gebhart/patrepeval huggingface dataset:
Rat β-galactoside α2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts (1990)

The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.
Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure (2019)

URL: http://www.clinicaltrials.gov . Unique identifier: NCT01327846.
Nanopattern Formation from Tethered PS-b-PMMA Brushes upon Treatment with Selective Solvents (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNanopattern Formation from Tethered PS-b-PMMA Brushes upon Treatment with Selective SolventsBin Zhao, William J. Brittain, Wensheng Zhou, and Stephen Z. D. ChengView Author Information Department of Polymer Science The University of Akron, Akron, Ohio 44325-3909 Cite this: J. Am. Chem. Soc. 2000, 122, 10, 2407–2408Publication Date (Web):February 26, 2000Publication History Received13 July 1999Published online26 February 2000Published inissue 1 March 2000https://pubs.acs.org/doi/10.1021/ja992465zhttps://doi.org/10.1021/ja992465zrapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views2897Altmetric-Citations173LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Copolymers,Layers,Organic compounds,Solvents,Surface roughness Get e-Alerts
Validation of immunohistochemical quantification in confocal scanning laser microscopy: a comparative assessment of gap junction size with confocal and ultrastructural techniques. (1993)

Confocal scanning laser microscopy (CSLM) is increasingly being used to image antibody-labeled structures visualized with a fluorescent secondary antibody. Such digital images are routinely stored on computer and are well suited to quantitative analysis. Although theoretical aspects of CSLM imaging and resolution are well defined, information is lacking on the relationship observed between measurements of fluorescent antibody-labeled structures and the size of the same structures as determined by electron microscopy (EM). In the present study we examined this relationship for the cardiac gap junction. Data on the size of immunofluorescent-labeled gap junctions were acquired by two methods of analysis from CSLM images and compared statistically with measurements of gap junction size obtained by freeze-fracture EM. The freeze-fracture data were compared before and after exclusion of small junctions, corresponding to those that theoretically would not have been detected in CSLM analysis. The data obtained by the different methods were similar but not identical, reflecting the advantages and limitations of each technique. However, the comparison did indicate that with appropriate sample preparation and orientation, accurate and rapid analysis can be achieved by CSLM, particularly when digital semi-automated techniques are employed.
Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats. (1996)

Chronically elevated shear stress and inflammation are important in hypertensive lung vessel remodeling. We postulate that 5-lipoxygenase (5-LO) is a molecular determinant of these processes. Immunohistology localized the 5-LO to macrophages of normal and chronically hypoxic rat lungs and also to vascular endothelial cells in chronically hypoxic lungs only. In situ hybridization of normal and chronically hypoxic lungs demonstrated that 5-LO mRNA is expressed in macrophages. Rats hypoxic for 4 wk-developed pulmonary hypertension increased translocation of the lung 5-LO from the cytosol to the membrane fraction and increased levels of lung tissue 5-lipoxygenase-activating protein (FLAP). A FLAP ligand, 3-[l-(4-chlorobenzyl)-3-t-butyl-thio-t-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (MK-886), inhibited the acute angiotensin II and hypoxia-induced pulmonary vasoconstriction in vitro and the development of chronic hypoxic pulmonary hypertension in rats in vivo. Mice bred with the deletion of the 5-LO enzyme (5-LO knockout) developed less right heart hypertrophy than age-matched 5-LO competent mice. Our results support the hypothesis that the 5-LO is involved in lung vascular tone regulation and in the development of chronic pulmonary hypertension in hypoxic rodent models.
Polymeric Hydrogels: Characterization and Biomedical Applications (2009)

Hydrogels are cross-linked polymeric networks, which have the ability to hold water within the spaces available among the polymeric chains. The hydrogels have been used extensively in various biomedical applications, e.g., drug delivery, cell carriers and/or entrapment, wound management and tissue engineering. Though far from extensive, this article has been devoted to study the common methods used for the characterization of the hydrogels and to review the range of applications of the same in health care.
Regulatory B10 Cells Differentiate into Antibody-Secreting Cells After Transient IL-10 Production In Vivo (2011)

Regulatory B cells that are functionally defined by their capacity to express IL-10 (B10 cells) downregulate inflammation and autoimmunity. In studies using well-defined IL-10 reporter mice, this rare B10 cell subset was also found to maintain a capacity for plasma cell differentiation. During a transient period of il10 transcription, the blimp1 and irf4 transcription factors were induced in B10 cells, whereas pax5 and bcl6 were downregulated as a significant fraction of B10 cells completed the genetic and phenotypic program leading to Ab-secreting cell differentiation in vitro and in vivo. B10 cell-derived IgM reacted with both self- and foreign Ags, whereas B10 cells generated Ag-specific IgG in response to immunizations. Moreover, B10 cells represented a significant source of serum IgM and IgG during adoptive-transfer experiments and produced Ag-specific, polyreactive and autoreactive Ab specificities that were consistent with their expression of a diverse AgR repertoire. Thereby, B10 cells limit inflammation and immune responses by the transient production of IL-10, and may facilitate clearance of their eliciting Ags through an inherent capacity to quickly generate polyreactive and/or Ag-specific Abs during humoral immune responses.
Design, synthesis and antiinflammatory activity of a new indomethacin ester. 2-(N-(3-{3-(piperidinomethyl)phenoxy}propyl)carbamoylmethylthio)ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate. (1991)

A novel indomethacin ester prodrug, 2-[N-[3-(3-(piperidinomethyl)phenoxy)propyl]carbamoylmethylthio ]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate (1) was prepared from a new histamine H2-receptor antagonist, N-[3-(3-(piperidinomethyl)phenoxy)propyl]-2-(2-hydroxyethylthio )acetamide (2) and indomethacin (3). The compound 1 was shown to be essentially similar to 3 in its antiinflammatory action and to almost completely inhibit carrageenin-induced hind-paw edema in the rat at a very high dose of 230 mg/kg (280 mumol/kg), which is comparable to that of 100 mg/kg (280 mumol/kg) of 3, without producing gastric lesions. On a molar basis, the acute gastric lesioning properties of 1 were near one-hundred times less than those of 3, resulting in over a twenty-fold improvement in the ratio of antiedema activity to ulcerogenicity. The effect of the co-administration of histamine H2-receptor antagonists on antiedema activity and ulcerogenicity caused by 3 is also discussed.
Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice (1996)

Recently, the ligand for the Mpl receptor (ML) was identified to be thrombopoietin, the principal regulator of megakaryocytopoiesis and thrombopoiesis. We examined the effects of ML, as a single factor or in combinations with early acting factors such as steel factor (SF), interleukin (IL)-3, IL-1, IL-6, and granulocyte colony-stimulating factor (G-CSF), on colony formation from primitive progenitors of mice. Cells enriched for cell cycle dormant primitive progenitors were isolated from bone marrow cells of 5-fluorouracil (5-FU)-treated mice by a combination of Nycodenz density gradient separation, immunomagnetic selection for lineage-negative cells, and fluorescence-activated cell sorter (FACS) sorting for Ly-6A/E+Kit+ cells. ML, in the presence of erythropoietin, could support the formation of only a few megakaryocyte colonies. However, ML acted synergistically with SF or IL-3 to support the formation of multiple types of hematopoietic colonies including multilineage colonies. Effects of the combination of ML and SF on multipotential progenitors were not mediated through other cells, as demonstrated by micromanipulation of individual progenitors. In suspension culture, the combination of ML and SF increased the number of multipotential progenitors. ML also acted synergistically with IL-11, IL-6, or G-CSF to support colony formation in serum-containing, but not in serum-free, cultures. However, the multilineage colony formation seen in serum-containing culture was completely abrogated by addition of ACK2, a neutralizing antibody to Kit protein. Serial observation (mapping studies) of colony development from multipotential progenitors suggested that ML triggers the cell division of dormant progenitors. Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G0 period.
Synthese und Reaktionen des 6,11‐Dihydro‐5H‐pyrido[3,2‐c]‐[1] benzazepin‐5‐ons (1989)

Abstract Wir berichten über eine dreistufige Synthese für das neue 6,11‐Dihydro‐5 H ‐pyrido[3,2‐ c ][1]benzazepin‐5‐on ( 6a ) und dessen Derivate 6b–d . Das reaktive Verhalten des Tricyclus wird durch Darstellung der Derivate 7–15 aus der Stammverbindung 6a umrissen. Die Produkte werden durch 1 H‐ und 13 C‐NMR‐Daten charakterisiert.
Vascular brachytherapy: applications in the era of drug-eluting stents. (2002)

Vascular brachytherapy using beta and gamma emitters has revolutionized treatment of in-stent restenosis. We are witnessing a near-abolition of the restenosis problem for simple lesions, but the future of vascular brachytherapy depends on our success in improving efficacy and reducing complications such as late thrombosis and edge effects. Optimizing dosimetry, applying adequate radiation margins, and prolonging antiplatelet therapy should equalize brachytherapy results with those of drug-eluting stents. In this overview we examine issues related to progress and optimization of outcomes derived from the use of vascular brachytherapy. We also examine its potential to expand to other applications beyond in-stent restenosis, such as the treatment of de novo lesions and peripheral vascular disease
Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy (2011)

B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.
Increased juvenile and adult body weights in BALB/cByJ mice reared in a communal nest. (2011)

Both wild and laboratory mice and rats preferentially rear their young in communal nests and indiscriminately nurse any of the young within the nest. In this study, BALBc/ByJ mice reared under communal nesting (CN) conditions (3 dams and their litters sharing a common nest) were compared with BALBc/ByJ mice raised in single (one dam with her litter) nests (SN) in body weight from birth into adulthood; food and water intake and body composition were compared between adult mice. Compared with SN female mice, female CN mice (measured only until weaning) exhibited significantly higher body weights at postnatal days 11 and 25. Male CN mice were significantly heavier than were male SN mice at postnatal day 25 and at 20, 26, and 30 wk of age. There were no differences between adult male mice from CN and SN groups in 48-h food and water intake or body composition (total lean:total fat ratio; measured by quantitative MRI). In conclusion, BALB/cByJ mice reared under communal nesting conditions showed more robust juvenile growth rates than did mice raised with a single dam and litter per cage. In addition, body weights of male CN mice remained higher than male SN mice into adulthood.
Hydrothermal processing of new fly ash cement (1992)

The recent Mount Pinatubo volcanic eruption in the Philippines, in which at least 268 people died, shows that volcanic eruptions can be highly destructive. The eruption shot ash and debris over the countryside; six towns near the volcano faced a high risk of devastating mudslides, and nearly 2000 U.S. service members and their families were evacuated from two nearby military bases. However, this paper reports that not all the consequences of volcanic eruptions are bad. Under hydrothermal conditions, volcanic ash can be transformed into zeolitic tuff and, eventually, into clay minerals that constitute agricultural soils. The Materials Research Laboratory (MRL) has recently used some artificial pozzolanas (fly ash) that when mixed with lime, under hydrothermal conditions, also produced a new type of cementitious material. This was categorized as a new fly ash cement. The formation of a new hydrothermally treated wood-fiber-reinforced composite has also been demonstrated. It is apparent, however, that with respect to concerns about detailed knowledge of the reactivity of calcium silicate-based materials under hydrothermal conditions, the application of the technology far outweighs the understanding of the underlying principles of reactivity. It would seem that an understanding of reactions on the molecular level is just beginning, and that more » work on hydrothermal reactions is still a potentially lucrative area of research. « less
Structure-Based Design of Substituted Piperidines as a New Class of Highly Efficacious Oral Direct Renin Inhibitors (2014)

A cis-configured 3,5-disubstituted piperidine direct renin inhibitor, (syn,rac)-1, was discovered as a high-throughput screening hit from a target-family tailored library. Optimization of both the prime and the nonprime site residues flanking the central piperidine transition-state surrogate resulted in analogues with improved potency and pharmacokinetic (PK) properties, culminating in the identification of the 4-hydroxy-3,5-substituted piperidine 31. This compound showed high in vitro potency toward human renin with excellent off-target selectivity, 60% oral bioavailability in rat, and dose-dependent blood pressure lowering effects in the double-transgenic rat model.
Dynamic Protein-DNA Architecture of a Yeast Heat Shock Promoter (1995)

Here we present an in vivo footprinting analysis of the Saccharomyces cerevisiae HSP82 promoter. Consistent with current models, we find that yeast heat shock factor (HSF) binds to strong heat shock elements (HSEs) in non-heat-shocked cells. Upon heat shock, however, additional binding of HSF becomes apparent at weak HSEs of the promoter as well. Recovery from heat shock results in a dramatic reduction in HSF binding at both strong and weak HSEs, consistent with a model in which HSF binding is subject to a negative feedback regulation by heat shock proteins. In vivo KMnO4 footprinting reveals that the interaction of the TATA-binding protein (TBP) with this promoter is also modulated: heat shock slightly increases TBP binding to the promoter and this binding is reduced upon recovery from heat shock. KMnO4 footprinting does not reveal a high density of polymerase at the promoter prior to heat shock, but a large open complex between the transcriptional start site and the TATA box is formed rapidly upon activation, similar to that observed in other yeast genes.
Nucleotide Sequence, Genome Organization, and Transcription Map of Bovine Adenovirus Type 3 (1998)

The complete DNA sequence of bovine adenovirus type 3 is reported here. The size of the genome is 34,446 bp in length with a G+C content of 54%. All the genes of the early and late regions are present in the expected locations of the genome. However, the late-region genes are organized into seven families, instead of five as they are in human adenovirus type 2. The deduced amino acid sequences of open reading frames (ORFs) in the late regions and early region 2 (E2) and for IVa2 show higher degrees of homology, whereas the predicted amino acid sequences of ORFs in the E1, E3, and E4 regions and the pIX, fiber, and 33,000-molecular-weight nonstructural proteins show little or no homology with the corresponding proteins of other adenoviruses. In addition, the penton base protein lacks the integrin binding motif, RGD, but has an LDV motif instead of an MDV motif. Interestingly, as in other animal adenoviruses, the virus-associated RNA genes appear to be absent from their usual location. Sequence analysis of cDNA clones representing the early- and late-region genes identified splice acceptor and splice donor sites, polyadenylation signals and polyadenylation sites, and tripartite leader sequences.
Immediate antecedents of cigarette smoking: An analysis from ecological momentary assessment. (2002)

The authors assessed the association between smoking and situational cues, including affect, in real-world contexts. Using ecological momentary assessment, 304 smokers monitored ad-lib smoking for 1 week, recording each cigarette on palm-top computers. Generalized estimating equations contrasted 10,084 smoking and 11,155 nonsmoking situations. After controlling for smoking restrictions, smoking was strongly related to smoking urges and modestly related to consumption of coffee and food, the presence of other smokers, and several activities. Smoking was unrelated to negative or positive affect or to arousal, although it was associated with restlessness. Thus, in daily life, affect appears to exert little influence over ad-lib smoking in heavy smoking adults.
A Phase II Trial of nab-Paclitaxel as Second-line Therapy in Patients With Advanced Pancreatic Cancer (2012)

nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy.
Influence of various imperfections on the conversion efficiency of second-harmonic generation in quasi-phase-matching lithium niobate waveguides (1993)

The generation of coherent blue light by frequency doubling of radiation from semiconductor lasers in quasi-phase-matching lithium niobate waveguides has recently been demonstrated, but with a conversion efficiency significantly lower than the theoretically predicted value. We have experimentally investigated the performance of some quasi-phase-matching waveguides by measurements of the second-harmonic power and the integral of the second-harmonic power with respect to the fundamental wavelength at a wavelength scan. These experimental results are combined with a theoretical analysis. It is concluded that the inhomogeneities in the effective index, the absence of domain inversion in some regions along the waveguide, and the suppression of the nonlinearity that is due to the proton exchange process are the most important imperfections to deal with in the future optimization of the domain inversion process and the waveguide formation.