gebhart/patrepeval huggingface dataset:
Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study (1991)

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m<sup>2</sup>orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4<sup>+</sup>cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)—defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to<i>Pneumocystis carinii</i>pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection. (<i>JAMA</i>. 1991;265:1538-1544)
Digital Fetal Aneuploidy Diagnosis by Next-Generation Sequencing (2009)

Since the identification of fetal lymphocytes in maternal blood in 1969, investigators have endeavored to develop genetics-based noninvasive prenatal diagnostics (NIPD)1 (1). A robust noninvasive approach would augment or potentially supplant amniocentesis and chorionic villus sampling, which, although gold standards, carry a risk of fetal loss. Despite considerable efforts, the use of fetal cells for NIPD has never reached clinical implementation because of their paucity (on the order of a few cells per milliliter of maternal blood) and concerns of fetal cell persistence in the maternal circulation between pregnancies (2). A new avenue was opened in 1997 by the discovery of circulating cell-free fetal DNA in maternal blood (3). Cell-free fetal DNA constitutes between 5% and 10% of the total DNA in maternal plasma and increases during gestation. It rapidly clears from the circulation postpartum, a feature that enhances its attractiveness as a per-pregnancy–specific analyte. Several clinical applications based on the analysis of cell-free fetal DNA have been developed. These assays include determining fetal Rh D status in Rh D-negative women (4), sex in sex-linked disorders (3)(5), and detection of paternally inherited autosomal recessive and dominant mutations (6). In the context of these successes, however, there remains the outstanding challenge of the use of cell-free fetal DNA for the detection of chromosomal aneuploidy, in particular trisomies 21, 18, and 13.

A cell-free fetal DNA–based approach for chromosomal aneuploidy must overcome several technical hurdles. By virtue of being cell free, fetal DNA in the maternal plasma cannot be easily analyzed by traditional visualization methods such as fluorescence in situ hybridization. The high “background” of maternal DNA (cell free or from residual cells) further complicates analysis by diluting the fetal genetic information. To address these issues, investigators have worked to identify fetal-specific molecular markers. The origin of circulating cell-free …
Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia (2013)

Patients with chronic myeloid leukemia develop resistance to both first-generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD mutations that confer resistance to TKIs have been identified, and the T315I mutant has proven particularly difficult to target. This review summarizes the prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in patients with chronic myeloid leukemia who are treated with current TKIs and provides an overview of recent treatment guidelines and future trends for the detection of mutations.
Quantitative relationship between functionally active telomerase and major telomerase components (hTERT and hTR) in acute leukaemia cells (2005)

Functionally active telomerase is affected at various steps including transcriptional and post-transcriptional levels of major telomerase components (hTR and human telomerase reverse transcriptase (hTERT)). We therefore developed a rapid and sensitive method to quantify hTERT and its splicing variants as well as the hTR by a Taqman real-time reverse transcriptase-polymerase chain reaction to determine whether their altered expression may contribute to telomere attrition in vivo or not. Fresh leukaemia cells obtained from 38 consecutive patients were used in this study. The enzymatic level of telomerase activity measured by TRAP assay was generally associated with the copy numbers of full-length hTERT+alpha+beta mRNA (P=0.0024), but did not correlate with hTR expression (P=0.6753). In spite of high copy numbers of full-length hTERT mRNA, telomerase activity was low in some cases correlating with low copy numbers of hTR, raising the possibility that alteration of the hTR : hTERT ratio may affect functionally active telomerase activity in vivo. The spliced nonactive hTERT mRNA tends to be lower in patients with high telomerase activity, suggesting that this epiphenomenon may play some role in telomerase regulation. An understanding of the complexities of telomerase gene regulation in biologically heterogeneous leukaemia cells may offer new therapeutic approaches to the treatment of acute leukaemia.
Tumor Necrosis Factor and Interleukin-6 Activity and Endotoxin Concentration in Peritoneal Fluid and Blood of Horses with Acute Abdominal Disease (1999)

Abstarct The purpose of this study was to evaluate the diagnostic and prognostic significance of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) activities and endotoxin concentration in blood and peritoneal fluid of 155 adult horses with acute abdominal disease (colic). Samples also were obtained from 20 healthy adult horses. Blood and peritoneal fluid supernatant TNF and IL-6 activities and endotoxin concentration were significantly greater in horses with colic, compared with healthy horses. In horses with colic, the peritoneal fluid endotoxin concentration and TNF and IL-6 activities were significantly greater than those in blood. Within the colic group, peritoneal fluid IL-6 activity was the analyte that was most frequently increased. Blood and peritoneal fluid supernatant TNF and IL-6 activities were significantly greater when endotoxin was detected in the same sample. Blood and peritoneal fluid IL-6 activity was significantly greater in horses with inflammatory or strangulating lesions, compared with horses having nonstrangulating or noninflammatory lesions. Compared with all other data categories, diagnostic accuracy for nonsurvival was greatest (80%) when blood IL-6 activity exceeded 60 units/mL. The results of this study indicate that endotoxin was present in the peritoneal cavity of at least one third of horses with any acute disease of the abdomen. In horses presented for colic, blood or peritoneal fluid IL-6 activity was more useful than either TNF activity or endotoxin concentration for distinguishing lesion type. Although diagnostic accuracy for the prediction of nonsurvival was good for all of the analytes, negative values were more useful in the prediction of a favorable outcome than were abnormally increased values in the prediction of mortality.
Interfaces for staying in the flow (2004)

Psychologists have studied optimal human experience for many years, often called in the Through years of study, the basic characteristics of flow have been identified. This paper reviews the literature, and interprets the characteristics of flow within the context of interface design with the goal of understanding what kinds of interfaces are most conducive to supporting users being in the flow. Several examples to demonstrate the connection to flow are given.
Formalin-Fixed Paraffin-Embedded Tissues (2011)

Presenting an area of research that intersects with and integrates diverse disciplines, including genomics, epigenetics, proteomics, and cellular biology, among others, Formalin-Fixed Paraffin-Embedde
Lentivirus-Mediated Transduction of Islet Grafts with Interleukin 4 Results in Sustained Gene Expression and Protection from Insulitis (1998)

Autoimmune destruction of islets in the pancreas leads to the development of insulin-dependent diabetes mellitus (IDDM). Replacement of insulin-producing tissue by transplantation of islets provides a cure to disease but requires immunosuppression or a means of controlling anti-graft immune responses. To promote islet survival we have utilized a local approach by expressing immunoregulatory molecules in islet grafts. The results presented here show that the human immunodeficiency virus (HIV)-based lentiviral vector is capable of stably transducing whole islets. Foreign reporter gene expression was observed both in vitro and in vivo 30 days after transplantation. Grafts containing insulin-positive beta-islet cells expressing foreign protein indicate that transduction does not interfere with glucose regulation. The absence of inflammatory infiltrates in grafts suggests that transduction does not activate the immune system. When islets transduced with an HIV vector expressing IL-4 were transplanted into diabetes-prone mice, animals were protected from autoimmune insulitis and islet destruction. As demonstrated by proliferative and cytokine analysis, protection was consistent with a switching of islet-antigen-specific T cell responses toward a Th2 phenotype. These results suggest that HIV-based lentivirus vectors can efficiently transduce islet cells with genes encoding potentially therapeutic molecules, for possibly managing diabetes.
ACB-PCR Quantification of Somatic Oncomutation (2014)

Allele-specific competitive blocker-polymerase chain reaction (ACB-PCR) is a sensitive approach for the selective amplification of an allele. Using the ACB-PCR technique, hotspot point mutations in oncogenes and tumor-suppressor genes (oncomutations) are being developed as quantitative biomarkers of cancer risk. ACB-PCR employs a mutant specific primer (with a 3'-penultimate mismatch relative to the mutant DNA sequence, but a double 3'-terminal mismatch relative to the wild-type DNA sequence) to selectively amplify rare mutant DNA molecules. A blocker primer (having a non-extendable 3'-end and with a 3'-penultimate mismatch relative to the wild-type DNA sequence, but a double 3'-terminal mismatch relative to the mutant DNA sequence) is included in ACB-PCR to selectively repress amplification from the abundant wild-type molecules. Consequently, ACB-PCR is capable of quantifying the level of a single basepair substitution mutation in a DNA population when present at a mutant:wild type ratio of 10(-5) or greater. Quantification of rare mutant alleles is achieved by parallel analysis of unknown samples and mutant fraction (MF) standards (defined mixtures of mutant and wild-type DNA sequences). The ability to quantify specific mutations with known association to cancer has several important applications, including evaluating the carcinogenic potential of chemical exposures in rodent models and in the diagnosis and treatment of cancer. This chapter provides a step-by-step description of the ACB-PCR methodology as it has been used to measure human KRAS codon 12 GGT to GAT mutation.
Quantitative structure—activity studies of insect growth regulators. XI. Stimulation and inhibition of N‐acetylglucosamine incorporation in a cultured integument system by substituted N‐tert‐butyl‐N,N′‐dibenzoylhydrazines (1995)

Abstract The ability to stimulate N ‐acetylglucosamine (GluNAc) incorporation in‐vitro of a number of N ‐ tert ‐butyl‐ N , N ′‐dibenzoylhydrazines having various substituents on both phenyl rings was measured in cultured integument excised from the rice stem borer ( Chilo suppressalis Walker). The relationship between in‐vitro and larvicidal potency was approximately linear. The substituent effects on variations in the potency were similar between in‐vitro and larvicidal activities. An inhibitor of oxidative detoxication, piperonyl butoxide, had no synergistic effects on the in‐vitro potency. The ability of some dibenzoylhydrazines to inhibit GluNAc incorporation at exposure periods longer than the optimum for stimulation was also measured in a similar cultured integument system. The relationship between the inhibitory and stimulatory potency indices was linear, indicating that the larvicidal activity of dibenzoylhydrazines is closely related to its ability to stimulate as well as to inhibit GluNAc incorporation into the larval cuticle.
Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection (2014)

Respiratory syncytial virus (RSV) infection accounts for approximately 64 million cases of respiratory disease and 200,000 deaths worldwide each year, yet no broadly effective prophylactic or treatment regimen is available. RSV deploys paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that exhibit stabilized α-helical structure and striking proteolytic resistance. Pretreatment with double-stapled RSV peptides that specifically bound to the RSV fusion bundle inhibited infection by both laboratory and clinical RSV isolates in cells and murine infection models. Intranasal delivery of a lead double-stapled RSV peptide effectively prevented viral infection of the nares. A chitosan-based nanoparticle preparation markedly enhanced pulmonary delivery, further preventing progression of RSV infection to the lung. Thus, our results provide a strategy for inhibiting RSV infection by mucosal and endotracheal delivery of double-stapled RSV fusion peptides.
ChemInform Abstract: Chemical Synthesis of DNA and DNA Analogues (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Androgen metabolism in the human prostate gland (1975)

1. Testosterone 5alpha-reductase, the enzyme responsible for the production of dihydrotestosterone, was partially characterised in human benign hyperplastic prostatic tissue removeo at surpery. Biochemical experiments were carried out with fresh tissue or with tissue frozen in liquid nitrogen and stored for a limited period at -70
Single pulse Bragg gratings written during fibre drawing (1993)

For the first time the production of Bragg fibre gratings written by single excimer laser pulses as the fibre is being drawn is demonstrated. Reflectivities approaching 100% have been obtained, demonstrating the feasibility of online mass production.
Insulator‐based dielectrophoresis for the selective concentration and separation of live bacteria in water (2004)

Insulator-based dielectrophoresis (iDEP) was utilized to separate and concentrate selectively mixtures of two species of live bacteria simultaneously. Four species of bacteria were studied: the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis, B. cereus, and B. megaterium. Under an applied direct current (DC) electric field all the bacterial species exhibited negative dielectrophoretic behavior. The dielectrophoretic separations were carried out in a glass microchannel containing an array of insulating posts. The insulating posts in the microchannel produced nonuniformities in the electric field applied along the channel. Mixtures of two species of bacteria were introduced into the microchannel and the electric field was applied. The bacterial species exhibited different dielectrophoretic mobilities under the influence of the nonuniform field. From these experiments a trapping order was established with E. coli trapping at the weakest applied electric field, while the Bacillus species were trapped at different characteristic threshold fields. At stronger applied electric fields, the two different species of bacteria in the microchannel were dielectrophoretically trapped into two spatially distinct bands. The results showed that iDEP has the potential to selectively concentrate and separate different species of bacteria.
Simplified support vector decision rules (1996)

Pleural effusion caused by drug is an uncommon event in clinical practice. Etoricoxib induced pleural effusion is an extremely rare. We describe a patient with pleural effusion as an adverse drug reaction of etoricoxib.
A 20nm 1.8V 8Gb PRAM with 40MB/s program bandwidth (2012)

Phase-change random access memory (PRAM) is considered as one of the most promising candidates for future memories because of its good scalability and cost-effectiveness [1]. Besides implementations with standard interfaces like NOR flash or LPDDR2-NVM, application-oriented approaches using PRAM as main-memory or storage-class memory have been researched [2-3]. These studies suggest that noticeable merits can be achieved by using PRAM in improving power consumption, system cost, etc. However, relatively low chip density and insufficient write bandwidth of PRAMs are obstacles to better system performance. In this paper, we present an 8Gb PRAM with 40MB/s write bandwidth featuring 8Mb sub-array core architecture with 20nm diode-switched PRAM cells [4]. When an external high voltage is applied, the write bandwidth can be extended as high as 133MB/s.
ChemInform Abstract: Novel anti‐β‐Functionalized γ,δ‐Unsaturated Amino Acids via a Thio‐Claisen Rearrangement. (2010)

Abstract A significantly improved approach to novel title compounds is developed.
Review: S-adenosylmethionine treats osteoarthritis as effectively as nonsteroidal anti-inflammatory drugs with fewer adverse effects (2003)

TherapeuticsJanuary 1, 2003Review: S-adenosylmethionine treats osteoarthritis as effectively as nonsteroidal anti-inflammatory drugs with fewer adverse effectsOliver Sander, MDOliver Sander, MDHeinrich-Heine University, Duesseldorf, Germany (O.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2003-138-1-021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationSoeken KL, Lee W-L, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51:425-30. https://pubmed.ncbi.nlm.nih.gov/12019049References1 Fife RS. Prevalence of osteoarthritis in different populations. In: Klippel JH, Weyand CM, Wortmann R, eds. Primer on the rheumatic diseases, 11th ed. Atlanta: Arthritis Foundation; 1997. [PMID: 9709517] Google Scholar2 Tramer MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain. 2000;85:169-82. [PMID: 10692616] Google Scholar3 Courtney P, Doherty M. Key questions concerning paracetamol and NSAIDs for osteoarthritis. Ann Rheum Dis. 2002;61:767-73. [PMID: 12176799] Google Scholar4 American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43:1905-15. [PMID: 11014340] Google Scholar Author, Article, and Disclosure InformationAffiliations: Heinrich-Heine University, Duesseldorf, Germany (O.S.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails January 1, 2003Volume 138, Issue 1Page: 21 ePublished: 9 March 2020 Issue Published: January 1, 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Crystal structure of glucoamylase from Aspergillus awamori var. X100 to 2.2-A resolution. (1992)

The crystal structure of a catalytically active fragment of glucoamylase-I from Aspergillus awamori var. X100 has been determined to a resolution of 2.2 A. Twelve of its 13 alpha-helices are arranged into an "alpha/alpha-barrel." An inner core of six mutually parallel alpha-helices are connected to each other through a peripheral set of six alpha-helices. The peripheral helices are parallel to each other, but approximately antiparallel to the inner core of alpha-helices. The putative active site lies in the packing void of the inner set of helices. The last 30 residues of the enzyme comprise a separate domain containing 10 sites of O-glycosylation. Each instance of O-glycosylation involves a serine or threonine side chain linked to the alpha-anomer of a single mannosyl residue. The O-glycosylated domain is in an extended conformation, wrapping around the "waist" of the alpha/alpha-barrel. Two additional sites of N-glycosylation contribute well ordered glycosyl chains that lie in proximity to the belt of O-glycosylation. The model developed for glucoamylase is a rare and valuable structural example of a glycoprotein and an exo-acting amylolytic enzyme.
Tumor Necrosis Factor-α-induced Insulin Resistance in 3T3-L1 Adipocytes Is Accompanied by a Loss of Insulin Receptor Substrate-1 and GLUT4 Expression without a Loss of Insulin Receptor-mediated Signal Transduction (1997)

A number of studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is associated with profound insulin resistance in adipocytes and may also play a critical role in the insulin resistance of obesity and non-insulin-dependent diabetes mellitus. Reports on the mechanism of TNF-alpha action have been somewhat contradictory. GLUT4 down-regulation has been implicated as a possible cause of insulin resistance as has been the reduced kinase function of the insulin receptor. Here we examine the effects of tumor necrosis factor on the protein components thought to be involved in insulin-stimulated glucose transport in adipocytes, namely the insulin receptor, its major substrate IRS-1, and the insulin responsive glucose transporter GLUT4. Prolonged exposure (72-96 h) of 3T3-L1 adipocytes to TNF-alpha causes a substantial reduction (>80%) in IRS-1 and GLUT4 mRNA and protein as well as a lesser reduction (>50%) in the amount of the insulin receptor. Nevertheless, the remaining proteins appear to be biochemically indistinguishable from those in untreated adipocytes. Both the insulin receptor and IRS-1 are tyrosine-phosphorylated to the same extent in response to acute insulin stimulation following cellular TNF-alpha exposure. Furthermore, the ability of the insulin receptor to phosphorylate exogenous substrate in the test tube is also normal following its isolation from TNF-alpha-treated cells. These results are confirmed by the reduced but obvious level of insulin-dependent glucose transport and GLUT4 translocation observed in TNF-alpha-treated adipocytes. We conclude that the insulin resistance of glucose transport in 3T3-L1 adipocytes exposed to TNF-alpha for 72-96 h results from a reduced amount in requisite proteins involved in insulin action. These results are consistent with earlier studies indicating that TNF-alpha reduces the transcriptional activity of the GLUT4 gene in murine adipocytes, and reduced mRNA transcription of a number of relevant genes may be the general mechanism by which TNF-alpha causes insulin resistance in adipocytes.