gebhart/patrepeval huggingface dataset:
Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-γ Activity (2010)

OBJECTIVES: Impaired epithelial expression of peroxisome proliferator-activated receptor-γ (PPARγ) has been described in animal colitis models and briefly in patients with ulcerative colitis, but the functional significance in humans is not well defined. We examined PPARγ expression and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone (a PPARγ ligand) in patients with ulcerative colitis. METHODS: Spontaneous and rosiglitazone-mediated PPARγ and adipophillin expression (a gene transcriptionally activated by PPARγ) were measured by reverse transcriptase PCR in colonic biopsies and isolated epithelial cells from patients with ulcerative colitis and controls. Fourteen patients with active distal ulcerative colitis were randomized to either rosiglitazone (4 mg) or mesalazine (1 g) enema treatment once daily for 14 days. RESULTS: PPARγ expression was fourfold reduced in epithelial cells from inflamed compared with uninflamed mucosa and controls. Adipophillin levels were decreased in parallel. Rosiglitazone induced a concentration-dependent increase in adipophillin levels and restored PPARγ activity in epithelial cells from inflamed mucosain vitro. Rosiglitazone enema treatment was well tolerated and reduced the Mayo ulcerative colitis score from 8.9 to 4.3 (P<0.01), similar to the effect of mesalazine. Rosiglitazone increased adipophillin levels in the epithelial cells of the patients, indicating PPARγ activationin vivo. CONCLUSIONS: Roziglitasone enemas improve impaired PPARγ activity in inflamed colonic epithelium and have beneficial clinical effect in patients with active distal ulcerative colitis. These findings raise interest in further studies of PPARγ ligands that exhibit their anti-inflammatory effect locally in the gut to avoid possible systemic side effects.
Seasonal variation of water table and groundwater quality of the karst aquifer of the Jaffna Peninsula-Sri Lanka (2013)

The Miocene limestone bedrock of the Jaffna Peninsula of Sri Lanka extends below the sea level and is an excellent aquifer. The North-East Monsoonal rainfall infiltrates into the soil and forms a layer of freshwater in the limestone above the seawater. This freshwater is in the form of a convex lens, which thins out towards the coast and the lower part of the lens is a transitional zone where the freshwater becomes increasingly brackish with depth. The thickness of the lens diminishes continuously due to the outflow of freshwater into the lagoon/sea along the coastline. Even with this outflow, the freshwater in the lens is able to sustain irrigation and domestic usage till the end of the dry season. The groundwater has an abundance of calcium and bicarbonate ions, the varying concentrations of which affects the pH, causing it to vary from neutral to slightly alkaline. The concentrations of chloride ions increase with the depth of the transition zone as well as towards the coast. The nitrate contents of the well water are higher in the urban areas due to contamination from septic tanks and also in intensively cultivated farm areas where high amounts of nitrogen fertilizers are used. In some wells, both the chloride and nitrate concentrations do exceed the WHO standards for safe drinking water. Thus, the quality of well water is site specific depending on the depth of wells in relation to the transition zone and the surrounding environment. DOI: http://dx.doi.org/10.4038/jnsfsr.v41i1.5326 J.Natn.Sci.Foundation Sri Lanka 2013 41 (1): 3-12
Molecular cloning of human synovial cell collagenase and selection of a single gene from genomic DNA. (1987)

We used a subclone of a rabbit genomic clone for collagenase that cross-hybridizes with human synovial cell messenger RNA (mRNA) to identify a human collagenase complementary DNA (cDNA) clone. The human cDNA clone is 2.1 kilobases (kb) and selects a mRNA transcript of approximately the same size from primary cultures of rheumatoid synovial cells that produce collagenase, but no mRNA is selected from control (nonproducing) synovial fibroblasts. Restriction enzyme analysis and DNA sequence data indicate that our cDNA clone is full length and that it is identical to that recently described for human skin fibroblast collagenase. The cDNA clone identified a single collagenase gene of approximately 17 kb from blots of human genomic DNA. The identity of human skin and synovial cell collagenase and the ubiquity of this enzyme and of its substrates, the interstitial collagens types I, II, and III, imply that common mechanisms controlling collagenolysis throughout the human body may be operative in both normal and disease states.
Lipopolysaccharide-enhanced, Toll-like Receptor 4–dependent T Helper Cell Type 2 Responses to Inhaled Antigen (2002)

Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.
Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells (2007)

Compelling evidence has now demonstrated that IL-17-producing CD4 cells (Th17) are a major contributor to autoimmune pathogenesis, whereas CD4+CD25+ T regulatory cells (Treg) play a major role in suppression of autoimmunity. Differentiation of proinflammatory Th17 and immunosuppressive Treg from naive CD4 cells is reciprocally related and contingent upon the cytokine environment. We and others have reported that in vivo administration of pertussis toxin (PTx) reduces the number and function of mouse Treg. In this study, we have shown that supernatants from PTx-treated mouse splenic cells, which contained IL-6 and other proinflammatory cytokines, but not PTx itself, overcame the inhibition of proliferation seen in cocultures of Treg and CD4+CD25- T effector cells. This stimulatory effect could be mimicked by individual inflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha. The combination of these cytokines synergistically stimulated the proliferation of CD4+CD25- T effector cells despite the presence of Treg with a concomitant reduction in the percentage of FoxP3+ cells and generation of IL-17-expressing cells. PTx generated Th17 cells, while inhibiting the differentiation of FoxP+ cells, from naive CD4 cells when cocultured with bone marrow-derived dendritic cells from wild-type mice, but not from IL-6-/- mice. In vivo treatment with PTx induced IL-17-secreting cells in wild-type mice, but not in IL-6-/- mice. Thus, in addition to inhibiting the development of Treg, the immunoadjuvant activity of PTx can be attributable to the generation of IL-6-dependent IL-17-producing CD4 cells.
CPU reservations and time constraints (1997)

Article Free Access Share on CPU reservations and time constraints: efficient, predictable scheduling of independent activities Authors: Michael B. Jones Microsoft Research, Microsoft Corporation, One Microsoft Way, Building 9s/1, Redmond, WA Microsoft Research, Microsoft Corporation, One Microsoft Way, Building 9s/1, Redmond, WAView Profile , Daniela Roşu College of Computing, Georgia Institute of Technology, Atlanta, GA College of Computing, Georgia Institute of Technology, Atlanta, GAView Profile , Marcel-Cătălin Roşu View Profile Authors Info & Claims SOSP '97: Proceedings of the sixteenth ACM symposium on Operating systems principlesOctober 1997Pages 198–211https://doi.org/10.1145/268998.266689Published:01 October 1997Publication History 213citation1,484DownloadsMetricsTotal Citations213Total Downloads1,484Last 12 Months58Last 6 weeks12 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Contraceptive vaccine assessment based on a murine ZP3 mini-autoantigen (1994)

A summary is presented of published and some unpublished observations from studies on the immunological response of mice to a 13-mer peptide of the murine ovarian zona pellucida glycoprotein ZP3. The findings have the following implications for the design of immunocontraceptive vaccines. To be reversible, a ZP3 vaccine must not contain pathogenic T cell epitopes of ZP3, but contraception without autoimmune oophoritis may be feasible. The immune response to the ZP3 mini-autoantigen is highly variable among inbred mouse strains, suggesting that a single oophoritogenic peptide would not achieve irreversible contraception in an outbred population. The discovery of antigen mimicry at the level of T cell peptide has thrown doubt on the validity of current strategy in detecting relevant self-antigens that might cross react with vaccine immunogens and on the feasibility of fully predicting the cross-reactive autoimmunogenic potential of a peptide or polypeptide vaccine antigen. Autoantibodies directed against epitopes outside the ZP3 mini-autoantigen, produced by immunization with the pure T cell epitope, react with high affinity, with native zona pellucida, and may be useful in identifying B cell epitopes in ZP3.
Anisotropic etching of silicon (1978)

Anisotropic etching of silicon has become an important technology in silicon semiconductor processing during the past ten years. It will continue to gain stature and acceptance as standard processing technology in the next few years. Anisotropic etching of (100) orientation silicon is being widely used today and (110) orientation technology is emerging. This paper discusses both orientation-dependent and concentration-dependent etching of (100) and (110) silicon. Very exact process control steps may be designed into a process by use of (100) anisotropic and concentration-dependent etching. Also, methods of oxide or nitride pin hole detection in (100) silicon are presented. Mask alignments to obtain different etch front termination in both (100) and (110) silicon are shown. Very high packing density structures, less than 1 μm, are obtained in the (110) technology, and extremely high etching ratios of greater than 650 to 1 are obtained in (110) orientation-dependent etching. Some of the many applications for anisotropic and concentration-dependent etching are described.
Cellular FLIP (Long Form) Regulates CD8+ T Cell Activation through Caspase-8-Dependent NF-κB Activation (2005)

Cellular FLIP long form (c-FLIP(L)) was originally identified as an inhibitor of Fas (CD95/Apo-1). Subsequently, additional functions of c-FLIP(L) were identified through its association with receptor-interacting protein (RIP)1 and TNFR-associated factor 2 to activate NF-kappaB, as well as by its association with and activation of caspase-8. T cells from c-FLIP(L)-transgenic (Tg) mice manifest hyperproliferation upon activation, although it was not clear which of the various functions of c-FLIP(L) was involved. We have further explored the effect of c-FLIP(L) on CD8(+) effector T cell function and its mechanism of action. c-FLIP(L)-Tg CD8(+) T cells have increased proliferation and IL-2 responsiveness to cognate Ags as well as to low-affinity Ag variants, due to increased CD25 expression. They also have a T cytotoxic 2 cytokine phenotype. c-FLIP(L)-Tg CD8(+) T cells manifest greater caspase activity and NF-kappaB activity upon activation. Both augmented proliferation and CD25 expression are blocked by caspase inhibition. c-FLIP(L) itself is a substrate of the caspase activity in effector T cells, being cleaved to a p43(FLIP) form. p43(FLIP) more efficiently recruits RIP1 than full-length c-FLIP(L) to activate NF-kappaB. c-FLIP(L) and RIP1 also coimmunoprecipitate with active caspase-8 in effector CD8(+) T cells. Thus, one mechanism by which c-FLIP(L) influences effector T cell function is through its activation of caspase-8, which in turn cleaves c-FLIP(L) to allow RIP1 recruitment and NF-kappaB activation. This provides a partial explanation of why caspase activity is required to initiate proliferation of resting T cells.
Neurobehavioral changes associated with caudate lesions (1989)

We report behavioral and cognitive characteristics of 12 patients with caudate nuclei lesions, 11 unilateral and one bilateral. These patients developed an acute behavioral change characterized by apathy, disinhibition, or a major affective disturbance. The pattern of personality change correlated with size and location of lesion within the caudate but not the laterality. Seven patients were further compared with matched controls on a series of neuropsychological tests. Their performance was impaired on tasks requiring planning and sequencing. They had short attention spans and decreased free recall of episodic and semantic items with good recognition memory scores. Similar behavioral and cognitive changes also occur in early Huntington's disease, frontal-lesioned patients, and caudate-lesioned animals, and correspond to disturbances of specific frontal-caudate circuits. These results implicate the caudate nuclei in mediating prefrontal behaviors and possibly in the conceptual integration of memories.
Object tracking in low-frame-rate video (2005)

In this paper, we present an object detection and tracking algorithm for low-frame-rate applications. We extend the standard mean-shift technique such that it is not limited within a single kernel but uses multiple kernels centered around high motion areas obtained by change detection. We also improve the convergence properties of the mean-shift by integrating two additional likelihood terms. Our simulations prove the effectiveness of the proposed method.
Electrochemical pretreatment of glassy carbon electrodes (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical pretreatment of glassy carbon electrodesRoyce C. EngstromCite this: Anal. Chem. 1982, 54, 13, 2310–2314Publication Date (Print):November 1, 1982Publication History Published online1 May 2002Published inissue 1 November 1982https://pubs.acs.org/doi/10.1021/ac00250a038https://doi.org/10.1021/ac00250a038research-articleACS PublicationsRequest reuse permissionsArticle Views3747Altmetric-Citations314LEARN 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
A Walk Through the Planned CS Building (1991)

Using the architectural plan views of our future CS building as test objects, we have completed the first stage of a Building walkthrough system. The inputs to our system are AutoCAD files. An AutoCAD converter translates the geometrical information in these files into a format suitable for 3D rendering. Major model errors, such as incorrect polygon intersections and random face orientations, are detected and fixed automatically. Interactive viewing and editing tools are provided to view the results, to modify and clean the model and to change surface attributes. &lt;p&gt;Our display system provides a simple-to-use user interface for interactive exploration of buildings. Using only the mouse buttons, the user can move inside and outside the building and change floors. Several viewing and rendering options are provided, such as restricting the viewing frustum, avoiding wall collisions, and selecting different rendering algorithms. A plan view of the current floor, with the position of the eye point and viewing direction on it, is displayed at all times. The scene illumination can be manipulated, by interactively controlling intensity values for 5 light sources. &lt;p.We have improved the rendering speed of our system by subdividing the model into cells and reducing the fraction of the building that is sent to the rendering pipeline at display time. Each floor is divided into approximately room-sized cells, each with a precomputed cell-to-cell visibility list. During display, the cell containing the viewpoint is identified, and the contents of the potentially visible cells are retrieved from storage. This set is further reduced by culling it against the observers view frustum. The contents of the remaining cells are then sent to the graphics pipeline
A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities (1997)

A chimeric gene was constructed from the genes coding for the human complement regulatory proteins, membrane cofactor protein (CD46) and decay-accelerating factor (CD55). The recombinant chimeric gene was transfected into Chinese hamster ovary cells. The gene product is a soluble, glycosylated, 110-kDa protein named complement activation blocker-2 (CAB-2). This protein possesses both factor I cofactor activity and decay-accelerating activity, and inactivates classical and alternative C3/C5 convertases in vitro. The specific activity of CAB-2 against cell-associated convertases is greater than that of soluble forms of either membrane cofactor protein or decay-accelerating factor or of both factors combined. CAB-2 also blocks the activation of complement in vivo, inhibiting both the Arthus reaction and Forssman shock in guinea pigs. Studies in rats demonstrate CAB-2 to exhibit favorable biphasic pharmacokinetics with a t1/2 alpha of 10 min and a t1/2 beta of 8 h; the beta phase accounts for 93% of the administered dose. CAB-2 may be an effective therapeutic treatment of acute human diseases in which excessive complement activation causes damage to normal tissues.
Tuning the Moenomycin Pharmacophore To Enable Discovery of Bacterial Cell Wall Synthesis Inhibitors (2013)

New antibiotic drugs need to be identified to address rapidly developing resistance of bacterial pathogens to common antibiotics. The natural antibiotic moenomycin A is the prototype for compounds that bind to bacterial peptidoglycan glycosyltransferases (PGTs) and inhibit cell wall biosynthesis, but it cannot be used as a drug. Here we report the chemoenzymatic synthesis of a fluorescently labeled, truncated analogue of moenomycin based on the minimal pharmacophore. This probe, which has optimized enzyme binding properties compared to moenomycin, was designed to identify low-micromolar inhibitors that bind to conserved features in PGT active sites. We demonstrate its use in displacement assays using PGTs from S. aureus, E. faecalis, and E. coli. 110,000 compounds were screened against S. aureus SgtB, and we identified a non-carbohydrate based compound that binds to all PGTs tested. We also show that the compound inhibits in vitro formation of peptidoglycan chains by several different PGTs. Thus, this assay enables the identification of small molecules that target PGT active sites, and may provide lead compounds for development of new antibiotics.
RNA Interference and Potential Applications (2006)

RNA interference (RNAi) is the process of using specific sequences of double-stranded RNA (dsRNA) to knock down the expression level of sequence-homologous genes. Such ability of small interfering RNA (siRNA) in mammalian cells will undoubtedly revolutionize the study of functional genomics, the discovery of drug targets and even the treatment of human diseases. In this review we briefly describe the history of RNAi discovery, the RNAi mechanism and the general guideline for siRNA design as well as various methods for siRNA production and delivery. We also introduce the potential applications of siRNA, inducible siRNA and siRNA library in speeding up basic biomedical research and in acting as potential therapeutic agents for treatment of numerous human diseases.
Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression (2008)

TGF-beta and its signaling mediators, Smad2, -3, and -4, are involved with tumor suppression and promotion functions. Smad4-/- mouse epidermis develops spontaneous skin squamous cell carcinomas (SCCs), and Smad3-/- mice are resistant to carcinogen-induced skin cancer; however, the role of Smad2 in skin carcinogenesis has not been explored. In the present study, we found that Smad2 and Smad4, but not Smad3, were frequently lost in human SCCs. Mice with keratinocyte-specific Smad2 deletion exhibited accelerated formation and malignant progression of chemically induced skin tumors compared with WT mice. Consistent with the loss of Smad2 in poorly differentiated human SCCs, Smad2-/- tumors were poorly differentiated and underwent epithelial-mesenchymal transition (EMT) prior to spontaneous Smad4 loss. Reduced E-cadherin and activation of its transcriptional repressor Snail were also found in Smad2-/- mouse epidermis and occurred more frequently in Smad2-negative human SCCs than in Smad2-positive SCCs. Knocking down Snail abrogated Smad2 loss-associated EMT, suggesting that Snail upregulation is a major mediator of Smad2 loss-associated EMT. Furthermore, Smad2 loss led to a significant increase in Smad4 binding to the Snail promoter, and knocking down either Smad3 or Smad4 in keratinocytes abrogated Smad2 loss-associated Snail overexpression. Our data suggest that enhanced Smad3/Smad4-mediated Snail transcription contributed to Smad2 loss-associated EMT during skin carcinogenesis.
Diffusional Mobility of Golgi Proteins in Membranes of Living Cells (1996)

The mechanism by which Golgi membrane proteins are retained within the Golgi complex in the midst of a continuous flow of protein and lipid is not yet understood. The diffusional mobilities of mammalian Golgi membrane proteins fused with green fluorescent protein from Aequorea victoria were measured in living HeLa cells with the fluorescence photobleaching recovery technique. The diffusion coefficients ranged from 3 x 10(-9) square centimeters per second to 5 x 10(-9) square centimeters per second, with greater than 90 percent of the chimeric proteins mobile. Extensive lateral diffusion of the chimeric proteins occurred between Golgi stacks. Thus, the chimeras diffuse rapidly and freely in Golgi membranes, which suggests that Golgi targeting and retention of these molecules does not depend on protein immobilization.