gebhart/patrepeval huggingface dataset:
Single‐Dose and Steady‐State Pharmacokinetics of Fentanyl Buccal Tablet in Healthy Volunteers (2006)

This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.
Annotating the human genome with Disease Ontology (2009)

The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome.
γ-secretase modulators: hopes and setbacks for the future of Alzheimer’s treatment (2008)

Alzheimer’s disease (AD) is the major cause of dementia and a debilitating ill-ness that affects a large proportion of the aged population, yet no effective treat-ment exists that could halt or reverse its progression. Therapeutic strategies are currently being developed that are aimed at controlling the levels of Aβ amyloid in the brain. Indeed, compelling genetic and experimental evidence indicate that accu-mulation of Aβ amyloid peptide is directly linked to the etiology of the disease
Differentiation of embryonic stem cells towards pancreatic progenitor cells and their transplantation into streptozotocin‐induced diabetic mice (2008)

Type I diabetes is characterized by the deficiency of endocrine beta cells in the pancreatic islets of Langerhans and transplantation of islet cells can be an effective therapeutic approach. Embryonic stem cells can be differentiated into any cell type, and therefore represent an unlimited source of islet cells for the transplantation and treatment for type I diabetes. We have adopted an easy and reproducible in vitro differentiation system with a reduced serum concentration plus nicotinamide to generate early pancreatic progenitor cells from embryonic stem cells. Gene expression analysis indicated that the differentiated cells expressed not only endoderm markers such as GATA-4, HNF-3beta, but also early markers of pancreatic development including key transcription factors PDX-1 and IAPP. Some pancreatic specific markers, such as insulin I, insulin II, Glu-2 and glucagon, were also expressed to some extent at the mRNA level. Differentiated ES cells showed low level immunoreactivity for insulin. However, transplantation of these early pancreatic progenitor clusters into STZ-induced diabetic mice failed to reverse the hyperglycemic state of the disease as reported previously. The results suggest that culture manipulation can direct ES cells to differentiate into early pancreatic progenitor cells committing to pancreatic islet cell fate, but these cells cannot function normally to reduce blood glucose of diabetic mice at this stage.
Intramolecular hydrophobic association of two alkyl chains of oligoethylene glycol diethers and diesters in water (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular hydrophobic association of two alkyl chains of oligoethylene glycol diethers and diesters in waterN. Funasaki, S. Hada, S. Neya, and K. MachidaCite this: J. Phys. Chem. 1984, 88, 24, 5786–5790Publication Date (Print):November 1, 1984Publication History Published online1 May 2002Published inissue 1 November 1984https://pubs.acs.org/doi/10.1021/j150668a009https://doi.org/10.1021/j150668a009research-articleACS PublicationsRequest reuse permissionsArticle Views111Altmetric-Citations24LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
PREVENTION OF DE NOVO HEPATITIS B INFECTION IN RECIPIENTS OF HEPATIC ALLOGRAFTS FROM ANTI-HBc POSITIVE DONORS (1999)

Combination therapy with HBIG and lamivudine may prevent de novo HBV infection in anti-HBs-, HbsAg- recipients of hepatic allografts from anti-HBc+ donors.
Biomineralisations in crustaceans: storage strategies (2004)

Les crustacés possèdent une remarquable aptitude à élaborer de manière cyclique deux types de calcification : un squelette externe (ou cuticule) inextensible, mais également, chez de nombreuses espèces, en fonction de leur mode de vie, des dépôts transitoires de calcium. Ils sont ainsi sujets à une balance calcique se produisant périodiquement entre deux sources de calcium, exogène et/ou endogène. Les structures de stockage, constituées en majorité de carbonate de calcium précipité au sein d&rsquo;une matrice organique essentiellement protéique, sont très diversifiées. Alors que le carbonate de calcium se présente sous une forme essentiellement cristalline (pouvant coexister avec la forme amorphe) au niveau cuticulaire chez la plupart des espèces, il adopte une forme exclusivement amorphe au niveau des dépôts calciques. C&rsquo;est la matrice organique qui est responsable du polymorphe et de la morphologie de la biominéralisation. C&rsquo;est pourquoi la caractérisation des constituants des matrices organiques constitue un préalable à la compréhension de la formation des structures calcifiées : à ce jour, seules quelques protéines matricielles sont bien caractérisées chez les crustacés. Un autre intérêt des crustacés repose sur la présence d&rsquo;épithéliums calcifiants (mais aussi décalcifiants), élaborant (et résorbant) les structures de stockage calcique, et dont l&rsquo;étude permet de mieux comprendre le fonctionnement des tissus similaires rencontrés chez les vertébrés. De même, les crustacés constituent d&rsquo;excellents modèles pour la compréhension de la régulation hormonale des systèmes calcifiants, d&rsquo;autant qu&rsquo;en plus d&rsquo;un rôle probable de certains ecdystéroïdes, la trilogie hormonale contrôlant le métabolisme calcique des vertébrés (CT/PTH/Vit. D) pourrait être également fonctionnelle chez les crustacés.
Characterization of the maize gene sugary1, a determinant of starch composition in kernels. (1995)

In maize kernels, mutations in the gene sugary1 (su1) result in (1) increased sucrose concentration; (2) decreased concentration of amylopectin, the branched component of starch; and (3) accumulation of the highly branched glucopolysaccharide phytoglycogen. To investigate further the mechanisms of storage carbohydrate synthesis in maize, part of the su1 gene locus and a cDNA copy of the su1 transcript were characterized. Five new su1 mutations were isolated in a Mutator background, and the mutant allele su1-R4582::Mu1 was isolated by transposon tagging. The identity of the cloned element as the su1 gene locus was confirmed by the cosegregation of restriction fragment length polymorphisms in the same or nearby genomic intervals with three additional, independent su1 mutations. Pedigree analysis was also used to confirm the identity of su1. A 2.8-kb mRNA that is homologous to the cloned gene was detected in maize kernels, and a 2.7-kb cDNA clone was isolated based on hybridization to the genomic DNA. Specific portions of the cDNA hybridized with multiple segments of the maize genome, suggesting that su1 is part of a multigene family. The cDNA sequence specified a polypeptide of at least 742 amino acids, which is highly similar in amino acid sequence to bacterial enzymes that hydrolyze alpha-(1-->6) glucosyl linkages of starch. Therefore, debranching of glucopolysaccharides is seemingly part of the normal process of starch biosynthesis, and the final degree of branch linkages in starch most likely arises from the combined actions of branching and debranching enzymes.
pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants (2009)

Agro-infiltration of leaf tissue with binary vectors harbouring a sequence of interest is a rapid method of expressing proteins in plants. It has recently been shown that flanking the sequence to be expressed with a modified 5'-untranslated region (UTR) and the 3'-UTR from Cowpea mosaic virus (CPMV) RNA-2 (CPMV-HT) within the binary vector pBINPLUS greatly enhances the level of expression that can be achieved [Sainsbury, F. and Lomonossoff, G.P. (2008)Plant Physiol. 148, 1212-1218]. To exploit this finding, a series of small binary vectors tailored for transient expression (termed the pEAQ vectors) has been created. In these, more than 7 kb of non-essential sequence was removed from the pBINPLUS backbone and T-DNA region, and unique restriction sites were introduced to allow for accommodation of multiple expression cassettes, including that for a suppressor of silencing, on the same plasmid. These vectors allow the high-level simultaneous expression of multiple polypeptides from a single plasmid within a few days. Furthermore, vectors have been developed which allow the direct cloning of genes into the binary plasmid by both restriction enzyme-based cloning and GATEWAY recombination. In both cases, N- or C-terminal histidine tags may be fused to the target sequence as required. These vectors provide an easy and quick tool for the production of milligram quantities of recombinant proteins from plants with standard plant research techniques at a bench-top scale.
Fertilization and early embryology: The influence of Vero cell culture on human embryo development and chorionic gonadotrophin production in vitro (1996)

Co-culture of human embryos with cell layers has generally shown that blastocyst formation rates are improved compared to routine culture in medium alone. In order to assess this further, we have additionally classified resulting blastocysts according to their morphology and secretion of human chorionic gonadotrophin (HCG). A total of 70 supernumerary human embryos from 15 patients were divided equally and randomly between two culture conditions: (i) co-culture with Vero cells; and (ii) culture in our routine medium. Embryo development and morphology were recorded for up to 14 days in culture. The results showed that embryos on Vero cells had a significantly higher blastocyst formation rate (P < 0.02) by or on day 6 of development than those in routine culture medium alone (77 and 46% respectively). For HCG analysis, the culture medium was changed in both culture systems on days 5, 7, 9, 12 and 14 of embryo development and analysed. Most embryos began to produce HCG between days 7 and 9, with HCG secretion being significantly higher from embryos on Vero cells between days 9 and 12 than from embryos in routine culture (P < 0.03). The morphology of the blastocysts obtained was related to their ability to hatch and produce HCG but was not significantly better for one type of culture system than for the other.
The Multi-Relational Skyline Operator (2007)

Most of the existing work on skyline query has been extensively used in decision support, recommending systems etc, and mainly focuses on the efficiency issue for a single table. However the data retrieved by users for the targeting skylines may often be stored in multiple tables, thus require to perform join operations among tables. As a result, the cost on computing skylines on the joined table will be increased dramatically due to its potentially increasing cardinality and dimensionality. In this paper, we systematically study the skyline operator on multi-relational databases, and propose solutions aiming to seamlessly integrating state-of-the-art join methods into skyline computation. Our experiments not only demonstrate that the proposed methods are efficient, but also show the promising applicability of extending skyline operator to other typical database operators such as join and aggregates.
CD30/CD30 Ligand and CD40/CD40 Ligand in Malignant Lymphoid Disorders (1999)

CD30 and CD40 are members of the tumor necrosis factor (TNF) receptor family. These two receptors have pleiotropic biologic functions including induction of apoptosis and enhancing cell survival. This review will discuss the pattern of expression of these receptors in malignant lymphoid disorders and their prospective ligands. Understanding issues related to these two ligands and their receptors in lymphoid malignancies may help to improve the classification of these diseases and could open the doors for new treatment strategies.
A mechanistic model of tau amyloid aggregation based on direct observation of oligomers (2015)

Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.
A Skin Cancer Virus? (2008)

High-throughput DNA sequencing has identified a new human virus in a rare but aggressive form of skin cancer.
Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines (2003)

The self-renewal and differentiation of hematopoietic progenitors are regulated by the interaction between Notch receptors and Notch ligands. Since AML originates from dysregulated hematopoietic progenitors, some abnormalities in the Notch system may be involved in the abnormal proliferation of AML cells. However, the significance of the Notch system in AML is not known. We examined the functional roles of Notch activation on the in vitro growth of seven human AML cell lines using three kinds of recombinant Notch ligand proteins, Jagged-1, Delta-1 and Delta-4. The ligands significantly affected the growth of two cell lines. In TMD7 cells, Delta proteins promoted the short-term growth, however, suppressing the self-renewal capacity and long-term growth. In OCI/AML-6 cells, Delta proteins suppressed the growth and self-renewal capacity while inducing differentiation into macrophage-like cells. We additionally found that Notch ligands needed to be immobilized on culture wells to affect the cells. These findings were in contrast to our hypothesis that Notch activation in AML cells leads to excessive self-renewal capacity and proliferation. If the Notch system in AML cells is precisely understood, the control of Notch activation will become a novel therapeutic approach for AML.
Post-transcriptional regulation of gene expression in response to iron deficiency: co-ordinated metabolic reprogramming by yeast mRNA-binding proteins (2008)

Saccharomyces cerevisiae (baker's yeast) is an excellent model for understanding fundamental biological mechanisms that are conserved in Nature and that have an impact on human disease. The metal iron is a redox-active cofactor that plays critical biochemical roles in a broad range of functions, including oxygen transport, mitochondrial oxidative phosphorylation, chromatin remodelling, intermediary metabolism and signalling. Although iron deficiency is the most common nutritional disorder on the planet, little is known about the metabolic adjustments that cells undergo in response to iron deficit and the regulatory mechanisms that allow these adaptive responses. In the present article, we summarize recent work on genome-wide metabolic reprogramming in response to iron deficiency, mediated by specific mRNA degradation mechanisms that allow S. cerevisiae cells to adapt to iron deficiency.
Whole genome microarray analysis in non-small cell lung cancer (2015)

Lung cancer is a serious health problem, since it is one of the leading causes for death worldwide. Molecular-cytogenetic studies could provide reliable data about genetic alterations which could be related to disease pathogenesis and be used for better prognosis and treatment strategies. We performed whole genome oligonucleotide microarray-based comparative genomic hybridization in 10 samples of non-small cell lung cancer. Trisomies were discovered for chromosomes 1, 13, 18 and 20. Chromosome arms 5p, 7p, 11q, 20q and Хq were affected by genetic gains, and 1p, 5q, 10q and 15q, by genetic losses. Microstructural (<5 Mbp) genomic aberrations were revealed: gains in regions 7p (containing the epidermal growth factor receptor gene) and 12p (containing <i>KRAS</i>) and losses in 3p26 and 4q34. Based on high amplitude of alterations and small overlapping regions, new potential oncogenes may be suggested: <i>NBPF4</i> (1p13.3); <i>ETV1</i>, <i>AGR3</i> and <i>TSPAN13</i> (7p21.3-7p21.1); <i>SOX5</i> and <i>FGFR1OP2</i> (12p12.1-12p11.22); <i>GPC6</i> (13q32.1). Significant genetic losses were assumed to contain potential tumour-suppressor genes: <i>DPYD</i> (1p21.3); <i>CLDN22</i>, <i>CLDN24</i>, <i>ING2</i>, <i>CASP3</i>, <i>SORBS2</i> (4q34.2-q35.1); <i>DEFB</i> (8p23.1). Our results complement the picture of genomic characterization of non-small cell lung cancer.
In Vitro and In Vivo Effect of HPMA Copolymer-bound Doxorubicin Targeted to Transferrin Receptor of B-cell Lymphoma 38C13 (2002)

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing the anticancer agent doxorubicin and targeted to the transferrin receptor either with anti-mouse CD71 monoclonal antibody (mAb) or with transferrin were synthesized to evaluate their binding and anti-proliferative activity in vitro and anti-tumor potential against 38C13 B-cell lymphoma in vivo. Both the doxorubicin and the targeting moieties were bound to HPMA copolymer chain by aminolysis via a Gly-Phe(D,L)-Leu-Gly spacer to ensure controlled intracellular release of the conjugated drug. We demonstrated that HPMA copolymer-bound doxorubicin targeted to the transferrin receptor with anti-mouse CD71 mAb strongly retards tumor growth, prolongs the survival and completely cures three out of nine experimental mice with established 38C13 tumors. The conjugate targeted with transferrin was less effective in vitro as well as in vivo. It completely cured only one out of seven experimental mice. Free or non-targeted HPMA copolymer-bound doxorubicin showed only a mild anti-tumor effect within the therapeutic schedule used. In vitro, HPMA copolymer-bound doxorubicin targeted with anti-mouse CD71 mAb shows approximately 4-fold higher cytotoxic effect than HPMA copolymer-bound doxorubicin targeted with transferin and 9-fold higher cytotoxic effect than non-targeted HPMA copolymer-bound doxorubicin.
NMR Studies of Substrate Binding to Cytochrome P450 BM3: Comparisons to Cytochrome P450 cam (1995)

The binding of the substrates sodium laurate and sodium 12-bromolaurate to the heme-containing domain of Bacillus megaterium cytochrome P450 BM3 (CYP102) has been studied by measurement of the relaxation effects of the unpaired electrons of the heme iron on the protons of water and of the bound substrates. Substrate binding leads to a conversion of the heme iron from a low-spin to a high-spin state, as shown by changes in the optical spectrum. The relaxation measurements show that this is accompanied by expulsion of water from the sixth coordination position of the iron, the distance between the iron and the water protons increasing from 2.6 to 5.2 A. Corresponding relaxation measurements on the substrate protons lead to the determination of a number of distances between the iron and protons of the bound substrate and, hence, to information on the position and orientation of the substrate in the binding site. Laurate and 12-bromolaurate are found to bind in a very similar way, in an extended conformation with the carboxylate probably close to Arg47 and the other end of the chain 7.6-7.8 A from the heme iron. It is shown that laurate and pyridine can bind simultaneously to the P450 domain and that the iron-laurate distances in this ternary complex are not significantly different from those in the binary complex. These observations are compared with those on the substrate complex of cytochrome P450 cam, and their implications for structural changes involved in the catalytic cycle are discussed.
An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma (2014)

High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive form of epithelial ovarian cancer, for which few targeted therapies exist. To search for new therapeutic target proteins, we performed an in vivo shRNA screen using an established human HGSOC cell line growing either subcutaneously or intraperitoneally in immunocompromised mice. We identified genes previously implicated in ovarian cancer such as AURKA1, ERBB3, CDK2, and mTOR, as well as several novel candidates including BRD4, VRK1, and GALK2. We confirmed, using both genetic and pharmacologic approaches, that the activity of BRD4, an epigenetic transcription modulator, is necessary for proliferation/survival of both an established human ovarian cancer cell line (OVCAR8) and a subset of primary serous ovarian cancer cell strains (DFs). Among the DFs tested, the strains sensitive to BRD4 inhibition revealed elevated expression of either MYCN or c-MYC, with MYCN expression correlating closely with JQ1 sensitivity. Accordingly, primary human xenografts derived from high-MYCN or c-MYC strains exhibited sensitivity to BRD4 inhibition. These data suggest that BRD4 inhibition represents a new therapeutic approach for MYC-overexpressing HGSOCs.