gebhart/patrepeval huggingface dataset:
Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. (1992)

The status of fasting triglycerides as a risk factor for coronary artery disease (CAD) has been considered weak because in multivariate analyses, triglycerides tend to be eliminated by high density lipoprotein (HDL) cholesterol. To further evaluate the role of triglycerides in CAD, we employed postprandial lipemia as a more informative means of characterizing triglyceride metabolism. In 61 male subjects with severe CAD and 40 control subjects without CAD as verified by angiography, we measured cholesterol; triglycerides; HDL cholesterol; HDL2 cholesterol; and apolipoproteins A-I, A-II, and B in fasting plasma and triglycerides before and 2, 4, 6, and 8 hours after a standardized test meal. Both the maximal triglyceride increase and the magnitude of postprandial lipemia (area under the triglyceride curve over 8 hours after the meal) were higher in cases than in control subjects. Single postprandial triglyceride levels 6 and 8 hours after the meal were highly discriminatory (p < 0.001), and by logistic-regression analysis displayed an accuracy of 68% in predicting the presence or absence of CAD. In this respect, accuracy was higher than that of HDL2 cholesterol (64%) and equal to that of apolipoprotein B (68%), the most discriminatory fasting parameter. Multivariate logistic-regression analysis was performed to reduce the number of risk factors to those that were statistically independent. This statistical procedure selected postprandial but not fasting triglycerides into the most accurate multivariate model, which also contained the accepted risk factors HDL2 cholesterol, apolipoprotein B, and age. This model classified 82% of subjects correctly. We conclude that triglycerides are independent predictors of CAD in multivariate analyses including HDL cholesterol, provided that a challenge test of triglyceride metabolism such as postprandial lipemia is used. The study suggests that the metabolism of triglycerides is a critical determinant of cholesterol metabolic routing. The findings support the concept that the negative association between HDL cholesterol levels and CAD actually originates in part from a positive relation between CAD and plasma triglycerides, as ascertained in the postprandial state.
Cystic Fibrosis Pulmonary Guidelines (2007)

Cystic fibrosis (CF) is an autosomal recessive disease characterized by abnormal airways secretions, chronic endobronchial infection, and progressive airway obstruction. The use of medications to slow the progression of lung disease has led to significant improvement in survival. An evidence review of chronic medications for CF lung disease was performed in 2007 to provide guidance to clinicians in evaluating and selecting appropriate treatment for individuals with this disease. We have undertaken a new review of the literature to update the recommendations, including consideration of new medications and additional evidence on previously reviewed therapies. A multidisciplinary committee of experts in CF pulmonary care was established to review the evidence for use of chronic medications for CF lung disease and make treatment recommendations. Published evidence for chronic lung therapies was systematically reviewed and resulting treatment recommendations were graded based on the United States Preventive Services Task Force scheme. These guidelines provide up-to-date evidence of safety and efficacy of chronic treatments of CF lung disease, including the use of novel therapies that have not previously been included in CF pulmonary guidelines.
Proteins with selected sequences fold into unique native conformation (1994)

We design sequences of 80-monomer model protein which provide very low energy in the target (``native'') structure. Then the designed sequence is subjected to lattice Monte Carlo simulation of folding. In all runs model protein folded from random coil to the unique native conformation, effectively ``solving'' the multiple minima problem. These results suggest that thermodynamically oriented selection of sequences which makes the native conformation a pronounced deep minimum of energy solves the problem of kinetic accessibility of this conformation as well.
Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands (2008)

Sigma (sigma) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of sigma receptors, termed sigma(1) and sigma(2). Of these two subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for sigma(1) receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors. Certain neurosteroids are known to interact with sigma(1) receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca(2+) signaling. Sigma(1) receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, sigma(1) receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the role of sigma(1) receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of sigma(1) ligands.
Antibody against Surface-Bound C5a Peptidase Is Opsonic and Initiates Macrophage Killing of Group B Streptococci (2001)

The capsular polysaccharides of group B streptococci (GBS) are a primary focus of vaccine development. Immunogenicity and long-lasting protection are best achieved by conjugating polysaccharides to a T-cell-dependent protein antigen. Streptococcal C5a peptidase (SCPB) is a conserved surface protein that is expressed by all streptococcal serotypes tested to date, and it is a possible carrier protein that could itself induce a protective immune response. Clearance of GBS from lungs, mucosal surfaces, or blood probably depends on the opsonophagocytic response of tissue-specific macrophages and polymorphonuclear leukocytes (PMNs). In this study, we examined the potential of antibody directed against SCPB from a serotype II strain to enhance the capacity of mouse bone marrow macrophages (from primary cultures) and human PMNs in whole blood to kill GBS in vitro. Our experiments demonstrated that Streptococcus serotypes Ia, Ib, II, III, and V, preopsonized with anti-SCPB antibody, were killed more rapidly by cultured macrophages and PMNs in whole blood than were nonopsonized GBS. The increased rate of killing was accompanied by an increased macrophage oxidative burst. Furthermore, opsonization was serotype transparent. Immunization with SCPB conjugated to capsular polysaccharide type III produced polysaccharide-specific antibodies. It is interesting that this antiserum promoted serotype-independent killing of streptococci. These data support the use of SCPB in a GBS polysaccharide conjugate vaccine. SCPB not only enhanced the immunogenicity of polysaccharide components of the vaccine, but it might also induce additional serotype-independent protective antibodies.
Production of Citric Acid by Mutants of Aspergillus niger (1956)

Summary: Mutants of Aspergillus niger, Wisconsin strain 72–4, were produced by multiple X-ray and ultraviolet irradiation. The mutants differed from the parent strain culturally and in citric acid production. Comparison between the yields of citric acid from the parent strain and mutants showed significant increases with the latter. In crude sugar media, such as ferrocyanide-treated brown sugar, yields of citric acid equivalent to 80% of the sugar fermented were obtained in aerated culture, whereas only 21% was obtained with the parent strain.
Serum Microarrays for Large Scale Screening of Protein Levels (2005)

There is a great need for comprehensive proteomic analysis of large patient cohorts of plasma and serum samples to identify biomarkers of human diseases. Here we describe a new antibody-based proteomic approach involving a reverse array format where serum samples are spotted on a microarray. This enables all samples to be screened for their content of a certain serum protein in a single experiment using target-recognizing antibodies and fluorescently labeled secondary antibodies. The procedure is illustrated with the analysis of the IgA levels in 2009 spotted serum samples, and the data are compared with clinical routine measurements. The results suggest that it is possible to simultaneously screen thousands of complex clinical serum samples for their content of the relative amount of specific serum proteins of clinical relevance.
Immunotherapy for B-Cell Neoplasms Using T-Cells Expressing Chimeric Antigen Receptors : From Antigen Choice to Clinical Implementation (2012)

Immunotherapy with T cells expressing chimeric antigen receptors (CAR) is being evaluated as a potential treatment for B-cell neoplasms. In recent clinical trials it has shown promising results. As the number of potential candidate antigens expands, the choice of suitable target antigens becomes more challenging to design studies and to assess optimal efficacy of CAR. Careful evaluation of candidate target antigens is required to ensure that T cells expressing CAR will preferentially kill malignant cells with a minimal toxicity against normal tissues. B cells express specific surface antigens that can theoretically act as targets for CAR design. Although many of these antigens can stimulate effective cellular immune responses in vivo, their implementation in clinical settings remains a challenge. Only targeted B-cell antigens CD19 and CD20 have been tested in clinical trials. This article reviews exploitable B cell surface antigens for CAR design and examines obstacles that could interfere with the identification of potentially useful cellular targets.
Homeostatic maintenance of natural Foxp3 + CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization (2005)

Interleukin (IL)-2 plays a crucial role in the maintenance of natural immunologic self-tolerance. Neutralization of circulating IL-2 by anti-IL-2 monoclonal antibody for a limited period elicits autoimmune gastritis in BALB/c mice. Similar treatment of diabetes-prone nonobese diabetic mice triggers early onset of diabetes and produces a wide spectrum of T cell-mediated autoimmune diseases, including gastritis, thyroiditis, sialadenitis, and notably, severe neuropathy. Such treatment selectively reduces the number of Foxp3-expressing CD25(+) CD4(+) T cells, but not CD25(-) CD4(+) T cells, in the thymus and periphery of normal and thymectomized mice. IL-2 neutralization inhibits physiological proliferation of peripheral CD25(+) CD4(+) T cells that are presumably responding to normal self-antigens, whereas it is unable to inhibit their lymphopenia-induced homeostatic expansion in a T cell-deficient environment. In normal naive mice, CD25(low) CD4(+) nonregulatory T cells actively transcribe the IL-2 gene and secrete IL-2 protein in the physiological state. IL-2 is thus indispensable for the peripheral maintenance of natural CD25(+) CD4(+) regulatory T cells (T reg cells). The principal physiological source of IL-2 for the maintenance of T reg cells appears to be other T cells, especially CD25(low) CD4(+) activated T cells, which include self-reactive T cells. Furthermore, impairment of this negative feedback loop via IL-2 can be a cause and a predisposing factor for autoimmune disease.
Estrogen receptor-directed radiotoxicity with Auger electrons: specificity and mean lethal dose. (1992)

To assess the feasibility of using estrogen receptor-directed therapy with Auger electron-emitting ligands for therapy of estrogen receptor (ER)-containing cancers, we synthesized and evaluated the radiotoxicity of several 123I-labeled estrogens to specifically kill ER+ cells in culture. Auger electrons have been previously shown to be of short range, generally less than the dimensions of a cell, so that to use them therapeutically a mechanism is needed to deliver the Auger electron-emitting nuclide to the vicinity of the DNA. Since it is now well established that the estrogen receptor, when bound to estrogen, forms a high affinity association with distinct estrogen response elements in the DNA, we wished to test the hypothesis that a short exposure of cells to a 123I-labeled estrogen would be specifically radiotoxic to ER+ cells, and that the decays per cell needed for cell killing would be compatible with reasonable levels of receptor occupancy. Using the halodestannylation reaction with tributyl tin precursors of several estrogens and commercially available iodine-123, we prepared the iodoestrogens, E-17 alpha(-)[123I]-iodo-11 beta-methoxyestradiol and 2(-)[123I]iodo-1,1-bis(4-hydroxyphenyl)--2-phenylethylene, at high specific activities, in several cases at essentially the specific activity of 123I itself, 240,000 Ci/mmol. When various concentrations of either of the 123I-labeled estrogens were incubated for 1 h with a subline of ER+ Chinese hamster ovary cells and the washed cells plated for survival assays, a dose-dependent, unlabeled estradiol-inhibitable reduction in survival was observed. In contrast, Chinese hamster ovary cells not expressing estrogen receptor showed little sensitivity to the radiotoxicity of the 123I-labeled estrogens. Calculations based on the assayed residence time of the iodoestrogens in the cells indicate that several hundred decays per cell are sufficient to kill cells.
[Contamination of bovine fetal serum with bovine viral diarrhea virus]. (2000)

Fetal bovine serum (FBS) used in cell culture may be contaminated with viruses, among them bovine viral diarrhea virus (BVDV) affecting the production of biological reagents and the results of diagnosis. The filtration process used in the preparation of commercial FBS abrogates most viral agents that may be present in raw FBS, but BVDV may pass through the filters because of its small size and its pleomorphism. While detection of bovine herpes virus-1 and parainfluenza-3 (PI-3) is determined by observation of the cytopathic effect, and also by hemadsorption in the case of PI-3, the most frequently isolated BVDV is non cytopathic, and infects cells without morphological alterations, inducing problems that arise after several cell generations. Batches of raw and processed FBS were analyzed. Frequencies of BVDV detection in raw serum in Argentina were similar to those published for USA. By conventional methods for BVDV detection, only 2 of 20 commercial batches of FBS had BVDV. Using cell cultures maintained with high concentrations of the serum under study for at least 2 weeks, with detection of viral antigen by indirect immunofluorescence, the percentage of BVDV detection was 80%. This method shows that most lots of commercial FBS contain BVDV. RT-PCR allows faster detection of the viral genome, but it must be validated, as it does not show viral replication. To eliminate the problem of BVDV contamination in FBS, only gamma irradiated FBS is used in our laboratory.
ChemInform Abstract: Hydrolysis Products of Flavins (Isoalloxazines). (1987)

Abstract Hydrolysis of the flavins (I) with Triton B yields the spirohydantoins (II) and the imidazoquinoxalines (III) as main products.
Fine-grained dynamic voltage scaling on OLED display (2012)

Organic Light Emitting Diode (OLED) has emerged as the new generation display technique for mobile multimedia devices. Compared to existing technologies OLEDs are thinner, brighter, lighter, and cheaper. However, OLED panels are still the biggest contributor to the total power consumption of mobile devices. In this work, we proposed a fine-grained dynamic voltage scaling (FDVS) technique to reduce the OLED power. An OLED panel is partitioned into multiple display areas of which the supply voltage is adaptively adjusted based on the displayed content. A DVS-friendly OLED driver design is also proposed to enhance the color accuracy of the OLED pixels at the scaled supply voltage. Our experimental results show that compared to the existing global DVS technique, FDVS technique can achieve 25.9%&#x223C;43.1% more OLED power saving while maintaining a high image quality measured by Structural Similarity Index (SSIM=0.98). The further analysis shows shat FDVS technology can also effectively reduce the color remapping cost when color compensation is required to improve the image quality of an OLED panel working at a scaled voltage.
A transcription factor regulatory circuit in differentiated pancreatic cells (2001)

Mutations in the human genes encoding hepatocyte nuclear factors (HNF) 1alpha, 1beta, 4alpha, and IPF1(PDX1/IDX1/STF1) result in pancreatic beta cell dysfunction and diabetes mellitus. In hepatocytes, hnf4alpha controls the transcription of hnf1alpha, suggesting that this same interaction may operate in beta cells and thus account for the common diabetic phenotype. We show that, in pancreatic islet and exocrine cells, hnf4alpha expression unexpectedly depends on hnf1alpha. This effect is tissue-specific and mediated through direct occupation by hnf1alpha of an alternate promoter located 45.6 kb from the previously characterized hnf4alpha promoter. Hnf1alpha also exerts direct control of pancreatic-specific expression of hnf4gamma and hnf3gamma. Hnf1alpha dependence of hnf4alpha, hnf4gamma, hnf3gamma, and two previously characterized distal targets (glut2 and pklr) is established only after differentiated cells arise during pancreatic embryonic development. These studies define an unexpected hierarchical regulatory relationship between two genes involved in human monogenic diabetes in the cells, which are relevant to its pathophysiology. Furthermore, they indicate that hnf1alpha is an essential component of a transcription factor circuit whose role may be to maintain differentiated functions of pancreatic cells.
Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. (1981)

We have determined the complete nucleotide sequence of the thymidine kinase (ATP:thymidine 5' phosphotransferase, EC 2.7.1.21) gene of herpes simplex virus type 1 strain CL101 from a plasmid clone of viral DNA derived by Enquist et al. [Enquist, L. W., Vande Woude, G. F., Wagner, M., Smiley, J. R. & Summers, W. C. (1979) Gene 7, 335-342]. A cDNA copy of the 5' end of thymidine kinase mRNA was also analyzed to locate the transcribed sequences. The transcribed portion of the gene is approximately 1300 nucleotides in length and appears to contain no intervening sequences. There is an untranslated region of 107 nucleotides at the 5' end of the mRNA followed by an open reading frame of 1128 nucleotides. The gene is thus capable of coding for a protein of 376 amino acids. Sequences similar to those thought to be involved in control of transcription and translation of a variety of eukaryotic and viral genes such as a "Hogness box" and A-A-T-A-A-A polyadenylylation signals are also present in the herpesvirus thymidine kinase gene.
[Mode of lymph node metastasis in early gastric cancer and risk factors]. (2013)

LNM in EGC is mainly correlated with depth of invasion, and lymphatic vessel involvement. Precise evaluation of LNM pre- and intra-operatively is very important for the reasonable surgery.
Hemostatic studies in racing standardbred horses with exercise-induced pulmonary hemorrhage. Hemostatic parameters at rest and after moderate exercise. (1991)

The purpose of this study was to determine whether a defect in hemostasis might be a factor in the etiology of exercise-induced pulmonary hemorrhage (EIPH). Hemostatic parameters were evaluated in 22 EIPH-positive and ten EIPH-negative racing horses while in a rested state. Nineteen EIPH-positive and ten EIPH-negative horses were further evaluated just before and immediately after a 15 min exercise period on a 260 m oval track. When EIPH-positive and EIPH-negative horses were compared at rest, there was no significant difference in any of the coagulation and fibrinolytic parameters studied. There was however, a significant difference in platelet function as assessed by aggregometry. The platelets from affected horses were significantly less responsive than those from nonaffected horses when exposed in vitro to the platelet agonists adenosine diphosphate, collagen and platelet activating factor. Exercise tended to increase the packed cell volume and factor VIII/von Willebrand factor and to decrease platelet aggregation responses to low concentrations of adenosine diphosphate. These effects of exercise however were quantitatively similar in both EIPH-positive and EIPH-negative horses. Reduced platelet function may therefore be a contributing factor in the bleeding characteristic of horses with EIPH.
Preparation of Monodispersed Fe−Mo Nanoparticles as the Catalyst for CVD Synthesis of Carbon Nanotubes (2001)

Uniform iron−molybdenum nanoparticles were prepared by thermal decomposition of metal carbonyl complexes using a mixture of long-chain carboxylic acid and long-chain amine as protective agents. The sizes of the nanoparticles can be systematically varied from 3 to 14 nm by changing the experimental conditions. High-resolution TEM images and EDX data show that the prepared nanoparticles are highly crystalline iron nanoparticles containing ≈4% molybdenum. The effects of the concentration, reaction time, the ratio of metal carbonyl complexes versus protective agents, and the ratio of acid/amine of the protective agents on the sizes of the produced nanoparticles were systematically studied. The prepared nanoparticles were used as catalysts for single-walled carbon nanotube growth and the results indicate that there is an upper limit for the size of the catalyst particles to nucleate single-walled carbon nanotubes.
Effectiveness of LANAP over time as measured by tooth loss. (2013)

This study examines the effectiveness of the laser-assisted new attachment procedure (LANAP) as measured by tooth loss, comparing data to published studies using conventional surgical treatment modalities for the primary treatment of Types III and IV periodontitis. Retrospective data from 107 patients presenting with Types III and IV periodontitis were gathered and evaluated. All patients received LANAP periodontal therapy as their primary surgical treatment according to the FDA-cleared LANAP protocol. The patients averaged 6.2 years post-treatment. The data were compared to several published studies for outcome classification and tooth loss over time. The effectiveness of LANAP as a primary treatment method for Types III and IV periodontitis compares very favorably with conventional surgical treatment modalities concerning tooth loss and stability over time, need for surgical retreatment, and outcome classification. Dentistry continues to develop less invasive means of providing patient care without sacrificing results. Less invasive treatment of periodontitis, with reduced postoperative morbidity yet equal results in tooth retention over time is an important goal. LANAP treatment for moderate and advanced periodontitis provides a less invasive treatment alternative for the dentist and patient to consider as a part of informed consent.