gebhart/patrepeval huggingface dataset:
Discovery of Potent and Highly Selective Inhibitors of GSK3b (2014)

The serine/threonine kinase glycogen synthase kinase-3 beta (GSK3b) is a known master regulator for several cellular pathways that include insulin signaling and glycogen synthesis, neurotrophic factor signaling, Wnt signaling, neurotransmitter signaling and microtubule dynamics. Consequently, this enzyme has been implicated in multiple human disorders including Alzheimer’s disease, bipolar disorder, noninsulin-dependent diabetes mellitus, cardiac hypertrophy, and cancer. Precisely how GSK3b maintains its pathway specificity efficiently at the crossroads of many cellular processes is still unclear. Many inhibitors of GSK3b exist, however these compounds have been found lacking in selectivity, with CHIR 99021 considered most potent and selective. The goal for this project is to identify potent and highly selective small molecule probes to investigate GSK3b biology in cellular and ultimately in whole animal models. A library of over three hundred twenty thousand compounds was screened against human GSK3b. Among the inhibitors identified, CID 5706819 showed decent potency and excellent selectivity inhibiting only five out of over three hundred kinases at 10 μM by over fifty percent. Subsequent chemical modifications of CID 5706819, guided by a co-crystal structure with GSK3b, and a battery of biochemical and cell-based assays led to CID 56840716/ML320 that inhibits GSK3b at IC50 between 10–30 nM. ML320 has a superior kinome-wide selectivity profile compared to CHIR99021. Further, ML320 demonstrates excellent cellular activity in inhibiting GSK3b-mediated Tau phosphorylation in SH-SY5Y neuroblastoma cells (IC50 of 1 μM), and in relieving negative regulation by GSK3b on cellular beta-catenin degradation and TCF/LEF promoter activities with EC50 of 5 μM in both assays. At the same time, no cellular toxicity by ML320 was observed in SH-SY5Y cells at the highest testing concentration of 30 μM. Taken together, ML320 is a potent and highly selective small molecular probe against GSK3b, allowing better investigation and interpretation of GSK3b cellular functions than the existing prior art. ML320 scaffold also holds the promise to deliver additional compounds with further improved biochemical, cellular, and pharmacokinetic properties suitable for investigating in vivo roles of GSK3b in pertinent animal physiology and pathology.
Resistance of hyaluronate coatings to hyaluronidase (1994)

Mucopolysaccharides such as hyaluronic acid and its salts are essential components of new hydrophilic bilaminar coatings being developed in these laboratories. The polysaccharide top-coat is covalently bonded by periodic urethane links to a substrate copolymer which in this study has been coated on polymethyl methacrylate slabs. Such coated slabs were exposed for up to 28 months to three levels of hyaluronidase in phosphate buffered saline at 37 degrees C, the enzyme concentration ranging from that normally present in human serum to 60 times that level. The coating survived without damage. The rationale proposed is that the enzyme is unable to position its active site with the immobilized hyaluronate molecule and is therefore unable to catalyze the hydrolysis.
“p-on-n” Si interband tunnel diode grown by molecular beam epitaxy (2001)

Si interband tunnel diodes have been successfully fabricated by molecular beam epitaxy and room temperature peak-to-valley current ratios of 1.7 have been achieved. The diodes consist of opposing n- and p-type δ-doped injectors separated by an intrinsic Si spacer. A “p-on-n” configuration was achieved for the first time using a novel low temperature growth technique that exploits the strong surface segregation behavior of Sb, the n-type dopant, to produce sharp delta-doped profiles adjacent to the intrinsic Si spacer.
Intravenous infusion of total dose iron is superior to oral iron in treatment of anemia in peritoneal dialysis patients (1998)

In the treatment of anemia of chronic renal failure, the most common cause of recombinant human erythropoietin (rhEPO) resistance is iron deficiency. In peritoneal dialysis (PD) patients, oral iron therapy is an accepted and convenient method of iron supplementation. The effectiveness of oral iron, however, is limited by many factors, including gastrointestinal side effects and poor gastric absorption. This study prospectively compared the efficacy of single intravenous infusion of total dose iron (ITDI group) given in an outpatient setting with oral iron (oral group) for the treatment of anemia in PD patients. Twenty-five adult stable PD patients with baseline hematocrit 25 to 35% were entered into the study. Thirteen patients with serum transferrin saturation (TSAT) < 25% received ITDI, and 12 patients with TSAT between 25 and 35% received oral iron. One patient in the oral group received emergent blood transfusion and was excluded from analysis. Hematocrit and iron indices were measured at monthly intervals. Doses of rhEPO were adjusted monthly to maintain target hematocrit at 35%. At the end of the study (6 mo), despite similar baseline mean hematocrit (31.0 +/- 0.9 versus 33.0 +/- 1.0%), comparable mean baseline weekly rhEPO dose (7886 +/- 1449 versus 6370 +/- 1553 U/wk), and significantly lower level of mean TSAT (11.3 +/- 3.5 versus 30.1 +/- 3.5%; P < 0.05), the ITDI group when compared with the oral group had significantly higher mean hematocrit (36.0 +/- 1.0 versus 31.4 +/- 1.1%; P < 0.05) and TSAT (33.7 +/- 3.7 versus 22.6 +/- 4.0%; P < 0.05) values. In addition, the final mean dose of weekly rhEPO was significantly lower in the ITDI group (4799 +/- 981 versus 9998 +/- 1027 U/wk; P < 0.05). No patient in the ITDI group developed an adverse reaction to intravenous iron. It is concluded that ITDI represents a more efficacious method of iron supplementation in PD patients receiving rhEPO. Moreover, ITDI is safe and well tolerated and can be administered in an outpatient setting.
CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer (2004)

Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis.
Information access for visually impaired persons: do we still keep a "document" in "documentation"? (2002)

At the same time that global economies and multimedia technologies provide impetus for increasingly visual communication, the information needs of persons with limited vision may require communication to shift from graphics back to text, or on to audio or tactile forms. To understand documentation issues related to this shift, one must understand the varied forms of visual impairment, available assistive technologies, and the resultant design considerations. Efforts to prepare more effective materials for visually impaired users may yield "universal design" benefits by identifying and reducing sources of confusion for all users.
Cystic Fibrosis Transmembrane Conductance Regulator Differentially Regulates Human and Mouse Epithelial Sodium Channels in Xenopus Oocytes (2004)

The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl- channel properties, regulates other ion channels. CFTR inhibits murine or rat epithelial Na+ channel (mENaC or rENaC) currents in many epithelial and non-epithelial cells, whereas murine or rat ENaC increases CFTR functional expression. These regulatory interactions are reproduced in Xenopus oocytes where both the open probability and surface expression of wild type CFTR Cl- channels are increased when CFTR is co-expressed with alphabetagamma mENaC, and conversely the activity of mENaC is inhibited after wild type CFTR activation. Using the Xenopus oocyte expression system, differences in functional regulatory interactions were observed when CFTR was co-expressed with either alphabetagamma mENaC or alphabetagamma human ENaC (hENaC). Co-expression of CFTR and alphabetagamma mENaC or hENaC resulted in an approximately 3-fold increase in CFTR Cl- current compared with oocytes expressing CFTR alone. Oocytes co-injected with both CFTR and mENaC or hENaC expressed an amiloride-sensitive whole cell current that was decreased compared with that observed with the injection of mENaC or hENaC alone before CFTR activation with forskolin/3-isobutyl-1-methylxanthine. CFTR activation resulted in a further 50% decrease in mENaC-mediated currents, an approximately 20% decrease in alpha-T663-hENaC-mediated currents, and essentially no change in alpha-A663-hENaC-mediated currents. Changes in ENaC functional expression correlated with ENaC surface expression by oocyte surface biotinylation experiments. Assessment of regulatory interactions between CFTR and chimeric mouse/human ENaCs suggest that the 20 C-terminal amino acid residues of alpha ENaC confer species specificity regarding ENaC inhibition by activated CFTR.
Self-Assembly of Block Copolymers on Lithographically Defined Nanopatterned Substrates (2007)

A review of the method, results, and possible benefits of the directed assembly of block copolymers on lithographically defined, chemically nanopatterned substrates. Insertion of block copolymers into the lithographic process showed the potential to reduce critical dimension variation in the lithographic process by correcting for process variations in the original lithographically defined pattern. The ability of directed assembly of block copolymers to yield a variety of device oriented patterns while maintaining registration to the substrate and a high degree of perfection was demonstrated. Directed assembly of block copolymers was also able to generate structures that do not naturally occur in the bulk, such as square arrays of cylindrical domains and quadratically perforated lamellae.
One-dimensional aromatic crystals in solution. 4. Ground- and excited-state interactions of poly(L-1-pyrenylalanine) studied by chiroptical spectroscopy including circularly polarized fluorescence and fluorescence-detected circular dichroism (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOne-dimensional aromatic crystals in solution. 4. Ground- and excited-state interactions of poly(L-1-pyrenylalanine) studied by chiroptical spectroscopy including circularly polarized fluorescence and fluorescence-detected circular dichroismSyun Egusa, Masahiko Sisido, and Yukio ImanishiCite this: Macromolecules 1985, 18, 5, 882–889Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ma00147a011https://doi.org/10.1021/ma00147a011research-articleACS PublicationsRequest reuse permissionsArticle Views233Altmetric-Citations55LEARN 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
Enzymes in organic syntheses. 19. Evaluation of the stereoselectivities of horse liver alcohol dehydrogenase; catalyzed oxidoreductions of hydroxy- and ketothiolanes, -thianes, and -thiepanes (1981)

The specificity of horse liver alcohol dehydrogenase (HLADH) with respect to unsubstituted five-, six-, and seven-membered ring 3- and 4-thiaketone and -thiaalcohol substrates has been examined. The enzyme is found to have a broad tolerance of the structural variations within this series. HLADH also exhibits encouraging (up to 46%) enantiotopic and enantiomeric specificity in preparative-scale reduction and oxidation reactions of the heterocyclic ketones and alcohols respectively.
Delay of supraspinatus repair by up to 12 weeks does not impair enthesis formation: A quantitative histologic study in rabbits (2005)

The purpose of this study was to find out whether supraspinatus repair delayed by up to12 weeks affects the formation of a new enthesis when compared to an immediate repair. In 67 rabbits, the supraspinatus fibrocartilaginous enthesis of one shoulder was resected. The tendon was attached to the greater tuberosity either immediately, after a 6-week, or after a 12-week delay. Five histologic variables were used to assess enthesis formation: number of non-chondrocytes, number of chondrocytes, alignment of chondrocytes in rows, area of metachromasia on toluidine blue (TB)-stained sections indicating proteoglycan content, and area of diffracted polarized light indicating spatial alignment of collagen fibers. For every variable, progressive enthesis formation was observed. Again, for every variable and at every time point studied, no statistically significant difference was observed between tendons repaired immediately, after 6, or after 12 weeks (all p>0.05). Supraspinatus tendon repairs delayed by 6 and 12 weeks constituted an enthesis which proceeded identically to one immediately repaired. Formation of a fibrocartilaginous enthesis depended on the elapsed time after repair and not on the duration between detachment and repair. Despite stated limitations, these results support both a trial of conservative treatment after a rotator cuff tear and a positive outcome of rotator cuff repair even if delayed by up to 12 weeks.
Small-sample estimation of negative binomial dispersion, with applications to SAGE data (2007)

We derive a quantile-adjusted conditional maximum likelihood estimator for the dispersion parameter of the negative binomial distribution and compare its performance, in terms of bias, to various other methods. Our estimation scheme outperforms all other methods in very small samples, typical of those from serial analysis of gene expression studies, the motivating data for this study. The impact of dispersion estimation on hypothesis testing is studied. We derive an "exact" test that outperforms the standard approximate asymptotic tests.
Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats. (1985)

Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues.
Rational design on n-type organic materials for high performance organic photovoltaics (2013)

The demand for further optimization of the photovoltaic efficiency has stimulated an intensive research effort both for new low-band-gap polymeric materials as electron donors and for new efficient electron-accepting materials. As regards the latter, less attention has been observed on the optimization of the electron acceptor material compared to the extensive studies on the electron donor polymer in organic photovoltaic (OPV) cells. The majority of the acceptor materials used so far in solar cells are organic (carbon based) materials, however other traditional acceptor materials include inorganic semiconductors, such as cadmium selenide (CdSe) nanocrystals, titanium oxide (TiO2) and zinc oxide (ZnO) nanoparticles. From the implemented organic materials high power conversion efficiencies PCEs (>9.0%) are observed in OPVs utilizing fullerene derivatives and especially [6,6]-phenyl-C61 butyric acid methyl ester (PC60BM) as the acceptor. Recently, very promising efficiencies of ∼5.0% have been also obtained by Polyera corporation utilizing soluble conjugated polymers as both the donor and the acceptor components. It is therefore expected that through improved materials design for enhancing the electron mobility, better tuning of the energy levels and absorption profile of organic materials, significant improvements in the device performance can still be expected. In this work, the current trends on the most promising solution processable n-type organic materials (fullerene derivatives, small molecules and conjugated polymers) will be presented in detail, emphasizing on the correlation between structure/optoelectronic properties/morphology characterization and device performances.
Differential Expression of Ribosomal Proteins in Human Normal and Neoplastic Colorectum (2003)

Ribosomal proteins are a major component of ribosomes and play critical roles in protein biosynthesis. Recently it has been shown that the ribosomal proteins also function during various cellular processes that are independent of protein biosynthesis therefore called extraribosomal functions. In this study we have, for the first time, determined the expression profile of 12 ribosomal proteins (Sa, S8, S11, S12, S18, S24, L7, L13a, L18, L28, L32, and L35a) in normal epithelia of human colorectal mucosa using immunohistochemistry (IHC) and then compared their expression patterns with those of colorectal cancer. In the normal mucosa, ribosomal proteins were largely associated with the ribosomes of mucosal epithelia, and the expression level of ribosomal proteins, except for S11 and L7 proteins, was markedly increased in associated with maturation of the mucosal cells. On the other hand, these ribosomal proteins were markedly decreased in colorectal cancer compared with the normal mucosa. By contrast, S11 and L7 ribosomal proteins were rarely associated with the ribosomes of colorectal epithilia except immature mucosal cells, whereas their expression levels were significantly enhanced in colorectal cancer cells. In addition, L7 ribosomal protein was detected in the secretory granules of the enterochromaffin cells in the colorectal mucosa and in carcinoma cells expressing chromogranin A. These results indicate that the expression of ribosomal proteins is differentially regulated not only in normal mucosa but also in carcinoma of human colorectum, and suggest an extraribosomal function of L7 ribosomal protein in neuroendocrine function.
Tellurium Dioxide Suspension in the Treatment of Seborrhea Capitis (1958)

Placed as they are within a family group in the periodic table, the four elements, oxygen, sulfur, selenium, and tellurium, are generally known to be related in their chemical properties.<sup>1</sup>Additionally, it has been demonstrated within recent years that sulfur and selenium<sup>2</sup>possess related therapeutic properties which are of particular value to the dermatologist in his treatment of seborrhea capitis. In consideration of the long history of sulfur as an effective agent in the treatment of dermatoses and of the proof through investigation of the value of selenium compounds,<sup>3</sup>it was deemed wise to assume that compounds of tellurium might have similar therapeutic application. During the past four years a standard 2.5% suspension of tellurium dioxide in a suitable shampoo vehicle has been used in intensive clinical studies. Safety tests<sup>4</sup>were carried out on laboratory animals, and excretion studies<sup>5</sup>on human urine were made