gebhart/patrepeval huggingface dataset:
PPAR-Gamma in Ulcerative Colitis: A Novel Target for Intervention (2013)

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor, originally described in adipose tissue, that controls the expression of a large number of regulatory genes in lipid metabolism and insulin sensitization. Well known by endocrinologists, thiazolidinediones (TZDs) are classical PPARγ synthetic agonists which were currently used as insulin-sensitizing agents in the treatment of type 2 diabetes. While the clinical benefits of TZDs in treating metabolic disorders have been clearly demonstrated, new studies performed in animal models of colitis and in patients with ulcerative colitis have also revealed the key roles of PPARγ activation in the regulation of inflammation and immune response, notably in the colon through epithelial cells. During inflammation, PPAR acts directly to negatively regulate gene expression of proinflammatory genes in a ligand-dependent manner by antagonizing the activities of other transcription factors such as members of the NF-κB and AP-1 families. A major mechanism that underlies the ability of PPARs to interfere with the activities of these transcription factors has been termed transrepression. PPARγ acts by inhibiting signaldependent transcription factors that mediate inflammatory programs of gene activation. However, due to safety issues concerning particularly the greater risk of myocardial infarction, use of TZDs has been severely limited for the treatment of type 2 diabetes and/or inflammatory diseases, justifying the development of a new family of PPARγ agonists with major transrepressive effects and without toxicity. By the demonstration that the anti-inflammatory effects of 5- aminosalicylic acid (5-ASA) in patients with ulcerative colitis were mediated by PPARγ activation, several molecules having 5-ASA similarities have been developed and screened leading to the selection of a aminophenyl-alpha-methoxypropionic acids named GED-0507-34-Levo (GED). This compound activating PPARγ has 100-to 150-fold higher anti-inflammatory activity than 5-ASA. This new PPAR modulator is giving promising results both in vitro and in vivo, without toxicity and is currently evaluated in a phase 2 clinical trial. The aim of this review is to present and discuss the evidence suggesting that PPARγ targeting is of therapeutic interest in the treatment of UC.
Improved Forward-Adaptive Prediction for MPEG-4 Audio Lossless Coding (2005)

This convention paper has been reproduced from the author’s advance manuscript, without editing, corrections, or consideration by the Review Board. The AES takes no responsibility for the contents. Additional papers may be
Tumor necrosis factor-alpha and its second messenger, ceramide, stimulate apoptosis in cultured ovarian follicles. (1996)

In the mammalian ovary, only a small fraction of follicles fully mature and ovulate, while most of them die via apoptosis. Multiple factors promoting follicle survival have been identified, but intraovarian mediators of apoptosis are poorly known. Tumor necrosis factor-alpha (TNF alpha) is a cytokine capable of inducing apoptosis in diverse cell types, and the apoptotic effect of TNF alpha is, partially, coupled to the sphingomyelin signaling pathway with ceramide as a second messenger. Because TNF alpha has been localized in the rat ovary, and TNF alpha treatment increases granulosa cell ceramide production, we studied the effect of treatment with TNF alpha and ceramide on follicle apoptosis. Immature rats were implanted with diethylstilbestrol to stimulate the development of early antral follicles. Follicles were isolated and cultured in a serum-free medium for 24 h with or without hormone treatments. During culture, spontaneous follicle apoptosis occurred (10-fold increase in DNA fragmentation), which was partially blocked by 100 ng/ml FSH (60% suppression). The effect of FSH was counteracted by TNF alpha in a dose-dependent manner, with the maximal effect at 100 ng/ml TNF alpha (90% reversal of FSH action). In situ analysis indicated that the granulosa cell is the follicle cell type undergoing DNA fragmentation. A membrane-permeable ceramide analog, C2-ceramide N-acetyl sphingosine, mimicked the effect of TNF alpha and was able to completely abolish the action of FSH at 50 microM. In contrast, another ceramide analog, C2-dihydroceramide N-acetyl dihydrosphingosine, did not alter the effect of FSH, verifying the specificity of ceramide action. To study the mechanism of TNF alpha and ceramide action, the effect of sodium aurathiomalate (ATM), an inhibitor of interleukin-1 beta-converting enzyme/ced-3-related cystine proteases known to be essential in the execution of mammalian cell apoptosis, was studied. Treatment with ATM (1 mM) prevented the apoptosis-inducing effect of both TNF alpha and ceramide, suggesting a role for cysteine proteases in mediating follicle apoptosis. Treatment with either TNF alpha or ceramide increased both basal and FSH-stimulated progesterone production by cultured follicles. Concomitant treatment by ATM did not alter the stimulatory effect of TNF alpha or ceramide on progesterone production, ruling out nonspecific toxic effect of the inhibitor and indicating that the apoptotic and steroidogenic pathways are independent. In summary, treatment with TNF alpha or its second messenger, ceramide, stimulates apoptosis of early antral follicles in culture, suggesting a potential role for TNF alpha as an intraovarian regulator of follicle atresia by acting through the ceramide signaling pathway.
Expression of ricin B chain in Escherichia coli (1989)

DNA encoding ricin B chain was fused to that encoding the E. coli OmpA signal peptide using the expression secretion vector pIN-111-ompA. When induced, E. coli cells transformed with the recombinant plasmid express ricin B chain. The recombinant product accumulates in the periplasmic space in a soluble, biologically active form.
Ullmann Condensation (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUllmann CondensationHarold WeingartenCite this: J. Org. Chem. 1964, 29, 4, 977–978Publication Date (Print):April 1, 1964Publication History Published online1 May 2002Published inissue 1 April 1964https://pubs.acs.org/doi/10.1021/jo01027a529https://doi.org/10.1021/jo01027a529research-articleACS PublicationsRequest reuse permissionsArticle Views881Altmetric-Citations58LEARN 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
Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial (2013)

Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.
Arthroscopic meniscal repair with fibrin clot of complete radial tears of the lateral meniscus in the avascular zone (1998)

Peripheral lateral meniscal tears are amenable to arthroscopic meniscal repair. However, the posterolateral aspect of the lateral meniscus adjacent to the popliteus tendon is devoid of penetrating peripheral vessels and therefore difficult to heal. A complete radial split at this site is usually treated with total meniscectomy. We report five cases of a tear of the posterolateral aspect of the lateral meniscus anterior to the popliteus fossa. All patients had a radial split that extended to the popliteus tendon. In all cases, the repair was enhanced with a fibrin clot. Second-look arthroscopy showed that healing of the periphery occurred in all of the cases. All patients returned to their initial level of sports activity. Three of five patients were available for follow-up at an average of 71 months, and magnetic resonance imaging was performed at that time to assess the previously repaired meniscus. All menisci were fully healed and showed no further signs of degeneration. The ability of an exogenous fibrin clot to stimulate and support a reparative response in the avascular portion of the meniscus may represent a potential method of repair. Awareness of the relatively low healing potential of this zone and enhancement of healing opportunities should improve outcome.
Fragments of the HIV-1 Tat Protein Specifically Biand TAR RNA (1990)

Proteolytically produced carboxyl-terminal fragments of the human immunodeficiency virus type-1 (HIV-1) Tat protein that include a conserved region rich in arginine and lysine bind specifically to transactivation response RNA sequences (TAR). A chemically synthesized 14-residue peptide spanning the basic subdomain also recognizes TAR, identifying this subdomain as central for RNA interaction. TAR RNA forms a stable hairpin that includes a six-residue loop, a trinucleotide pyrimidine bulge, and extensive duplex structure. Competition and interference experiments show that the Tat-derived fragments bind to double-stranded RNA and interact specifically at the pyrimidine bulge and adjacent duplex of TAR.
Discovery of PDKI, One of the Missing Links in Insulin Signal Transduction (2001)

Historically, two strategies have been used to dissect the insulin signal transduction pathway. One was to start at the insulin receptor and work down the signal transduction pathway from the plasma membrane. The other was to select a physiological action of insulin, namely the mechanism by which insulin stimulates glycogen synthesis, and then work backwards towards the receptor. The hope was that eventually the groups working down from the top of the insulin signalling pathway would meet up with those working upwards from the bottom of the pathway. This has now happened, and in this lecture I will describe the recent advances that have linked the research from both ends of the insulin signal transduction pathway. I will also discuss how these findings have enabled pharmaceutical companies to embark on novel programmes to develop improved therapies for the treatment of diabetes in the future.
Generation of Affibody® ligands binding interleukin‐2 receptor α/CD25 (2008)

Affibody molecules specific for human IL-2Ralpha, the IL-2 (interleukin-2) receptor alpha subunit, also known as CD25, were selected by phage-display technology from a combinatorial protein library based on the 58-residue Protein A-derived Z domain. The IL-2R system plays a major role in T-cell activation and the regulation of cellular immune responses. Moreover, CD25 has been found to be overexpressed in organ rejections, a number of autoimmune diseases and T-cell malignancies. The phage-display selection using Fc-fused target protein generated 16 unique Affibody molecules targeting CD25. The two most promising binders were characterized in more detail using biosensor analysis and demonstrated strong and selective binding to CD25. Kinetic biosensor analysis revealed that the two monomeric Affibody molecules bound to CD25 with apparent affinities of 130 and 240 nM respectively. The Affibody molecules were, on biosensor analysis, found to compete for the same binding site as the natural ligand IL-2 and the IL-2 blocking monoclonal antibody 2A3. Hence the Affibody molecules were assumed to have an overlapping binding site with IL-2 and antibodies targeting the IL-2 blocking Tac epitope (for example, the monoclonal antibodies Daclizumab and Basiliximab, both of which have been approved for therapeutic use). Furthermore, immunofluorescence microscopy and flow-cytometric analysis of CD25-expressing cells demonstrated that the selected Affibody molecules bound to CD4+ CD25+ PMBCs (peripheral-blood mononuclear cells), the IL-2-dependent cell line NK92 and phytohaemagglutinin-activated PMBCs. The potential use of the CD25-binding Affibody molecules as targeting agents for medical imaging and for therapeutic applications is discussed.
Recognition of single-stranded RNA viruses by Toll-like receptor 7 (2004)

Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
Tyrosine phosphorylation of α tubulin in human T lymphocytes (1994)

N-terminal sequencing of the 55- and 50-kDa polypeptides affinity purified on a phosphotyrosine monoclonal antibody column from activated Jurkat T cells identified alpha and beta tubulin. Two-dimensional gel analysis indicated that alpha tubulin was directly phosphorylated on tyrosine. beta Tubulin was not detectably tyrosine phosphorylated but was precipitated by anti-phosphotyrosine (PTyr) antibody by virtue of its association with the alpha subunit as a heterodimer. Phosphotyrosyl alpha tubulin was not incorporated into intact microtubules and was all in the unpolymerized soluble fraction. These results suggest that tyrosine phosphorylation of alpha tubulin may inhibit the ability of this subunit to polymerize into microtubules. Stimulation of Jurkat T cells via T cell receptor increased the amount of tubulin precipitated by the anti-PTyr antibody. These data raise the possibility that the polymerization of tubulin heterodimers may be regulated by phosphorylation on tyrosine during T cell activation.
Replication and virulence of pseudorabies virus mutants lacking glycoprotein gX (1987)

Pseudorabies virus (PRV) glycoprotein gX accumulates in the medium of infected cells. In an attempt to study the function of gX, two viruses were constructed that lacked a functional gX gene. One virus, PRV delta GX1, was derived by insertion of the herpes simplex virus thymidine kinase gene into the gX-coding region. The other virus, PRV delta GXTK-, was derived by subsequent deletion of the inserted herpes simplex virus thymidine kinase gene. Both viruses replicated in cell cultures but produced no gX. Furthermore, PRV delta GX1 was capable of killing mice with a 50% lethal dose of less than 100 PFU.
Gliding Robotic Fish and its Tail-Enabled Yaw Motion Stabilization Using Sliding Mode Control (2013)

Gliding robotic fish is a new type of underwater robots that combines the energy-efficiency of underwater gliders and the high maneuverability of robotic fish. The tail fin of a gliding robotic fish provides the robot more control authority, especially for the lateral motion, compared with traditional underwater gliders. In this paper, the design and development of a gliding robotic fish prototype is first presented, followed by its dynamic model. We then focus on the problem of tail-enabled yaw stabilization during gliding, where a sliding mode controller is proposed. Both simulation and experimental results are demonstrated to validate the effectiveness of the proposed controller.
Observations of trophoblast from normal and pre-eclamptic pregnancies cultured for prolonged periods. (1981)

Trophoblastic cells from normal and pre-eclamptic pregnancies have been cultured for prolonged periods of time in vitro. The growth characteristics, morphology and hormone production in vitro were similar in both. These results suggest that given a comparable environment in vitro, trophoblast from both normal and pre-eclamptic pregnancies does not behave differently. It is suggested, therefore, that the changes classically described in placentae from pre-eclamptic pregnancies are probably secondary to maternal disease rather than a reflection of an altered trophoblast.
Freda Adler (1998)

ABSTRACT This article is a biography of Freda Adler, one of criminology's unique and most accomplished women pioneers. It traces her educational and intellectual background and analyses her contributions to criminological research. It reviews her singular contributions inthe area of women in crime and justice, international and comparative research, and theoretical criminology. Her work has been translated into many languages and has influenced criminological thought globally. Her work on synnomie has stimulated national and international research and enhanced our understanding of the etiology of crime. This article further notes Adler's professional achievements, honors and recognitions by her University, the profession and the public. It chronicles her accomplishments as the President of the American Society of Criminology (1994-1995). It concludes by looking at Freda Adler, the person.
Gene-Modified Human α/β-T Cells Expressing a Chimeric CD16-CD3ζ Receptor as Adoptively Transferable Effector Cells for Anticancer Monoclonal Antibody Therapy (2014)

Abstract The central tumoricidal activity of anticancer monoclonal antibodies (mAb) is exerted by FcγR IIIa (CD16)–expressing effector cells in vivo via antibody-dependent cell-mediated cytotoxicity (ADCC), as observed for natural killer (NK) cells. In practice, chemotherapy-induced leukopenia and exhaustion of NK cells resulting from ADCC often hamper the clinical efficacy of cancer treatment. To circumvent this drawback, we examined in vivo the feasibility of T cells, gene-modified to express a newly generated affinity-matured (158V/V) chimeric CD16-CD3ζ receptor (cCD16ζ-T cells), as a transferable alternative effector for cancer mAb therapy. cCD16ζ-T cells were readily expandable in ex vivo culture using anti-CD2/CD3/CD28 beads and recombinant human interleukin-2 (rhIL-2), and they successfully displayed ADCC-mediated tumoricidal activity in vitro. During ADCC, ligation of opsonized cancer cells to the introduced cCD16ζ-T cells stimulated the effector cells to produce proinflammatory cytokines and release toxic granules through the activation of the Nuclear factor of activated T cells (NFAT) pathway after phosphorylation of the CD3ζ chain. In parallel, these stimulated cCD16ζ-T cells transiently proliferated and differentiated into effector memory T cells. In contrast, NK cells activated by rhIL-2 displayed similar ADCC activity, but failed to proliferate. Human cCD16ζ-T cells infused concomitantly with anti-CD20 mAb synergistically inhibited the growth of disseminated Raji cells, a CD20+ lymphoma cell line, in immunodeficient mice, whereas similarly infused rhIL-2–treated NK cells survived for a shorter time and displayed less effective tumor suppression. Our findings strongly suggest the clinical feasibility of cCD16ζ-T cells as adoptively transferable ADCC effector cells that could potentially enhance the clinical responses mediated by currently available anticancer mAbs. Cancer Immunol Res; 2(3); 249–62. ©2014 AACR.
Two-Dimensional COMSOL Simulation of Heavy-Oil Recovery by Electromagnetic Heating (2009)

Abstract: Introducing heat to the formation has proven to be an effective way of lowering the oil viscosity of heavy oils by raising the temperature in the formation. The application of electrical energy has gained more interest during the last decade because it offers fewer restrictions for its successful application compared to the conventional steam flooding methods [1-2]. Although this recovery technique has been studied before [2-8], there are no commercial reservoir simulators yet available to model the response of a reservoir when it undergoes EM heating. This paper presents the use of COMSOL Multiphysics to simulate single-phase flow in a reservoir when an EM source is applied. Starting from mass and energy balance, and Darcy’s law we modeled the effect on EM heating on temperature, pressure and flow rate for a 2D axis-symmetric system (r and z coordinates). Numerical results from COMSOL Multiphysics [9] were validated with analytical solutions for simplified cases developed earlier [10]. We determined temperatures, pressures and the ultimate oil production obtained from a reservoir when EM heating is applied.
Loss of Heterozygosity at Tumor Suppressor Genes Detectable on Fractionated Circulating Cell-Free Tumor DNA as Indicator of Breast Cancer Progression (2012)

The improved detection of LOH on cell-free DNA provides important information on DNA losses of tumor suppressor genes TIG1, PTEN, cyclin D2, RB1, and BRCA1 in breast cancer. In particular, loss of the cyclin D2 gene might become an important prognostic marker easily detectable in the peripheral blood.