gebhart/patrepeval huggingface dataset:
Reactive Oxygen Species Mediate the Activation of Akt/Protein Kinase B by Angiotensin II in Vascular Smooth Muscle Cells (1999)

Angiotensin II, a hypertrophic/anti-apoptotic hormone, utilizes reactive oxygen species (ROS) as growth-related signaling molecules in vascular smooth muscle cells (VSMCs). Recently, the cell survival protein kinase Akt/protein kinase B (PKB) was proposed to be involved in protein synthesis. Here we show that angiotensin II causes rapid phosphorylation of Akt/PKB (6- +/- 0.4-fold increase). Exogenous H(2)O(2) (50-200 microM) also stimulates Akt/PKB phosphorylation (maximal 8- +/- 0.2-fold increase), suggesting that Akt/PKB activation is redox-sensitive. Both angiotensin II and H(2)O(2) stimulation of Akt/PKB are abrogated by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002 (2(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), suggesting that PI3-K is an upstream mediator of Akt/PKB activation in VSMCs. Furthermore, diphenylene iodonium, an inhibitor of flavin-containing oxidases, or overexpression of catalase to block angiotensin II-induced intracellular H(2)O(2) production significantly inhibits angiotensin II-induced Akt/PKB phosphorylation, indicating a role for ROS in agonist-induced Akt/PKB activation. In VSMCs infected with dominant-negative Akt/PKB, angiotensin II-stimulated [(3)H]leucine incorporation is attenuated. Thus, our studies indicate that Akt/PKB is part of the remarkable spectrum of angiotensin II signaling pathways and provide insight into the highly organized signaling mechanisms coordinated by ROS, which mediate the hypertrophic response to angiotensin II in VSMCs.
Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor (2015)

Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa +/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.
Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA (1996)

Mammalian cells possess a protein complex, termed DNA-PK, which binds to DNA double strand breaks in vitro. The complex consists of the heterodimeric Ku autoantigen and a DNA-dependent protein kinase, DNA-PKcs. Cell lines that are deficient for components of this complex are sensitive to ionizing radiation and have impaired V(D)J recombination, a site-specific recombination process. We have tested these cell lines for their ability to repair double strand breaks in transfected DNA. The xrs-6 cell line, which is deficient for the 80-kDa subunit of the Ku autoantigen, exhibited reduced stability of transfected DNA. Prior to obvious reductions in DNA stability, the levels of homologous recombination and DNA end joining were unaffected. However, the recovery of end joining products with precisely joined ends was reduced, with a concomitant increase in products containing deletions. Unlike the Ku80-deficient cells, no reduction in DNA stability was detected in DNA-PKcs-deficient scid cells. Scid cells also exhibited normal levels of homologous recombination and DNA end joining. These experiments implicate the Ku autoantigen, but not DNA-PKcs, in a direct role in protecting DNA ends from degradation.
Mucosal Plasma Cell Repertoire During HIV-1 Infection (2002)

Impaired development of local Ab responses may predispose HIV-1-infected patients to an increased rate, severity, and duration of mucosal infections. We characterized the repertoire of Ig-producing cells in the intestinal effector compartment (the lamina propria) of HIV-1-infected (n = 29) and seronegative control (n = 27) subjects. The density of Ig-producing cells per area was similar in both groups. However, the proportions of IgA-producing cells were lower in both the duodenum and colon from HIV-1-infected patients compared with those of control subjects (p < 0.05), with compensatory increases in IgG-producing cells in the colon and IgM-producing cells in the duodenum. Similarly, among Abs in the lumen the proportions of IgA were also decreased and the proportions of IgG were increased among HIV-1-infected patients. On a molecular level, V(H) gene repertoire analyses by RT-PCR revealed comparable proportions of the V(H)3 family among duodenal IgA transcripts (50-53%) from both groups. V(H)3 expression was decreased only for IgM among patients with advanced HIV-1 disease (n = 6) compared with that of control subjects (n = 8) (48 +/- 8 vs 62 +/- 13%; p < 0.01). Moreover, the frequencies of individual IgM and IgA V(H)3 genes were comparable in each group, including rates of putative HIV-1 gp120-binding V(H)3 genes (V3-23, V3-30, V3-30/3-30.5). We conclude that, despite a decrement in local IgA producing cells, the density and molecular V(H) repertoire of mucosal plasma cells are relatively intact among patients with HIV-1 infection. These data suggest that HIV-1-infected patients use functional regulatory mechanisms to provide sufficient V(H) diversity and effective induction and differentiation of mucosal B cells.
In‐situ photopolymerization of oriented liquid‐crystalline acrylates, 3. Oriented polymer networks from a mesogenic diacrylate (1989)

Abstract Synthesis, mesomorphism, orientation and photo‐initiated chain crosslinking of the liquid‐crystalline diacrylate 1,4‐phenylene bis{4‐[6‐(acryloyloxy)hexyloxy]benzoate} ( 1 ) are studied. Monomer 1 exhibits a broad nematic phase between 108 and 155°C and a monotropic smectic phase below 88°C. The monomer is uniaxially oriented in its nematic phase at a substrate which has been coated with polyimide and unidirectionally rubbed with tissue. At the transition temperature to the smectic phase the order parameter is measured to be 0,7. During polymerization, the ordering of the mesogens is frozen‐in, yielding a uniaxially crosslinked network. The clear films of oriented poly( 1 ) exhibit a birefringence Δ n between 0,12 and 0,15, depending on the polymerization temperature. In the highest oriented state of 1 a small reduction of the degree of order is observed during the crosslinking reaction, whereas at higher temperatures and lower ordering of 1 , the uniaxially orientation increases upon reaction. A special feature of the oriented networks is that the ordering is maintained while heating at high temperatures. The polymerization of the acrylate groups in the mesomorphic phases proceeds fast and to high conversion. Below 90°C the polymerization behaviour is similar to that of conventional isotropic diacrylates. Above 90°C the polymerization reaction of the liquid‐crystalline diacrylate proceeds faster than that of an isotropic diacrylate.
Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. (1989)

In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF-beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation.
Representational Oligonucleotide Microarray Analysis: A High-Resolution Method to Detect Genome Copy Number Variation (2003)

We have developed a methodology we call ROMA (representational oligonucleotide microarray analysis), for the detection of the genomic aberrations in cancer and normal humans. By arraying oligonucleotide probes designed from the human genome sequence, and hybridizing with "representations" from cancer and normal cells, we detect regions of the genome with altered "copy number." We achieve an average resolution of 30 kb throughout the genome, and resolutions as high as a probe every 15 kb are practical. We illustrate the characteristics of probes on the array and accuracy of measurements obtained using ROMA. Using this methodology, we identify variation between cancer and normal genomes, as well as between normal human genomes. In cancer genomes, we readily detect amplifications and large and small homozygous and hemizygous deletions. Between normal human genomes, we frequently detect large (100 kb to 1 Mb) deletions or duplications. Many of these changes encompass known genes. ROMA will assist in the discovery of genes and markers important in cancer, and the discovery of loci that may be important in inherited predispositions to disease.
Effects of Smoking and Treatment Status on Periodontal Bacteria: Evidence That Smoking Influences Control of Periodontal Bacteria at the Mucosal Surface of the Gingival Crevice (2001)

Smoking-associated periodontitis is not simply a reflection of oral cleanliness. Smoking extends a favorable habitat for bacteria such as P. gingivalis, P. intermedia, and A. actinomycetemcomitans to shallow sites (< or =5 mm). Molecular byproducts of smoking interfere with mechanisms that normally contain growth of damaging bacteria at the surface of the oral mucosa in gingival crevices. In this way, smoking can promote early development of periodontal lesions.
An introduction to epitope prediction methods and software (2008)

In this paper, current prediction methods and algorithms for both T- and B cell epitopes are reviewed, and a comprehensive summary of epitope prediction software and databases currently available online is also provided. This review can offer researchers in this field a sense of direction and insights for future work. However, our main purpose is to introduce clinical and basic biomedical researchers who are not familiar with these biological analysis tools and databases to these online resources and to provide guidance on how to use them effectively.
PPAR-γ agonist rosiglitazone reverses increased cerebral venous hydraulic conductivity during hypertension (2009)

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been shown to protect the cerebral vasculature, including the blood-brain barrier. In the present study, we investigated the effect of the PPAR-gamma agonist rosiglitazone on changes in venous permeability during chronic hypertension induced by nitric oxide synthase inhibition. Female Sprague-Dawley rats were either treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 g/l in drinking water) for 5 wk (HTN; n = 8), L-NAME for 5 wk plus the PPAR-gamma agonist rosiglitazone (20 mg/kg in food) for the last 3 wk (HTN + Rosi; n = 5), L-NAME for 5 wk plus the superoxide dismutase mimetic Tempol (1 mmol/l in drinking water) for the last 3 wk (HTN + Tempol; n = 8), or were untreated controls (n = 9). Fluid filtration (J(v)/S) and hydraulic conductivity (L(p)) of cerebral veins were compared in vitro between groups after a step increase in pressure from 10 to 25 mmHg to mimic the change in hydrostatic pressure during acute hypertension. Hypertension increased J(v)/S by 2.2-fold and L(p) by 3.2-fold. Rosiglitazone treatment after 2 wk of hypertension completely reversed the increased J(v)/S and L(p) that occurred during hypertension, whereas Tempol had no effect. These results demonstrate that rosiglitazone was effective at reversing changes in venous permeability that occurred during chronic hypertension, an effect that does not appear to be related to its antioxidant properties. Our findings suggest that PPAR-gamma may be a key regulator of blood-brain barrier permeability and a potential therapeutic target during hypertension.
Influence of Dietary Compounds on Intestinal Immunity (2000)

This review focuses on the specific effects of nutrients on the intestinal immune system. The intestinal immune system possesses a number of special characteristics different from those of the systemic immune system, which are summarised in this report. Although some of these characteristics are well known, there is a big gap regarding the specific mechanisms that regulate immunity at intestinal level with respect to the systemic immunity. Because of that, during the last years, there is an increasing interest in elucidating the inner mechanisms that regulate the intestinal immune function, as well as how specific nutrients influence that function. We have reviewed this topic with special emphasis on how human milk and its components influence the development of the intestinal immunity in early infancy compared with formula-fed infants. Interactions between nutrients and the intestinal microflora have also been reviewed. Some micronutrients, which are present in human milk and in most of foods, are capable of influencing immune functioning at very low concentrations. The specific action of these micronutrients on some parameters of the intestinal immunity as well as the potential mechanisms of action promoted by them have been considered more in detail. However, few data exist on how other specific nutrients, namely protein and non-protein compounds, lipids, carbohydrates, and others, such as mineral and vitamins, influence the intestinal immunity. Further research in these areas is highly recommended.
Redirecting N-acetylaspartate metabolism in the central nervous system normalizes myelination and rescues Canavan disease (2017)

Canavan disease (CD) is a debilitating and lethal leukodystrophy caused by mutations in the aspartoacylase (<i>ASPA</i>) gene and the resulting defect in <i>N</i>-acetylaspartate (NAA) metabolism in the CNS and peripheral tissues. Recombinant adeno-associated virus (rAAV) has the ability to cross the blood-brain barrier and widely transduce the CNS. We developed a rAAV-based and optimized gene replacement therapy, which achieves early, complete, and sustained rescue of the lethal disease phenotype in CD mice. Our treatment results in a super-mouse phenotype, increasing motor performance of treated CD mice beyond that of WT control mice. We demonstrate that this rescue is oligodendrocyte independent, and that gene correction in astrocytes is sufficient, suggesting that the establishment of an astrocyte-based alternative metabolic sink for NAA is a key mechanism for efficacious disease rescue and the super-mouse phenotype. Importantly, the use of clinically translatable high-field imaging tools enables the noninvasive monitoring and prediction of therapeutic outcomes for CD and might enable further investigation of NAA-related cognitive function.
A Case Study: Maximizing Asset Value Through Integrated Pipeline & Compression Optimization (2004)

ABSTRACT VICO Indonesia is one of three East Kalimantan gas producers, and produces around 1000 MMscf/d from four main fields; Badak, Nilam, Semberah and Mutiara (Fig.1&amp;2). VICO has also been appointed as the Gas Co-ordinator and Pipeline Custodian for East Kalimantan. The main objective of Gas Co-ordination role is to ensure reliable gas supply to the Bontang LNG plant located approximately 60kms north of the Badak Camp. As gas fields mature, there is a requirement for the compressor utilization in each field be optimized. The optimization performed has included in field optimization, integrated intra-field compressor utilization and optimization of the East Kalimantan pipeline network. The target of this optimization is to increase gas deliverability and reserves recovery whilst minimising capital investment. In the past each asset developed its own compression strategy focused on the best value for the asset. For the last 5 years this has been expanded to include the identification of synergies with other assets, i.e. by sharing or removing idle equipment. This year, as a further development, VICO incorporated the East Kalimantan joint operated pipeline network into the optimization to determine a strategy that would give the best value for all the East Kalimantan gas producers. The multi disciplinary study team identified excess compression capacity in one of the assets. The Field Depletion Planning model (FPM), which integrates the subsurface work program with compression and pipeline optimization, was used to identify options for utilization of this excess capacity. Each option was reviewed from the technical and economical standpoint. Gas deliverability, reserves recovery and cost are the key review parameters. The team also considered the impact on the volume of future subsurface work programs and the operational consequences. The study recommended the installation of a small pipeline system modification to allow gas from one field to be compressed at another field. The project not only gives higher gas deliverability and incremental reserves recovery, but also allows flexibility for major pipeline contingency plans. This project is economically justified and could also provide possible future compression utilization for the neighbouring gas producers.
Porous Germanates:  Synthesis, Structure, and Inclusion Properties of Ge7O14.5F2·[(CH3)2NH2]3(H2O)0.86 (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPorous Germanates: Synthesis, Structure, and Inclusion Properties of Ge7O14.5F2·[(CH3)2NH2]3(H2O)0.86Hailian Li, M. Eddaoudi, D. A. Richardson, and O. M. YaghiView Author Information The Department of Chemistry and Biochemistry, Goldwater Center for Science and Engineering Arizona State University, Tempe, Arizona 85287-1604 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8567–8568Publication Date (Web):August 8, 1998Publication History Received23 April 1998Published online8 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja9813919https://doi.org/10.1021/ja9813919rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views786Altmetric-Citations95LEARN 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:Cluster chemistry,Germanium,Materials,Molecules,Solution chemistry Get e-Alerts
Variable-grain and dynamic work generation for Minimal Unique Itemset mining (2008)

SUDA2 is a recursive search algorithm for minimal unique itemset detection. Such sets of items are formed via combinations of non-obvious attributes enabling individual record identification. The nature of SUDA2 allows work to be divided into non-overlapping tasks enabling parallel execution. Earlier work developed a parallel implementation for SUDA2 on an SMP cluster, and this was found to be several orders of magnitude faster than sequential SUDA2. However, if fixed-granularity parallel tasks are scheduled naively in the order of their generation, the system load tends to be imbalanced with little work at the beginning and end of the search. This paper investigates the effectiveness of variable-grained and dynamic work generation strategies for parallel SUDA2. These methods restrict the number of sub-tasks to be generated, based on the criterion of probable work size. The further we descend in the search recursion tree, the smaller the tasks become, thus we only select the largest tasks at each level of recursion as being suitable for scheduling. The revised algorithm runs approximately twice as fast as the existing parallel SUDA2 for finer levels of granularity when variable-grained work generation is applied. The dynamic method, performing level-wise task selection based on size, outperforms the other techniques investigated.
Dyslipidemia and lipid-lowering therapy in the elderly (2005)

According to the current evidence, the fastest growing proportion of patient populations seeking healthcare is those over 65 years of age. Coronary artery disease and subclinical atherosclerosis are highly prevalent in this group of patients and are strongly linked to dyslipidemia, a well-established risk factor for atherosclerosis. Treating dyslipidemia in this group of patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pharmacologic agents in the presence of possible multiple comorbidities. Lifestyle modification remains the first step in the treatment of dyslipidemia; however, it can be difficult to sustain and achieve acceptable compliance in the elderly and it is best used in combination with drug therapy. Statins are widely accepted as the first-line therapy. Several recent studies have demonstrated that statins are safe and effective in the elderly. However, it is important to note that there is very limited data regarding the effects of dyslipidemia treatment on morbidity and mortality in patients over 85 years of age. In summary, the clinicians must recognize that the presence of dyslipidemia in the elderly poses substantial risk of coronary events and stroke. The available evidence has demonstrated that in most elderly patients who are at increased risk for cardiovascular morbidity and mortality, treatment of dyslipidemia with appropriate therapy reduces the risk, and when used carefully with close monitoring for safety, the treatment is generally well tolerated. With increasing life expectancy, it is critical for physicians to recognize the importance of detection and treatment of dyslipidemia in the elderly.