gebhart/patrepeval huggingface dataset:
IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells (2004)

CD25(+)CD4(+) regulatory T cells inhibit the activation of autoreactive T cells in vitro and in vivo, and suppress organ-specific autoimmune diseases. The mechanism of CD25(+)CD4(+) T cells in the regulation of experimental autoimmune encephalomyelitis (EAE) is poorly understood. To assess the role of CD25(+)CD4(+) T cells in EAE, SJL mice were immunized with myelin proteolipid protein (PLP)(139-151) to develop EAE and were treated with anti-CD25 mAb. Treatment with anti-CD25 antibody following immunization resulted in a significant enhancement of EAE disease severity and mortality. There was increased inflammation in the central nervous system (CNS) of anti-CD25 mAb-treated mice. Anti-CD25 antibody treatment caused a decrease in the percentage of CD25(+)CD4(+) T cells in blood, peripheral lymph node (LN) and spleen associated with increased production of IFN-gamma and a decrease in IL-10 production by LN cells stimulated with PLP(130-151) in vitro. In addition, transfer of CD25(+)CD4(+) regulatory T cells from naive SJL mice decreased the severity of active EAE. In vitro, anti-CD3-stimulated CD25(+)CD4(+) T cells from naive SJL mice secreted IL-10 and IL-10 soluble receptor (sR) partially reversed the in vitro suppressive activity of CD25(+)CD4(+) T cells. CD25(+)CD4(+) T cells from IL-10-deficient mice were unable to suppress active EAE. These findings demonstrate that CD25(+)CD4(+) T cells suppress pathogenic autoreactive T cells in actively induced EAE and suggest they may play an important natural regulatory function in controlling CNS autoimmune disease through a mechanism that involves IL-10.
Studies on nucleosides and nucleotides. LXXXIX. Purine cyclonucleosides. (43). Synthesis and properties of 2'-halogeno-2'-deoxyguanosines. (1981)

The reaction of N2-isobutyryl-9-(2'-O-trifluoromethanesulfonyl-3', 5'-di-O-tetrahydrofuranyl-β-D-arabinofuranosyl) guanine with tetra-n-butylammonium fluoride or an appropriate metal halide in dimethylformamide aftorded N2-isobutyryl-3', 5'-di-O-tetrahydrofuranyl-2'-halogeno-2'-deoxyguanosines. The deprotection of these products led to 2'-halogeno-2'-deoxyguanosines. The ultraviolet absorption properties, 1H and 13C nuclear magnetic resonance spectral properties of the products were recorded.
Immunizations of monkeys with synthetic peptides disclose conserved areas on gp120 of human immunodeficiency virus type 1 associated with cross-neutralizing antibodies and T-cell recognition. (1991)

Site-directed immunization was employed to identify sites on the envelope glycoprotein gp120 for antibody-mediated neutralization of human immunodeficiency virus type 1 (HIV-1). Antisera were raised in monkeys (Macaca fascicularis) against a series of 40 overlapping synthetic peptides covering the entire amino acid sequence of gp120 from the HTLV-IIIB strain of HIV-1. Immune sera against 12 of these peptides were reactive with gp120 by immunoblotting analysis, and antisera raised against 5 peptides, corresponding to amino acids (aa) 152-176, 193-218, 206-230, 248-269, and 307-330, were highly efficient in neutralizing HIV-1 (HTLV-IIIB) infectivity in vitro. Admixture of individual neutralizing anti-peptide monkey sera resulted in increment in neutralizing antibody titer. Antisera with reactivity to the relatively conserved regions defined by aa 152-176, 193-230, and 248-269 also neutralized to different extents the infectivity of the five Swedish clinical isolates of HIV-1 tested. Only a few HIV-1-infected people were found to make antibodies to these three conserved domains of gp120 as judged by ELISA using synthetic peptides as antigens. Three of the peptides (aa 152-176, 248-269, and 307-330) that induced neutralization antibodies also induced interleukin 2 production and lymphocyte proliferation when added to cultures of peripheral blood mononuclear cells from monkeys immunized with the corresponding peptides, indicating that these domains accommodate T-cell recognition sites. The results have obvious implications for the rational design of subunit vaccines against HIV-1 infection.
Characterization of a late phase pulmonary response after antigen challenge in allergic sheep. (1983)

We determined if allergic sheep undergo a dual bronchoconstriction in response to inhalation of antigen and whether these responses could be modified by cromolyn or glucocorticosteroids. In 8 conscious sheep with Ascaris suum hypersensitivity, mean pulmonary flow resistance (RL), dynamic lung compliance (Cdyn), thoracic gas volume (Vtg), and arterial oxygen tension (PaO2) were determined prior to, immediately after, and from 2 through 8 h after and 24 h after inhalation challenge with Ascaris suum antigen. Immediately after antigen challenge, mean specific lung resistance (SRL = RL X Vtg) increased by 750% (p less than 0.01) and mean Cdyn and PaO2 decreased by 55% (p less than 0.01) and 37% (p less than 0.01), respectively. By 5 h after challenge, mean SRL and PaO2 had returned to baseline values, whereas mean Cdyn was still below baseline (-19%, p less than 0.05). At 6.5 h, mean SRL increased again to 245% (p less than 0.01) of baseline and remained significantly elevated through the eighth hour. The average increase in mean SRL for the 6.5- to 8-h postchallenge period was 196%, with concomitant decreases in mean Cdyn and PaO2 of 29% and 10%, respectively. By 24 h, all values had returned to baseline. Control inhalation challenge with ragweed, an antigen to which sheep are not sensitive, did not significantly alter SRL, Cdyn, or PaO2 at any time during the 8-h observation period, indicating that the late response was antigen specific and not caused by circadian rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)
Production of env-deficient rous sarcoma virus (RSV) early after infection. (1997)

Production of defective virus particles during the early stage of Rous sarcoma virus (RSV) infection of chicken embryo fibroblasts (CEF) was examined. RSV harvested 2 days post infection (2pi) had 10 to 30 times lower specific infectivity (focus forming units/unit reverse transcriptase activity) than 5pi harvest. Virus particles produced on day 2 contained less env proteins than particles harvested on day 5. The amount of other viral proteins was equal in particles harvested on day 2 and day 5. Analysis of infected cells revealed that these cells synthesized less env proteins on day 2 than on day 5. RSV RNA in infected cells was spliced normally on day 2. Infection at a low multiplicity of infection (moi) prolonged the production of defective particles. When infection was initiated by a low moi (0.01), particles harvested on day 5 had the same characteristics as 2pi particles after infection with a high moi (1.0). We conclude that the low infectivity of early harvest is due to the reduced amount of env proteins in virus particles, which is a consequence of the reduced env protein synthesis.
An evaluation of clusterin antisense inhibitor OGX-011 in combination with the second-generation antiandrogen MDV3100 in a castrate-resistant prostate cancer model. (2011)

4502 Background: Experimental evidence strongly implicate the AR and intra-tumoral androgen synthesis in promoting tumor cell survival and development of castrate resistant prostate cancer (CRPC). The new second generation AR antagonist, MDV3100, has shown activity in preclinical and clinical studies. Our previous studies link androgen ablation therapy with clusterin upregulation and castrate resistance, and we developed the antisense inhibitor, OGX-011, that synergistically enhances both castration and chemotherapies in prostate cancer (CaP) models. In this study, we tested whether OGX-011 sensitized MDV3100 and delayed progression in castrate-resistant LNCaP model. Methods: Effects of single vs combination MDV3100 and OGX-011 regimens on AR-positive LNCaP cell growth rates, protein, and gene expression were analyzed using crystal violet assay, flow cytometry, western blotting and RT-PCR, respectively. AR transcriptional activity was measured by PSA-luciferase reporter assay, while AR degradation was assessed by cycloheximide chase assay. The effects combination treatment on castrate-resistant LNCaP tumor growth was assessed in castrated male athymic mice. Results: Combination OGX-011 + MDV3100 showed synergistic effect and more potently suppressed LNCaP cell growth rates in a dose and time dependent manner compared to OGX-011 or MDV3100 monotherapy. As negative controls, no synergism was seen in AR negative PC3 cells. PARP cleavage, sub G0/G1 apoptotic fraction and repressed AKT phosphorylation was most enhanced with combined therapy. Interestingly, OGX-011 accelerated AR degradation and repressed AR transcriptional activity in combination with MDV3100. In vivo, combined OGX-011 + MDV3100 significantly delayed castration-resistant LNCaP tumor progression and PSA progression compared to scramble oligonucleotide + MDV3100 (p<0.05 and p<0.05 at 12weeks, respectively). Conclusions: OGX-011 combined with MDV3100 down-regulated AR levels and activity and suppressed castrate resistant LNCaP cell growth in vitro and in vivo, providing pre-clinical proof-of-principle as a promising approach for AR targeting therapy in CRPC.
Self‐diffusion of water in cartilage and cartilage components as studied by pulsed field gradient NMR (1999)

Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) was used to investigate the self-diffusion behavior of water molecules in cartilage, polymeric cartilage components, and different model polymers. The short-time self-diffusion coefficients (diffusion time D 13 msec) are found to decrease steadily with decreasing water content. This holds equally well for cartilage and cartilage components. The short-time diffusion coefficients are subjected to a rather nonspecific obstruction effect and mainly depend on the water content of the sample. The long-time diffusion coefficients in cartilage ( D 500 msec), however, reflect structural properties of this tissue. Measurements with varying observation times as well as experiments involving enzymatic treatment of articular cartilage suggest that the collagenous network in cartilage is likely to be responsible for the observed restricted diffusion.
A scalable front-end architecture for fast instruction delivery (1999)

In the pursuit of instruction-level parallelism, significant demands are placed on a processor's instruction delivery mechanism. Delivering the performance necessary to meet future processor execution targets requires that the performance of the instruction delivery mechanism scale with the execution core. Attaining these targets is a challenging task due to I-cache misses, branch mispredictions, and taken branches in the instruction stream. To further complicate matters, a VLSI interconnect scaling trend is materializing that further limits the performance of front-end designs in future generation process technologies.To counter these challenges, we present a fetch architecture that permits a faster cycle time than previous designs and scales better with future process technologies. Our design, called the Fetch Target Buffer, is a multi-level fetch block-oriented predictor. We decouple the FTB from the instruction fetch and decode pipelines to afford it the fastest clock possible. Through cycle-based simulation and circuit-level delay analysis, we find that our multi-level FTB design is capable of delivering instructions 25% faster than the best single-level BTB-based pipeline configuration. Moreover, we show that our design scales better to future process technologies than traditional single-level designs.
The physiological role of the polyamines (2000)

BACKGROUND: The detection of important immunocompetence-like features on endocrine steroid cells raises questions about direct intercellular communication between the adrenal and immune systems. This article summarizes our recent work and new data on immune-adrenal interactions. MATERIALS AND METHODS: RT-PCR and immunohistochemistry were performed to examine MHC class II (HLA-DR) expression in adrenocortical tumours. Coculture systems of NCI-H295 adrenocortical carcinoma cells and HLA-matched lymphocytes were used to examine effects on steroid production and survival of lymphocytes. RESULTS: HLA-DR m-RNA is found in both benign and malignant adrenals, except the NCI-H295 cell line. Under direct coculture conditions with NCI-H295 cell line, spontaneous apoptosis of immune cells was reduced. Synthesis of cortisol and especially of dehydroepiandrosterone production of tumour cells was markedly increased. Differences by separating CD4- and CD8- T cells were not detected. CONCLUSIONS: Direct cellular contact between lymphocytes and adrenocortical cells seems to be involved in the peripheral regulation of androgen synthesis in the adrenal. The molecular basis of this interaction is not known. With regard to normal adrenals, ligation of MHC class II antigens could be a potential mechanism for a peripheral regulation of androgen secretion.
A Tandem Orthogonal Proteolysis Strategy for High-Content Chemical Proteomics (2005)

The field of proteomics aims to assign functions to the numerous protein products encoded by eukaryotic and prokaryotic genomes. Toward this end, chemical strategies have emerged as a powerful means to enrich specific classes of proteins based on shared functional properties, such as catalytic activity [activity-based protein profiling (ABPP)], and post-translational modification state. The theoretical information content in chemical proteomic experiments greatly exceeds the actual data procured, due in large part to limitations in existing analytical technologies. Here, we present a tandem orthogonal proteolysis (TOP) strategy for high-content chemical proteomics that enables the parallel characterization of probe-labeled proteins and sites of probe modification. The TOP approach exploits "click chemistry" to introduce a multifunctional tag onto probe-labeled proteins that contains both a biotin group for protein enrichment and a tobacco etch virus (TEV) protease cleavage site for selective release of probe-modified peptides. Following capture on streptavidin beads, protein targets of probes and their sites of labeling are sequentially identified by a two-step proteolysis strategy (trypsin and TEV, respectively). We apply the TOP method to characterize targets of sulfonate ester ABPP probes in tissue proteomes, resulting in the discovery of numerous active site-labeled enzymes. Enzymes modified on regulatory sites and proteins of unknown function were also identified. These findings indicate that a wide range of functional residues are targeted by sulfonate ester probes and highlight the value of TOP-based chemical proteomics for the characterization of proteins and the residues that regulate their activity.
Breaking the Rules? Judicial Discourse on Asylum Seekers, 1992-2002 (2007)

Over the decade from mandatory detention (1992) to the 'Pacific Solution' (2001), I trace the tension between national sovereignty and human rights discourse. The codification of the Migration Act 1958 in 1989 led to legislative enactment of immigration restriction laws pertaining to refugees, as well as discriminatory and arbitrary provisions concerning their presence in Australia, which, under the Constitution, the judiciary cannot strike down, but can only review on a case by case basis for errors of law in decision making.
Gel electrophoretic mobility of single-stranded DNA: The two reptation field-dependent factors (2000)

The reptation model is the dominant theory in understanding the electrophoretic separation of single-stranded DNA molecules in gels or entangled polymer solutions. Recently, we showed that the Ogston and reptation regimes are separated by an entropic trapping regime at low field intensities. Here, we report the first comparison of the field-dependent part of the DNA mobility for both small and long reptating molecules. We show that both mobilities increase linearly with field intensity, with the mobility of the longer (comigrating) fragments increasing faster than that of the smaller ones. We compare our results to the predictions of the biased reptation model.
Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy (2004)

Cardiac hypertrophy involves increased mass (growth) of the heart and a cardinal feature of this condition is increased rates of protein synthesis. Several signaling pathways have been implicated in cardiac hypertrophy including the phosphatidylinositol 3-kinase (PI3K) and Ras/Raf/MEK/Erk pathways. PI3K lies upstream of the mammalian target of rapamycin (mTOR), an important positive regulator of protein synthesis and cell growth. However, recent data suggest that, in response to certain hypertrophic agents, signaling via Ras and MEK/Erk, as well as mTOR, is required for activation of protein synthesis, indicating new connections between these key signaling pathways.
Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. (1996)

Repeated measures ANOVA, t-test (significance: p < 0.05). A clear and early (peak: 15-30 min) GLP-1[7-36 amide] response was observed in all subjects, without any significant difference between gut-resected and control groups (p = 0.95). There were no significant differences in oral glucose tolerance (p = 0.21) or in the suppression of pancreatic glucagon (p = 0.36). Colonectomized patients had a higher insulin (p = 0.011) and C-peptide (p = 0.0023) response in comparison to all other groups. GIP responses also were higher in the colonectomized patients (p = 0.0005). Inactive Crohn's disease and resections of the small intestine as well as proctocolectomy did not change overall GLP-1[7-36 amide] responses and especially not the early increment after oral glucose. This may indicate release of GLP-1[7-36 amide] after oral glucose from the small number of GLP-1[7-36 amide] producing L-cells in the upper gut rather than from the main source in the ileum, colon and rectum. Colonectomized patients are characterized by insulin hypersecretion, which in combination with their normal oral glucose tolerance possibly indicates a reduced insulin sensitivity in this patient group. GIP may play a role in mediating insulin hypersecretion in these patients.
Synthetic Emulsifying Agents (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic Emulsifying AgentsMary Fieser, Louis F. Fieser, Edmond Toromanoff, Yoshimasa Hirata, Hans Heymann, Melvin Tefft, and Sivaprasad BhattacharyaCite this: J. Am. Chem. Soc. 1956, 78, 12, 2825–2832Publication Date (Print):June 1, 1956Publication History Published online1 May 2002Published inissue 1 June 1956https://pubs.acs.org/doi/10.1021/ja01593a049https://doi.org/10.1021/ja01593a049research-articleACS PublicationsRequest reuse permissionsArticle Views573Altmetric-Citations54LEARN 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
Real-Time Quantitative PCR for Human Herpesvirus 6 DNA (2000)

The diagnosis of human herpesvirus 6 (HHV-6) infection represents a complex issue because the most widely used diagnostic tools, such as immunoglobulin G antibody titer determination and qualitative DNA PCR with blood cells, are unable to distinguish between latent (clinically silent) and active (often clinically relevant) infection. We have developed a new, highly sensitive, quantitative PCR assay for the accurate measurement of HHV-6 DNA in tissue-derived cell suspensions and body fluids. The test uses a 5' nuclease, fluorogenic assay combined with real-time detection of PCR amplification products with the ABI PRISM 7700 sequence detector system. The sensitivity of this method is equal to the sensitivity of a nested PCR protocol (lower detection limit, 1 viral genome equivalent/test) for both the A and the B HHV-6 subgroups and shows a wider dynamic range of detection (from 1 to 10(6) viral genome equivalents/test) and a higher degree of accuracy, repeatability, and reproducibility compared to those of a standard quantitative-competitive PCR assay developed with the same reference DNA molecule. The novel technique is versatile, showing the same sensitivity and dynamic range with viral DNA extracted from different fluids (i.e., culture medium or plasma) or from tissue-derived cell suspensions. Furthermore, by virtue of its high-throughput format, this method is well suited for large epidemiological surveys.
Expression of immunologically relevant endothelial cell activation antigens on isolated central neurvous system microvessels from patients with multiple sclerosis (1994)

Activation of the vascular endothelium is thought to be an important facet of inflammation, thrombosis, and vasculitis. Activated endothelial cells express a number of immunologically relevant surface markers not expressed by normal endothelial cells. Many of these surface antigens are thought to augment adhesion reactions and migration. Our results show that endothelial activation may play a central role in the pathogenesis of multiple sclerosis (MS). Normal human central nervous system microvessels isolated from autopsy material do not express endothelial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase plasminogen activator receptor. Control microvessels exhibit no major histocompatibility complex (MHC) class II antigen. MS microvessels express significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin than did microvessels from periplaque zones. However, MHC class II antigens and urokinase plasminogen activator receptor were increased in areas exhibiting little to no evidence of leukocyte infiltration. When microvessels were examined for dual expression of activation markers, we found that in periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and 43% of microvessels coexpressed HLA-DR and ICAM-1.