable pharmacodynamic marker for Enzastaurin activity. With previously published reports, these data support the notion that Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis.
Discordance Between HbA1c and Fructosamine (2003)

The glycosylation gap may be a useful clinical research tool for evaluating physiologic sources of variation in diabetic complications beyond glycemic control.
Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma (2008)

Ribonucleases are a superfamily of enzymes which operate at the crossroads of transcription and translation, catalyzing the degradation of RNA; they can be cytotoxic because the cleavage of RNA renders indecipherable its information. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models. The maximum tolerated dose emerging from phase I studies was 960 g/m(2), with renal toxicity as the main dose-limiting toxicity. A large phase II trial showed that ranpirnase has disease-modifying activity against malignant mesothelioma. Ranpirnase proved to be superior to doxorubicin in a phase III trial, while preliminary results of another large, phase III trial, suggest that the combination of ranpirnase and doxorubicin could be more effective than doxorubicin alone. In all the above studies, ranpirnase seems to act mainly as a cytostatic rather than a cytotoxic drug, stabilizing progressive disease and potentially prolonging patients' survival. Ranpirnase may thus find its niche in combination with doxorubicin for mesothelioma as a second-line therapy, where no standard of care presently exists.
A Universal Part-of-Speech Tagset (2011)

To facilitate future research in unsupervised induction of syntactic structure and to standardize best-practices, we propose a tagset that consists of twelve universal part-of-speech categories. In addition to the tagset, we develop a mapping from 25 different treebank tagsets to this universal set. As a result, when combined with the original treebank data, this universal tagset and mapping produce a dataset consisting of common parts-of-speech for 22 different languages. We highlight the use of this resource via two experiments, including one that reports competitive accuracies for unsupervised grammar induction without gold standard part-of-speech tags.
Atrial Natriuretic Peptide Frameshift Mutation in Familial Atrial Fibrillation (2008)

Atrial fibrillation is a common arrhythmia that is hereditary in a small subgroup of patients. In a family with 11 clinically affected members, we mapped an atrial fibrillation locus to chromosome 1p36-p35 and identified a heterozygous frameshift mutation in the gene encoding atrial natriuretic peptide. Circulating chimeric atrial natriuretic peptide (ANP) was detected in high concentration in subjects with the mutation, and shortened atrial action potentials were seen in an isolated heart model, creating a possible substrate for atrial fibrillation. This report implicates perturbation of the atrial natriuretic peptide-cyclic guanosine monophosphate (cGMP) pathway in cardiac electrical instability.
Linker-Assisted Assembly and Interfacial Electron-Transfer Reactivity of Quantum Dot−Substrate Architectures (2010)

Bifunctional molecules can be used to tether quantum dots to nanostructured and planar semiconductor and metal surfaces. Excited-state interfacial electron-transfer reactions at QD−molecule−substrate interfaces are of interest from a fundamental standpoint and may have applications in solar energy conversion and charge-transfer-based sensing. This Perspective highlights recent work and unanswered questions in two related areas, the linker-assisted assembly of QD−substrate architectures and the spectroscopic characterization of electron transfer at QD−molecule−substrate interfaces.
Collapsin-1 Covalently Dimerizes, and Dimerization Is Necessary for Collapsing Activity (1998)

Chick collapsin-1, the first identified vertebrate member of the semaphorin family of axon guidance proteins, repels specific growth cones. Like all family members, collapsin-1 contains within its sequence a semaphorin domain that is necessary for specifying activity. Two additional structural domains of collapsin-1, the immunoglobulin (Ig) domain and the basic tail, each potentiate collapsin-1 activity. We identify in this study another structural feature of collapsin-1 that is necessary for its function. Collapsin-1 covalently dimerizes, and dimerization is necessary for collapse activity. This dimerization is mediated through a cysteine at residue 723, between the Ig domain and basic tail. The semaphorin domain alone is not active since it cannot dimerize. The collapsing activity of the semaphorin domain can be reconstituted when made as a chimeric construct with an immunoglobin Fc domain, which promotes dimerization.
Progress on new vaccine strategies against chronic viral infections (2004)

Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been sufficient for the vaccine to mimic the natural virus. However, viruses causing chronic infection do not elicit an immune response sufficient to clear the infection and, as a result, vaccines for these viruses must elicit more effective responses--quantitative and qualitative--than does the natural virus. Here we examine the immunologic and virologic basis for vaccines against three such viruses, HIV, hepatitis C virus, and human papillomavirus, and review progress in clinical trials to date. We also explore novel strategies for increasing the immunogenicity and efficacy of vaccines.
Crystal Structures of Monodisperse Colloidal Silica in Poly(methyl acrylate) Films (1997)

Dispersions of 22.3 vol % of 153 nm diameter silica particles coated with 3-(trimethoxysilyl)propyl methacrylate in liquid methyl acrylate (MA) as 264−528 μm thick films in glass cells spontaneously order into colloidal crystals and Bragg diffract visible light from lattice planes parallel to the film plane. Photopolymerization of the MA gives elastomeric poly(methyl acrylate) (PMA) films with retention of the crystalline order. Swelling the films with more MA and further polymerization give colloidal crystalline composite films with larger lattice spacings. The crystal structures are modeled as face centered cubic for the monomer dispersions and rhombohedral for the polymer films. Layer spacings observed in scanning electron micrographs (SEM) of microtomed PMA films are used to calculate the (111) spacings and the lattice parameter a of the model. The layer spacings correlate well with the diffraction wavelengths from optical spectra. Ultrasmall angle X-ray diffraction also was performed to demonstrate the three-dimensional crystalline order. The SEM and optical spectra also fit hexagonal close packed (hcp) or mixed rhombohedral and hcp structures.
Malleable and Self-Healing Covalent Polymer Networks through Tunable Dynamic Boronic Ester Bonds (2015)

Despite numerous strategies involving dynamic covalent bond exchange for dynamic and self-healing materials, it remains a challenge to be able to tune the malleability and self-healing properties of bulk materials through simple small molecule perturbations. Here we describe the use of tunable rates of boronic ester transesterification to tune the malleability and self-healing efficiencies of bulk materials. Specifically, we used two telechelic diboronic ester small molecules with variable transesterification kinetics to dynamically cross-link 1,2-diol-containing polymer backbones. The sample cross-linked with fast-exchanging diboronic ester showed enhanced malleability and accelerated healing compared to the slow-exchanging variant under the same conditions. Our report demonstrates the possibility of transferring small molecule kinetics to dynamic properties of bulk solid material and may serve as a guide for the rational design of tunable dynamic materials.
4．Protection of Patients and Human Subjects from Adverse Drug Reactions (2017)

して知られていた物が多い．ジギタリス(Digitalis purpurea)の毒は強心薬となり
The Nitration of 5-Methyl-2-thenoic Acid1 (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Nitration of 5-Methyl-2-thenoic Acid1E. Campaigne and Herschel G. GroseCite this: J. Am. Chem. Soc. 1951, 73, 8, 3812–3814Publication Date (Print):August 1, 1951Publication History Published online1 May 2002Published inissue 1 August 1951https://pubs.acs.org/doi/10.1021/ja01152a073https://doi.org/10.1021/ja01152a073research-articleACS PublicationsRequest reuse permissionsArticle Views85Altmetric-Citations10LEARN 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
Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment (2016)

Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects drug-metabolizing enzymes and drug transporters. These modifications influence the plasma concentration of substrates of drugs metabolized/transported by these enzymes. The direct-acting antivirals (DAAs) are substrates of, for example, cytochrome P450 enzymes in the liver. Most DAAs are not studied in HCV-infected individuals with decompensated cirrhosis, and therefore awareness is needed when these patients are treated. Most DAAs are contraindicated in cirrhotic patients; however, patients with a Child-Pugh score of B or C can be treated safely with a normal dose sofosbuvir plus ledipasvir or daclatasvir, in combination with ribavirin. Patients with renal impairment (glomerular filtration rate [GFR] <90 mL/min) or who are dependent on dialysis often tolerate ribavirin treatment poorly, even after dose adjustments. However, most DAAs can be used at the normal dose because DAAs are not renally excreted. To date, grazoprevir plus elbasvir is the preferred DAA regimen in patients with renal impairment as data are pending for sofosbuvir patients with GFR <30 mL/min (as for ledipasvir and velpatasvir). However, sofosbuvir has been used in a small number of patients with severe renal impairment and, based on these trials, we recommend sofosbuvir 400 mg every day when no other DAA regimen is available. Ledipasvir and velpatasvir are not recommended in patients with severe renal impairment.
Adsorption of Anaphylatoxins and Platelet-Specific Proteins by Filtration of Platelet Concentrates with a Polyester Leukocyte Reduction Filter (1994)

Anaphylatoxins generated during storage of platelet concentrates (PCs) may potentially have side effects on platelet transfusion. We evaluated the anaphy- latoxin-scavenging abilities of white blood cell reduction filters. Among the commercially available filters for PCs, one made with polyester fiber (PL50) dramatically adsorbed C3a and C4a anaphylatoxins to the respective mean level of 1,721-208 ng/ml and 1,240-141 ng/ml in 3-day-old PCs. C3a and C4a were measured as the native and des Arg form of each complement by radioimmunoassay. C3a and C4a anaphylatoxins in the supernatant plasma fraction from 3-day-old PC again decreased from 1,136 to 114 ng/ml and from 1,086 to 65 ng/ml, respectively. The filter also adsorbed 85% of platelet factor 4 (PF4) and 31% of β-thromboglobulin (β-TG), which had been released from platelets into the plasma during storage. The plasma levels of adhesive proteins such as fibronectin, fibrinogen, and von Willebrand factor, and plasma lactate dehydrogenase activity did not decrease after filtration. Another polyester filter (PL5A), on the other hand, significantly increased C3a and C4a levels with filtration. In addition, there was no PF4 adsorption ability during the filtration. The filters for red cells (RC50, BPF4, and R500A) had no anaphyla- toxin adsorption capabilities. The observed specific adsorption of anaphylatoxins might be attributed to the electrostatic force between the positively charged anaphylatoxins with high pi and the possibly negatively charged filter membranes. Since PF4 and ß-TG have positively charged moieties in the C-terminal position, the same adsorption mechanism might operate. We have obtained a useful scavenging filter for the evaluation of side effects of anaphylatoxins on patients who received old PCs.
Role of the vitamin D receptor in FGF23 action on phosphate metabolism (2005)

FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(-/-) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(-/-) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1a-hydroxylase mRNA levels in VDR(-/-) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(-/-) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.
Expression in High Yield of Pig α1β1 Na,K-ATPase and Inactive Mutants D369N and D807N in Saccharomyces cerevisiae (1996)

Studies of structure-function relationships in Na,K-ATPase require high yield expression of inactive mutations in cells without endogenous Na,K-ATPase activity. In this work we developed a host/vector system for expression of fully active pig Na,K-ATPase as well as the inactive mutations D369N and D807N at high levels in Saccharomyces cerevisiae. The alpha 1- and beta 1-subunit cDNAs were inserted into a single 2-microns-based plasmid with a high and regulatable copy number and strong galactose-inducible promoters allowing for stoichiometric alterations of gene dosage. The protease-deficient host strain was engineered to express high levels of GAL4 transactivating protein, thereby causing a 10-fold increase in expression to 32,500 +/- 3,000 [3H]ouabain sites/cell. In one bioreactor run 150-200 g of yeast were produced with 54 +/- 5 micrograms of Na,K-pump protein/g of cells. Through purification in membrane bound form the activity of the recombinant Na,K-ATPase was increased to 42-50 pmol/mg of protein. The Na,K dependence of ATP hydrolysis and the molar activity (4,500-7,000 min-1) were close to those of native pig kidney Na,K-ATPase. Mutations to the phosphorylation site (D369N) or presumptive cation sites (D807N), both devoid of Na,K-ATPase activity, were expressed in the yeast membrane at the same alpha-subunit concentration and [3H]ouabain binding capacity as the wild type Na,K-ATPase. The high yield and absence of endogenous activity allowed assay of [3H]ATP binding at equilibrium, demonstrating a remarkable 18-fold increase in affinity for ATP in consequence of reducing the negative charge at the phosphorylation site (D369N).
Mutants of Paracoccus denitrificans Deficient in c-type Cytochromes (1979)

Eight mutants of Paracoccus denitrificans deficient in c-type cytochrome were detected by their inability to catalyse the conversion of α-naphthol plus dimethyl-p-phenylenediamine to indophenol. From the properties of two of these mutants which completely lacked spectrophotometrically detectable c-type cytochrome, evidence was provided for the presence of a respiratory pathway which terminates in a cytochrome o-like oxidase. The presence of this pathway allows mutants lacking c-type cytochrome to grow aerobically, and also explains many of the non-mitochondrial features of the aerobic respiratory chain of the wild-type. None of the mutants had significantly lower levels of b-type cytochromes compared with the parental strain, but two mutants were deficient in cytochrome aa 3. All of the mutants could reduce nitrate, but four of them were unable to denitrify and these showed poor growth with nitrate as added terminal electron acceptor.