gebhart/patrepeval huggingface dataset:
The role of acid phosphatases in plant phosphorus metabolism (1994)

Hydrolysis of phosphate esters is a critical process in the energy metabolism and metabolic regulation of plant cells. This review summarizes the characteristics and putative roles of plant acid phosphatase (APase). Although immunologically closely related, plant APases display remarkable heterogeneity with regards to their kinetic and molecular properties, and subcellular location. The secreted APases of roots and cell cultures are relatively non‐specific enzymes that appear to be important in the hydrolysis and mobilization of P i from extracellular phosphomonoesters for plant nutrition. Intracellular APases are undoubtedly involved in the routine utilization of P i reserves or other P i ‐containing compounds. A special class of intracellular APase exists that demonstrate a clear‐cut (but generally nonabsolute) substrate selectivity. These APases are hypothesized to have distinct metabolic functions and include: phytase, phosphoglycolate phosphatase, 3‐phosphoglycerate phosphatase, phosphoenolpyruvate phosphatase, and phosphotyrosyl‐protein phosphatase. APase expression is regulated by a variety of developmental and environmental factors. P i starvation induces de novo synthesis of extra‐ and intracellular APases in cell cultures as well as in whole plants. Recommendations are made to achieve uniformity in the analyses of the different APase isoforms normally encountered within and between different plant tissues.
Predominance of Large LDL and Reduced HDL 2 Cholesterol in Normolipidemic Men With Coronary Artery Disease (1995)

Previous studies have indicated that a predominance of small, dense LDL particles is associated with coronary artery disease (CAD) risk. In the present study we examined the LDL peak particle diameter (determined by lipid-stained 2% to 16% gradient gel electrophoresis) in 92 normolipidemic men with CAD (total cholesterol < 200 mg/dL and triglyceride < 250 mg/dL) and 92 matched healthy controls. Plasma triglyceride, LDL cholesterol, and apo B levels were similar in subjects with CAD and in control subjects, whereas subjects with CAD had decreased HDL2 cholesterol levels (mean +/- SEM, 10 +/- 0.7 compared with 15 +/- 0.7 mg/dL in control subjects; P < .0002). Mean LDL particle diameter (+/- SEM) was increased in the subjects with CAD compared with control subjects (26.8 +/- 0.08 and 26.4 +/- 0.08 nm, respectively; P < .001). The association between large LDL size and CAD was significant (P < .0001) after adjustments were made for age, body mass index, HDL cholesterol levels, and VLDL cholesterol levels. An LDL particle size distribution characterized by a predominance of the largest of three classes of LDL particles (> 26.8 nm) was more prevalent among subjects with CAD (43%) than among control subjects (25%) (P < .002). Among subjects with this LDL size profile, subjects with CAD had significantly higher (P < .05) VLDL triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower (P < .0001) HDL2 cholesterol levels than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidermal growth factor (EGF) stimulates EGF receptor synthesis. (1986)

Epidermal growth factor (EGF) binds to the extracellular domain of a specific 170,000-dalton transmembrane glycoprotein; this results in rapid removal of both ligand and receptor from the cell surface. In WB cells, a rat hepatic epithelial cell line, ligand-directed receptor internalization leads to receptor degradation. We tested whether the EGF receptor was replenished at a constitutive or enhanced rate following EGF binding by immunoprecipitating biosynthetically labeled EGF receptor from cells cultured with [35S]methionine. EGF stimulated receptor synthesis within 2 h in a dose-dependent manner; this was particularly evident when examining the nascent form of the receptor. To determine the site of EGF action, total WB cell RNA was transferred to nitrocellulose paper after electrophoresis and was hybridized to cDNA probes from both the external and cytoplasmic coding regions of the human EGF receptor. EGF increased receptor mRNA by 3-5-fold. Therefore, at least in some cells, the surface action of EGF that leads to EGF receptor degradation is counterbalanced by a positive effect on receptor synthesis.
Cascading Glia Reactions: a Common Pathomechanism and Its Differentiated Control by Cyclic Nucleotide Signaling (2000)

A pathological glia activation, stimulated by inflammatory proteins, beta-amyloid, or brain ischemia, is discussed as a common pathogenic factor for progressive nerve cell damage in vascular and Alzheimer dementia. A critical point seems to be reached, if the cytokine-controlled microglial upregulation causes a secondary activation of astrocytes which loose the negative feedback control, are forced to give up their physiological buffering function, and may add to neuronal damage by the release of nitric oxide (NO) and by promoting toxic beta-amyloid formation. A strengthening of the cyclic adenosine-5',3'-monophosphate (cAMP) signaling exerted a differential inhibition of the stimulatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) released from cultured rat microglia, but maintained the negative feedback signal IL-6; cAMP inhibited also the release of free oxygen radicals (OR) but not of NO. Reinforcement of the NO-induced cyclic guanosine monophosphate (cGMP) increase by blockade of the phosphodiesterase (PDE) subtype-5 with propentofylline counterbalanced the toxic NO action that causes with OR neuronal damage by peroxynitrate formation. In rat cultured astrocytes, a prolonged cAMP elevation favored cell differentiation, the expression of a mature ion channel patter, and an improvement of the extracellular glutamate uptake. Cyclic AMP signaling could be strengthened by PDE blockade and by raising extracellular adenosine, which stimulates A2 receptor-mediated cAMP synthesis. Via an A1 receptor-mediated effect, elevated adenosine was found to overcome a deficient intracellular calcium mobilization resulting from an impaired muscarinic signaling at pathologically decreased acetylcholine concentrations. We suggest that pharmaca, which elevate extracellular adenosine and/or block the degradation of cyclic nucleotides, may be used to counteract glia-related neuronal damage in dementing processes.
Delayed-type hypersensitivity, contact sensitivity, and phytohemagglutinin skin-test responses of heat- and cold-stressed calves (1982)

Three-week-old Holstein bull calves were used to investigate the effect of a 2-week chronic heat (35 C) or cold (-5 C) exposure on delayed-type hypersensitivity (DTH) reactions to purified protein derivative after sensitization with heat-killed Mycobacterium tuberculosis, contact sensitivity (CS) reactions to 1-fluoro-2,4-dinitrobenzene, and phytohemagglutinin (PHA) skin tests. Heat exposure reduced expression of DTH reactions by 42% and CS reactions by 38% at 24 hours after elicitation of the responses. The PHA-induced skin tests were not affected after 1 week of heat exposure, but this reaction was reduced by 20% after 2 weeks of heat exposure. The immune response of calves exposed to cold air temperatures was more complex. Cold exposure suppressed CS reactions by 39% at the end of both the 1st and 2nd weeks. The PHA response was reduced by 39% after 2 weeks of cold exposure. The DTH response depended on duration of cold exposure. The DTH reaction was increased by 42% after 1 week, but was reduced by 14% after 2 weeks. These data are consistent with the hypothesis that environmental stressors alter host resistance by affecting the immune system. Furthermore, these stress-induced changes in immune events depend on the type of immune response, the nature of the environmental stressor, and the length of time that calves are exposed to the stressor.
DNA Vaccines – An Overview (2005)

This chapter contains sections titled: Rationale for DNA Vaccines Preclinical Proof of Concept Clinical Trials Second-Generation Vaccines Conclusions References
Absence of Programmed Death Receptor 1 Alters Thymic Development and Enhances Generation of CD4/CD8 Double-Negative TCR-Transgenic T Cells (2003)

Programmed death receptor 1 (PD-1) is expressed on thymocytes in addition to activated lymphocyte cells. Its ligation is thought to negatively regulate T cell activation, and PD-1(-/-) mice develop autoimmunity. To study the role of PD-1 on the development and function of a monoclonal CD8(+) T cell population, 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice were generated. Unexpectedly, approximately 30% of peripheral T cells in these mice were CD4/CD8 double negative (DN). Although the DN cells were not activated by Ag-expressing APCs, they functioned normally in response to anti-CD3/anti-CD28. These cells had a naive surface phenotype and lacked expression of NK1.1, B220, and gammadelta TCR; and the majority did not up-regulate CD8alphaalpha expression upon activation, arguing that they are not predominantly diverted gammadelta-lineage cells. The thymus was studied in detail to infer the mechanism of generation of DN peripheral T cells. Total thymus cellularity was reduced in 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice, and a relative increase in DN cells and decrease in double-positive (DP) cells were observed. Increased annexin V(+) cells among the DP population argued for augmented negative selection in PD-1(-/-) mice. In addition, an increased fraction of the DN thymocytes was HSA negative, suggesting that they had undergone positive selection. This possibility was supported by decreased emergence of DN PD-1(-/-) 2C cells in H-2(k) bone marrow chimera recipients. Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells.
Simple and Efficient Algorithm for Approximate Dictionary Matching (2010)

This paper presents a simple and efficient algorithm for approximate dictionary matching designed for similarity measures such as cosine, Dice, Jaccard, and overlap coefficients. We propose this algorithm, called CPMerge, for the τ-overlap join of inverted lists. First we show that this task is solvable exactly by a τ-overlap join. Given inverted lists retrieved for a query, the algorithm collects fewer candidate strings and prunes unlikely candidates to efficiently find strings that satisfy the constraint of the τ-overlap join. We conducted experiments of approximate dictionary matching on three large-scale datasets that include person names, biomedical names, and general English words. The algorithm exhibited scalable performance on the datasets. For example, it retrieved strings in 1.1 ms from the string collection of Google Web1T unigrams (with cosine similarity and threshold 0.7). 1
Stiff subcircuit islands of diamondlike carbon for stretchable electronics (2006)

Stretchable electronics on elastomeric substrates requires fragile and brittle device materials to be placed on stiff, mechanical distinct subcircuit islands. We deposited a diamondlike carbon (DLC) film at room temperature on a silicone substrate by pulsed laser ablation, and patterned the film into an array of 200×200μm2 islands. When the substrate was uniaxially stretched to a strain of 25%, the islands remained adherent to the substrate and only deformed by ∼5%, while the exposed substrate stretched by more than 30%. A row of 11 DLC islands interconnected with gold stretchable metallization maintained end-to-end electrical conduction during a mechanical cycle to 20% tensile strain. This demonstration of electrically interconnected stiff islands on silicone illustrates two important steps toward fully integrated, elastically stretchable electronics.
ChemInform Abstract: AN APPROACH TO THE SYNTHESIS OF (2)BENZOPYRANO(3,4‐C)PYRROLES; ALTERNATIVE DOPAMINERGIC MOLECULES (1982)

Abstract Die aus den Vorstufen (I) bzw. (IIa) erhältliche Säure (IIb) wird in 6 Schritten in den Aldehyd (IIc) übergeführt.
Cytokines in Inflammatory Bowel Disease (1998)

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 (2017)

Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.
Famciclovir therapy for recurrent hepatitis B virus infection after liver transplantation (1996)

Abstract Between November 1993 and June 1995 18 patients received oral famciclovir (3 times 500 mg) for treatment of hepatitis B virus (HBV) reinfection after liver transplantation. Reinfection was defined as the reoccurrence of HBsAg in the serum. In the first 15 patients, famciclovir therapy was initiated after clinical signs of graft hepatitis, whereas the last 3 patients received treatment immediately after HBV-DNA was detected. Famciclovir was well-tolerated in all patients. HBV-DNA values were decreased to undetectable levels in 8 out of 18 patients. Clinical status improved in 7 patients, whereas 5 patients remained unchanged and 6 patients progressed to deteriorating graft function and death. When famciclovir was initiated early after reinfection, a response rate of approximately 66 % was observed. Late onset of therapy in patients with fulminant hepatitis generally failed to provide any clinical benefit.
Next-generation sequencing: a transformative tool for vaccinology (2009)

Next-generation sequencing (NGS) has revolutionized the fields of basic and clinical research in the 5 years since its introduction to the scientific community. Current NGS platforms on the market such as Roche 454 (Roche, CT, USA), Genome Analyzer (Illumina/Solexa, CA, USA), SOLiD (Applied Biosystems [ABI], CA, USA) and Heliscope (Helicos Biosciences, MA, USA) share one common attribute: highly parallel sequencing of DNA molecules to generate sequence outputs on an order of magnitude of 0.5 to greater than 40 Gb per sequencing run, thus enabling researchers to design experiments that were previously beyond the realms of feasibility and affordability The genotypic information obtained using these highthroughput systems allows the in-depth understanding of genotype-phenotype associations, critical to the development of the field of personalized medicine.
Factors involved in nuclear reprogramming during early development in the rabbit (1995)

Mechanisms of nuclear reprogramming and assessment of potential malfunctions that could be deleterious for development were evaluated in rabbit zygotes, parthenotes, and nuclear transfer embryos by analysis of DNA replication, nucleolar fibrillarin label, and localization of nuclear material reactive to the MPM-2 antibody. Nuclear transfer embryos were derived from G1/early S-phase donor nuclei and MII oocytes. In nuclear transfer embryos, DNA rereplication was likely to have occurred because label was incorporated, possibly in the centromeric regions of the chromosomes, prior to premature chromosome condensation and again following pronuclear formation. In parthenotes, DNA replication began very late in the cell cycle, which may be due to deficiencies in the artificial activation stimulus. The presence of fibrillarin label in the nucleolus was used as an indication of nucleolar transcriptional activity. Fibrillarin label was absent in embryos of all types up to the 16-32-cell stage. Although fibrillarin reappeared in nuclear transfer and parthenote embryos at the appropriate stage, not all blastomeres showed label indicating impaired development in these embryos. Labelling of phosphorylated epitopes by MPM-2 antibody showed a change in pattern of labelling during early development. Early cleavage stage embryos did not exhibit labelling over the spindle poles as did blastomeres from 32-cell embryos and tissue culture cells. All cell types exhibited labelling during interphase as dots located primarily over the nucleus in blastomeres from 32-cell embryos and in tissue culture cells, together with cytoplasmic label in embryos at early cleavage stages. Nuclear transplant embryos had a normal pattern of MPM-2 label. In contrast, the appearance of MPM-2 label in parthenotes depended on the type of calcium stimulation. These results demonstrate defects in DNA synthesis, nucleolar activity, and specific phosphorylation events, likely resulting from an improper activation stimulus and chromosome condensation in the transplanted nucleus.
Lipoprotein Physiology in Nondiabetic and Diabetic States: Relationship to Atherogenesis (1991)

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer (2006)

Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed.
Role of Regulatory Subunits and Protein Kinase Inhibitor (PKI) in Determining Nuclear Localization and Activity of the Catalytic Subunit of Protein Kinase A (1999)

Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.
Immunotherapy with chimeric antigen receptors for multiple myeloma. (2014)

Chimeric antigen receptors (CARs) are synthetic transmembrane proteins that are used to redirect autologous T cells with a new specificity for antigens on the surface of cancer cells. Impressive results from early phase clinical trials of anti-CD19 CARs for B cell malignancies have generated great enthusiasm for developing this approach for other diseases, particularly hematologic malignancies. Here we review efforts to develop CARs for the treatment of multiple myeloma. Clinical trials are underway investigating CARs against Kappa light chain, CD138, and Lewis Y antigen. CARs against BCMA, CS1, and CD38 are in pre-clinical testing. While initial clinical trials of novel CARs will focus on relapsed/refractory disease, CARs will also likely be studied as a consolidation strategy after response to first-line therapy or in conjunction with autologous hematopoietic stem cell transplantation.
Instant messaging in teen life (2002)

Instant Messaging (IM) is being widely adopted by teenagers. In a study of 16 teenage IM users, we explore IM as an emerging feature of teen life, focusing our questions on its support of interpersonal communication and its role and salience in everyday life. We qualitatively describe the teens' IM use interpersonally, as well as its place in the domestic ecology. We also identify technology adoption conditions and discuss behaviors around privacy management. In this initial investigation, we found differences in the nature of use between high school and college teens, differences we propose are accounted for by teens' degree of autonomy as a function of domestic and scholastic obligations, the development of independent work practices, Internet connectivity access, and even transportation access. Moreover, while teen IM use is in part characterized as an optimizing choice between multiple communications media, practice is also tied to concerns around peer pressure, peer group membership and creating additional opportunities to socialize.