gebhart/patrepeval huggingface dataset:
Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. (1981)

Optimal conditions were established for the adoptive transfer of experimental allergic encephalomyelitis (EAE) in SJL/J mice. Lymph node cells from SJL/J mice primed in vivo with myelin basic protein (BP) were incubated in vitro with BP. These cells proliferated specifically to BP and when transferred at the optimal conditions into syngeneic mice induced EAE in 100% of the recipients. The in vitro proliferative response to BP was dependent on the presence of Lyt 1+ 2- T lymphocytes. Furthermore, when the activated LNC were treated before transfer with anti-Thy 1 or anti-Lyt 1 antibody and C, neither clinical nor histologic signs were observed in the recipients, whereas treatment with anti-Lyt 2 antibody and C had no effect. These results indicated that Lyt 1+ 2- T cells are responsible for the transfer of EAE.
Mutational Analysis of Avidity and Fine Specificity of Anti-Levan Antibodies (1999)

Using the polyfructose, bacterial levan, as a model polysaccharide, we analyzed how V regions affect binding in anti-polysaccharide mAbs. Previously, panels of mAb were constructed from bacterial levan-immunized BALB/c and CBA/Ca mice. The BALB/c mAb were mostly germline VHJ606:Vkappa11, and a subset contained presumed somatic mutations in the complementarity-determining regions (CDRs) that correlated with increases in avidity for the beta(2-->1) inulin linkage of levan. The CBA/Ca mAb were more heterogeneous in V gene usage, but a subset of inulin-nonreactive mAb were VHJ606:Vlambda and had VH sequence differences in the CDRs from the VHJ606 regions of the BALB/c mAb. In this report, VHJ606 Abs containing various combinations of specifically mutated H and L chains were produced by engineered transfectants and tested for inulin avidity and levan binding. Two presumed somatic mutations seen in CDRs of the BALB/c hybridomas were shown to directly cause marked increases in avidity for inulin (VH N53H, 9-fold; VL N53I, 20-fold; together, 46-fold) but not for beta(2-->6) levan. Exchange of either positions 50 or 53 in VH or the H3 loop between the BALB/c and CBA/Ca mAb resulted in either fine specificity shift or total loss of bacterial levan binding. Three-dimensional models of the V regions suggested that residues that affect binding to inulin alone are near the edge of the CDR surface, while residues involved with binding both forms of levan and affecting fine specificity are in the VH:VL junctional area.
An Elisa assay for avian serum butyrylcholinesterase: A biomarker for organophosphates (1994)

Abstract A competitive enzyme linked immunosorbent assay (ELISA) for the quantification of butyrylcholinesterase (BChE) (EC 3 1 1 8) substance concentration in avian serum samples is described The assay is based on polyclonal (rabbit) anti pigeon BChE coupled with biotin The binding of the biotinylated antibody to immobilized antigen is competitively inhibited by an added standard or test antigen, and the amount of label bound antibody is inversely related to the concentration of antigen The assay yields positive reactions with as little as 0 15 ng/ml of antigen The assay was employed to investigate changes in the quantities of BChE in avian serum, following exposure to organophosphorus insecticides, which are not measured by the standard bioassay of this enzyme The applicability of the assay to metabolic and toxicological studies is demonstrated, and the de termination of the specific activity of BChE is recommended as a rational diagnostic tool after measurement of both activity and concentration of the enzyme
Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing–remitting MS (2007)

Glatiramer acetate (GA) 40 mg was safe and well tolerated. The overall efficacy results suggested that a 40-mg dose of GA may be more effective than the currently approved 20-mg daily dose in reducing MRI activity and clinical relapses.
High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy (2005)

Mutations in the kinase domain (KD) of BCR-ABL are the leading cause of acquired imatinib resistance. In some cases, identical mutations were detected at relapse and in pretherapeutic specimens, consistent with selection of resistant clones in the presence of drug. However, the incidence of KD mutations in imatinibnaive patients, irrespective of response to therapy, is unknown. We studied mutation frequency in 66 patients with chronic myelogenous leukemia (CML), using cDNA sequencing and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) assays for 8 common mutations. Thirteen patients were positive by ASO-PCR only, 1 by ASO-PCR and sequencing, and 1 by sequencing only (overall frequency, 22.7%). T315I was most frequent (12% of patients). Eleven of the 14 patients with positive ASO-PCR had follow-up samples available for sequencing. Wild-type sequence was detected in 6 of 11, 2 different mutations in 1 of 11, and identical mutations in 4 of 11 patients, 2 of whom had achieved major cytogenetic response. In multivariate analysis mutation detection was associated with clonal cytogenetic evolution, exposure to 6-Thioguanine, and a low platelet count, but not with response to imatinib, event-free survival, and overall survival. KD mutants present at low levels do not invariably lead to relapse, and additional factors are required to induce a fully drug-resistant phenotype.
THE SO-CALLED ACYLANTHRANILS (3,1,4-BENZOXAZONES). I. PREPARATION; REACTIONS WITH WATER, AMMONIA, AND ANILINE; STRUCTURE1 (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE SO-CALLED ACYLANTHRANILS (3,1,4-BENZOXAZONES). I. PREPARATION; REACTIONS WITH WATER, AMMONIA, AND ANILINE; STRUCTURE1DAVID T. ZENTMYER and E. C. WAGNERCite this: J. Org. Chem. 1949, 14, 6, 967–981Publication Date (Print):November 1, 1949Publication History Published online1 May 2002Published inissue 1 November 1949https://pubs.acs.org/doi/10.1021/jo01158a006https://doi.org/10.1021/jo01158a006research-articleACS PublicationsRequest reuse permissionsArticle Views782Altmetric-Citations107LEARN 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
Annual Deaths Attributable to Obesity in the United States (1999)

The estimated number of annual deaths attributable to obesity among US adults is approximately 280000 based on HRs from all subjects and 325000 based on HRs from only nonsmokers and never-smokers.
Chloroplast DNA transcripts are encapsidated by tobacco mosaic virus coat protein (1984)

Preparations of tobacco mosaic virus contain pseudovirions, particles resembling virions but containing host rather than viral RNA. The encapsidated host RNA was found to be composed of discrete-sized species derived from a large portion of the chloroplast genome except that very little, if any, ribosomal RNA is present. Pseudovirions contain the same chloroplast DNA transcripts as those detected in extracts from uninfected leaves, although not always in the same relative amounts. Several strains of tobacco mosaic virus were tested and all were found to contain pseudovirions, with the U2 strain containing more than the others.
Retroviruses and Evolution (1986)

This discussion will deal with one of the exceptions to the grand ideas that laid the basis of all modern work in molecular biology. This will also serve as an introduction to the next two articles. Together, the three articles will cover an entire area of research.
Regional Disparities of Endocardial Atrial Activation in Paroxysmal Atrial Fibrillation (1996)

Quantitative assessment of complex electrical activity in both atria in humans shows heterogeneous temporal and spatial distribution. This may have implications for guiding catheter ablation of AFib.
ALTERNATIVE MORPHOGENETIC EVENTS IN CELL SUSPENSIONS (1966)

Two distinct types of regeneration, rhizogenesis and embryogenesis, were observed as alternative morphogenetic events in wild carrot cell suspensions. Petiole‐derived callus, grown on high‐auxin media lacking reduced nitrogen, was dispersed, passed through sieves, and the 45–75‐μ fraction was used to inoculate low‐auxin liquid media. After 2–3 weeks adventitious roots developed from endogenous primordia within large cell clumps. In contrast, liquid cultures inoculated with the same fraction, or with the fraction that passed a 45 μ pore sieve, from callus grown on media containing reduced nitrogen yielded enormous numbers of embryos. Globular proembryos were recognizable within several days of inoculation as bud‐like outgrowths from relatively few‐celled proembryogenic masses. The ontogeny of embryos from cultured cells has been compared to the ontogeny of the carrot seed embryo. These new data are discussed in the light of previous regenerative work with carrot cell cultures, current theories of causal aspects of embryogenesis in vitro, and current concepts of the forces controlling embryo development.
Renal mesangial cell cultures as a model for study of erythropoietin production. (1983)

Mesangial cells derived from isolated glomeruli of rat kidney were grown as homogeneous cell lines in culture. They released, into the culture medium, erythropoietin that had free terminal galactosyl residues and was therefore not active in vivo. The production of erythropoietin by these cells was significantly enhanced by either lowering the PO2 in the incubation atmosphere or by adding cobalt chloride to the culture medium. Therefore, mesangial cells in culture may be considered as an in vitro system in which the regulation of erythropoietin production can be studied under well-defined conditions.
Use of modified T7 DNA polymerase (sequenase version 2.0™) for oligonucleotide site-directed mutagenesis (1989)

Efficient oligonucleotide site-directed mutagenesis is critically dependent on successful primer extension from the mutagenic oligonucleotide. Modified T7 DNA polymerase (Sequenase) may be particularly suitable for this application because of its high processivity and lack of 3'-5' exonuclease activity. I describe here a procedure for oligonucleotide site-directed mutagenesis using this enzyme. This procedure was used to make a 90 bp insertion into a gene cloned into M13mpl8 with an oligonucleotide 120 bp long, for which a conventional procedure using the Klenow enzyme (1) had been unsuccessful.
Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. (1999)

Angiogenesis is essential for tumor progression and metastasis. It is mediated by the release of angiogenic factors by the tumor or host. We analyzed the expression of angiogenic factors by the prostate cancer cell line LNCaP and two derived variants, in vitro and in vivo, to determine whether metastatic cell lines express higher levels of these factors. The production of three angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin 8 (IL-8), by LNCaP and its variants, LNCaP-LN3 (highly metastatic) and LNCaP-Pro5 (slightly metastatic), was measured by ELISA. VEGF, bFGF, and IL-8 mRNA expression was determined in vitro by Northern blot analysis. VEGF mRNA expression was determined in vivo by in situ hybridization. VEGF and flk-1 protein expression and microvessel density of LNCaP cell tumors were quantified by immunohistochemistry. In vitro, VEGF production by LNCaP-LN3 (3.15+/-0.04 pg/ml/10(3) cells) was significantly higher than those of both LNCaP (2.38+/-0.34 pg/ml/10(3) cells) and LNCaP-Pro5 (1.67+/-0.37 pg/ml/10(3) cells; P = 0.049 and 0.001, respectively). None of the three cell lines produced detectable levels of bFGF or IL-8 in vitro. In vivo, LNCaP-LN3 tumors exhibited higher levels of VEGF mRNA and protein (152.2+/-28.5 and 200.5+/-28.3) and of flk-1 protein (156.5+/-20.6) and had higher microvessel density (16.4+/-4.2) than either LNCaP tumors (89+/-17.5, 173.3+/-23.0, 124.6+/-21.6, and 12.4+/-3.5, respectively) or LNCaP-Pro5 tumors (63+/-14.7, 141.2+/-38.1, 126.1+/-20, and 5.8+/-2.2, respectively). In conclusion, metastatic human prostate cancer cells exhibited enhanced VEGF production and tumor vascularity compared with prostate cancer cells of lower metastatic potential. Thus, VEGF may play an important role in prostate cancer metastasis.
A policy framework for integrated and differentiated services in the Internet (1999)

We examine the issues that arise in the definition, deployment, and management of policies related to QoS in an IP network. The article provides an overview of requirements for QoS policies, alternative policy architectures that can be deployed in a network, different protocols that can be used to exchange policy information, and exchange of policy information among different administrative domains. We discuss current issues being examined in IETF and other standards bodies, as well as issues explored in ongoing policy-related research at different universities and research laboratories.
Successful Treatment of Mucormycosis and Aspergillus sp. Rhinosinusitis in an Immunocompromised Patient. (1998)

Fungal rhinosinusitis is a serious infection related to immunosuppressive conditions. It is caused by common opportunistic mycoses, such as Mucor, Aspergillus sp. and Candida sp. Treatment is difficult and most of the patients with an invasive form, die. We report a case of a 13 year old boy who developed Mucor and Aspergillus sp rhinosinusitis while receiving chemotherapy for acute lymphoblastic leukemia. Even though the patient was intensely immunossupressed, early diagnoses associated with surgical debridement and effective doses of amphotericin B allowed a favorable outcome and hospital discharge.
Dominance of CD4+ lymphocytic infiltrates with disturbed effector cell characteristics in the tumor microenvironment of prostate carcinoma (2007)

In the prostate cancer microenvironment, CD4+ T lymphocytes dominated while CD8+ T cells were sparse. The lymphocytes exhibited signs of disturbed effector function. Consequently, the immune response against autologous tumor cells is likely to be inefficient in controlling tumor growth.
Axin and GSK3-β control Smad3 protein stability and modulate TGF-β signaling (2008)

The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.
Thin-film palladium and silver alloys and layers for metal-insulator-semiconductor sensors (1987)

The addition of Ag to Pd in the gate metal of a metal-insulator-semiconductor gas sensing diode can improve the performance and change the selectivity of the sensors for a variety of reactions. Data on the response of diodes with 12 different ratios of Ag to Pd in alloys and layers of Pd and Ag to hydrogen and other gases are reported. Diodes with as much as 32% Ag respond very well to H2 gas and the films are much more durable to high hydrogen exposure than pure Pd films. Improvements in the rate of response and aging behavior are found for certain Ag combinations; others give poorer performance. The presence of Ag on the surface changes the catalytic activity in some cases and examples of H2 mixed with O2 and/or NO2, propylene oxide, ethylene, and formic acid are given. Such selectivity forms the basis for miniature chemical sensor arrays which could analyze complex gas mixtures.
Combination Therapy with Methotrexate and Chloroquine in Rheumatoid Arthritis:A Multicenter Randomized Placebo-controlled Trial (1994)

To compare the efficacy of the combination therapy Methotrexate (MTX) and Chloroquine (CHLO) with MTX and Placebo (PLA) in the treatment of Rheumatoid Arthritis. A total of 82 patients with Rheumatoid Arthritis (RA), diagnosed according to the American College of Rheumatology criteria, received orally either MTX 7.5 mg/week and CHLO 250 mg/day or MTX 7.5 mg/week and PLA 1 tablet/day. Adverse effects (AE) were monitored monthly and disease activity was assessed at 0, 2, 4 and 6 months. Sixty-eight patients completed the study. All outcome measures improved significantly in both treatment groups. Patients receiving MTX/CHLO ended the study with a significantly lower joint count, greater grip strength and better functional ability the patients in the MTX/PLA group, respectively; 4.5 vs 7.5 (P < 0.05), 113.3 vs 89.1 (P < 0.05) and 0.636 vs 0.811 (P < 0.05). Mild AE were more frequently observed in the MTX/CHLO, 17 events in 15 patients, compared to 9 events in 8 patients in the MTX/PLA group (NS). These data indicate that MTX/CHLO is slightly more efficacious and toxic than is MTX/PLA in the treatment of RA.
Enzymatic Fixation of Carbon Dioxide in α-Ketoglutaric Acid (1948)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Current and novel immunosuppressive therapy for autoimmune hepatitis (2002)

Corticosteroids alone or in conjunction with azathioprine is the treatment of choice in patients with autoimmune hepatitis (AIH) and results in remission induction in over 80% of patients. Sustained response to therapy may result in substantial regression of fibrosis even in advanced cases. The outcome of rapid withdrawal of immunosuppression is disease relapse in many patients. Consequently, the use of 2 mg/kg/d of azathioprine as a sole agent to maintain remission has been widely accepted in clinical practice. Persistent severe laboratory abnormalities or histologic abnormalities such as bridging necrosis or multilobular necrosis are absolute indications for treatment based on controlled clinical trials, but debate exists as to whether all patients with AIH need treatment. Examination of liver tissue remains the best method of evaluating both treatment response and need for treatment in patients who have little biochemical activity. Alternative strategies in patients who have failed to achieve remission on "standard therapy" of corticosteroids with or without azathioprine or patients with drug toxicity include the use of cyclosporine, tacrolimus, or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease. In this review we examine current management strategies of AIH, and evaluate available data pertaining to the use of novel immunosuppressive agents in this condition.
Increased Colonization of Indwelling Medical Devices by Quorum‐Sensing Mutants ofStaphylococcus epidermidisIn Vivo (2004)

Infections with the leading nosocomial pathogen Staphylococcus epidermidis are characterized by biofilm development on indwelling medical devices. We demonstrate that the quorum-sensing regulator agr affects the biofilm development of S. epidermidis in an unexpected fashion and is likely involved in promoting biofilm detachment. An isogenic agr mutant showed increased biofilm development and colonization in a rabbit model. In addition, nonfunctional agr occurred more frequently among strains isolated from infections of joint prostheses. Lack of functionality was based on mutations, including insertion of an IS256 element. Relative to other bacterial pathogens, quorum sensing in S. epidermidis thus has a different role during biofilm development and biofilm-associated infection. Our results indicate that disabling agr likely enhances the success of S. epidermidis during infection of indwelling medical devices. The permanent elimination of quorum-sensing regulation used by S. epidermidis represents a surprising and unusual means to adapt to a certain environment and type of infection.
Pharmacological inhibition of NF-κB-inducing kinase (NIK) with small molecules for the treatment of human diseases (2021)

NIK is a key kinase required for the activation of alternative NF-κB signaling pathways. Overactivation of NIK in patients has been observed and is implicated in the pathogenesis of inflammatory diseases, B-cell malignances, and solid tumors. Over the past decade, inhibition of NIK overactivation with small molecules has been pursued as an attractive strategy for drug discovery, where numerous potent and selective NIK inhibitors with novel pharmacophores have been identified. This review summarizes the structural features and key efficacy studies of the NIK inhibitors reported, which justify the mechanism of action of such inhibitors in animal models driven by NIK overactivation. Given the strong pathological associations between overactivation of NIK and human diseases, human clinical trials of NIK inhibitors as drug candidates are eagerly awaited. Information showcased in this review article might be helpful for the discovery and clinical development of the next generation of NIK inhibitors in the near future.