gebhart/patrepeval huggingface dataset:
Electromagnetic fields applied to the reduction of abdominal obesity (2011)

Facing an alarming increase in overweight and obesity and considering the current therapeutic gear offering various results, it seems interesting to propose an efficient technique for the reduction of abdominal obesity. The clinical study demonstrated the safety and efficiency of the device for the reduction of abdominal obesity. Treatment showed itself efficient with patients who were not committed to any weight loss program.
The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma (2006)

A critical role for vascular endothelial factor (VEGF) has been demonstrated in multiple myeloma (MM) pathogenesis. Here, we characterized the effect of the small-molecule VEGF receptor inhibitor pazopanib on MM cells in the bone marrow milieu. Pazopanib inhibits VEGF-triggered signaling pathways in both tumor and endothelial cells, thereby blocking in vitro MM cell growth, survival, and migration, and inhibits VEGF-induced up-regulation of adhesion molecules on both endothelial and tumor cells, thereby abrogating endothelial cell-MM cell binding and associated cell proliferation. We show that pazopanib is the first-in-class VEGF receptor inhibitor to inhibit in vivo tumor cell growth associated with increased MM cell apoptosis, decreased angiogenesis, and prolonged survival in a mouse xenograft model of human MM. Low-dose pazopanib demonstrates synergistic cytotoxicity with conventional (melphalan) and novel (bortezomib and immunomodulatory drugs) therapies. Finally, gene expression and signaling network analysis show transcriptional changes of several cancer-related genes, in particular c-Myc. Using siRNA, we confirm the role of c-Myc in VEGF production and secretion, as well as angiogenesis. These preclinical studies provide the rationale for clinical evaluation of pazopanib, alone and in combination with conventional and novel therapies, to increase efficacy, overcome drug resistance, reduce toxicity, and improve patient outcome in MM.
PET imaging of prostate cancer with 11C-acetate. (2003)

Prostate cancer is second only to lung cancer as the leading cause of cancer deaths in American men. In 1997, approximately 209,900 new cases of prostate cancer were diagnosed, and more than 41,800 deaths were attributed to this malignancy ([1][1]). Primary or recurrent prostate cancer can be
Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1. (1991)

Ovine trophoblast protein-1 (oTP-1) is the alpha-interferon (IFN alpha) variant, secreted by conceptuses and referred to as type I trophoblast interferon, that is responsible for maternal recognition of pregnancy in sheep. We have previously shown that oTP-1 is as potent an antiviral agent as any known IFN. IFNs also possess anticellular activity and are, in fact, used in cancer therapy and have been found to be effective in the treatment of cancer such as myelogenous and hairy cell leukemias. A significant problem with the currently used IFNs is the undesirable side effect of toxicity at high concentrations. In this study, we examined the anticellular activity and toxicity of oTP-1. It inhibited proliferation but did not exhibit toxicity at high concentrations, unlike known IFN alpha S. In an anticellular assay using colony formation of both the human amnionic line, WISH, and the bovine epithelial line, MDBK, oTP-1 inhibited both colony size and number. oTP-1 was as effective as human and bovine IFN alpha s on human and bovine cells, respectively; thus, it displays potent cross-species activity. Its activity was dose dependent, and inhibition of proliferation could be observed at concentrations as low as 1 unit/ml. Concentrations as high as 50,000 units/ml stopped proliferation, while viability was not impaired. Cell cycle analysis revealed an increased proportion of cells in S phase and a corresponding decreased proportion of cells in G2/M after 48 h of oTP-1 treatment. Therefore, oTP-1 appears to inhibit progress of cells through S phase. oTP-1 antiproliferative effects can be observed as early as 12 h after after the initiation of culture and are maintained through 6 days. Thus, oTP-1 exhibits potent anticellular activity without toxicity across species and may have therapeutic potential as an antitumor agent without the toxic effects generally associated with IFNs.
Cytosolic p53 protein and serum p53 autoantibody evaluation in breast cancer. Comparison with prognostic factors. (2000)

Mutations of the TP53 gene induce the production of an abnormal protein (p53) with a prolonged half-life allowing its detection by monoclonal antibodies and leading to a development of serum p53 autoantibodies. We have quantified the protein p53 in 196 cytosols of primary breast cancer tissues, by an immunoluminometric method and searched for p53 autoantibodies in the sera of 101 patients, by an immunoenzymatic assay. The median value has been chosen as cut-off (0.26 ng/mg protein). 18.4% of tumors had a p53 level < 0.10 ng/mg protein, and 8.2% had a p53 level > or = 2.5 ng/mg protein (range: 0.43.37). We found a significant difference between p53 distribution (p = 0.003) and median level (p = 0.001) in ductal and lobular carcinomas. The p53 median levels were significantly different between the grade III versus the grade I tumors (p = 0.01) and versus the grade II tumors (p = 0.008). An inverse correlation was obtained between p53 levels and ER (p = 0.003) alone or with PR (p = 0.006). p53 autoantibodies were detected in 7.9% of cases (8/101). This p53 study shows correlations with some poor prognostic factors, but would require further evaluation to better define the patient groups with poor prognosis. The p53 detection autoantibodies is neither correlated with the p53 cytosolic assay nor with prognostic factors of breast cancer, and should therefore not be used for patient the selection of the patient groups with poor prognosis.
High-Throughput Fluorescence-Based Screening Assays for Tryptophan-Catabolizing Enzymes (2014)

Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are two structurally different enzymes that have a different tissue distribution and physiological roles, but both catalyze the conversion of tryptophan to N-formylkynurenine (NFK). IDO1 has been clinically validated as a small-molecule drug target for cancer, while preclinical studies indicate that TDO may be a target for cancer immunotherapy and neurodegenerative disease. We have developed a high-throughput screening assay for IDO1 and TDO based on a novel chemical probe, NFK Green, that reacts specifically with NFK to form a green fluorescent molecule with an excitation wavelength of 400 nm and an emission wavelength of 510 nm. We provide the first side-by-side comparison of a number of published inhibitors of IDO1 and TDO and reveal that the preclinical IDO1 inhibitor Compound 5l shows significant cross-reactivity with TDO, while the relative selectivity of other published inhibitors was confirmed. The suitability for high-throughput screening of the assays was demonstrated by screening a library of 87,000 chemical substances in 384- or 1536-well format. Finally, we demonstrate that the assay can also be used to measure the capacity of cells to metabolize tryptophan and to measure the cellular potency of IDO1 and TDO inhibitors.
Terminal Deoxynucleotidyl Transferase Indiscriminately Incorporates Ribonucleotides and Deoxyribonucleotides (2001)

Terminal deoxynucleotidyl transferase (TdT) catalyzes the condensation of deoxyribonucleotides on 3'-hydroxyl ends of DNA strands in a template-independent manner and adds N-regions to gene segment junctions during V(D)J recombination. Although TdT is able to incorporate a few ribonucleotides in vitro, TdT discrimination between ribo- and deoxyribonucleotides has never been studied. We found that TdT shows only a minor preference for incorporation of deoxyribonucleotides over ribonucleotides on DNA strands. However, incorporation of ribonucleotides alone or in the presence of deoxyribonucleotides generally leads to premature chain termination, reflecting an impeded accommodation of ribo- or mixed ribo/deoxyribonucleic acid substrates by TdT. An essential catalytic aspartate in TdT was identified, which is a first step toward understanding the apparent lack of sugar discrimination by TdT.
Structural Convergence in the Active Sites of a Family of Catalytic Antibodies (1997)

The x-ray structures of three esterase-like catalytic antibodies identified by screening for catalytic activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. The high resolution structures account for catalysis by transition state stabilization, and in all three antibodies a tyrosine residue participates in the oxyanion hole. Despite significant conformational differences in their combining sites, the three antibodies, which are the most efficient among those elicited, achieve catalysis in essentially the same mode, suggesting that evolution for binding to a single TSA followed by screening for catalysis lead to antibodies with structural convergence.
G-Protein-coupled Receptors: Regulatory Role of Receptor Kinases and Arrestin Proteins (1992)

Receptors that couple to guanine nucleotide regulatory proteins comprise an extraordinarily diverse collection of functional entities. They mediate responses to stimuli as varied as neurotransmitters, hormones, chemoattractants, cytokines, odorants, and even photons of light (Dohlman et al. 1991). It has become increasingly clear that the functional and regulatory properties of these receptors are remarkably conserved, mirroring the substantial conservation of their structure and topographical features. Activation of such receptors with agonists or other stimuli leads to conformational changes that render the receptors "active." At least two major pathways exist along which the activated receptors may proceed. One pathway involves interaction with G protein, activation of a biochemical effector, and generation of a physiological response. The other pathway involves interaction with proteins other than the G proteins, leading to other fates not involving activation of physiological responses. Perhaps the best-studied of such pathways is that by which the activated receptors interact...
Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils (2003)

Human polymorphonuclear leukocytes (PMNs or neutrophils) are essential to the innate immune response against bacterial pathogens. Recent evidence suggests that PMN apoptosis facilitates resolution of inflammation during bacterial infection. Although progress has been made toward understanding apoptosis in neutrophils, very little is known about transcriptional regulation of this process during bacterial infection. To gain insight into the molecular processes that facilitate resolution of infection, we measured global changes in PMN gene expression during phagocytosis of a diverse group of bacterial pathogens. Genes encoding key effectors of apoptosis were up-regulated, and receptors critical to innate immune function were down-regulated during apoptosis induced by phagocytosis of Burkholderia cepacia, Borrelia hermsii, Listeria monocytogenes, Staphylococcus aureus, and Streptococcus pyogenes. Importantly, we identified genes that comprise a common apoptosis differentiation program in human PMNs after phagocytosis of pathogenic bacteria. Unexpectedly, phagocytosis of Str. pyogenes induced changes in neutrophil gene expression not observed with other pathogens tested, including down-regulation of 21 genes involved in responses to IFN. Compared with other bacteria, PMN apoptosis was significantly accelerated by Str. pyogenes and was followed by necrosis. Thus, we hypothesize that there are two fundamental outcomes for the interaction of bacterial pathogens with neutrophils: (i) phagocytosis of bacteria induces an apoptosis differentiation program in human PMNs that contributes to resolution of bacterial infection, or (ii) phagocytosis of microorganisms such as Str. pyogenes alters the apoptosis differentiation program in neutrophils, resulting in pathogen survival and disease.
An alternative polynomial representation of the wavefront error function (2002)

Purpose

Despite the good mathematical properties of Zernike polynomials, their fit to the wavefront error functions or height data from a videokeratoscope may not always be adequate. This occurs mainly because Zernike polynomials are global functions and are not suitable for characterizing local changes. A question arises whether a set of functions exists that would result in better modeling of the wavefront error function. 

Methods

We used our recently reported Bhatia-Wolf polynomial based method (IEEE Trans. on Biomed. Eng. Vol. 49, 2002, in press) as an alternative for modeling the wavefront error functions and compared it to the traditional Zernike polynomial based modeling. 

Results

The modeling error (RMS) of the Bhatia-Wolf polynomial based method is always smaller than that of the Zernike polynomials for a given radial order. For normal subjects it was observed that reduction in the modeling error was in the range of 30% to 50%. For subjects with significant aberrations (e.g. severe keratoconus), the decrease in the MSE was tenfold. Although some of the lower order terms of the Bhatia-Wolf polynomial expansion may not be directly recognized as a commonly known type of aberration, their use in fitting gives a significant improvement in wavefront estimation. We provide a physical explanation for these terms and introduce the concept of generalized defocus. 

Conclusion

The use of Bhatia-Wolf polynomial based modeling of the wavefront error function is a viable alternative to the Zernike polynomial representation. This is particularly important in areas such as customized refractive surgery, where the information from the Zernike polynomial fit may be directly used.
Antagonists and non-toxic variants of the dominant wheat gliadin T cell epitope in coeliac disease (2005)

Altered peptide ligands of p57-73 QE65, identified using polyclonal T cells from multiple HLA-DQ2+ CD donors, have properties in vitro that suggest that a single substitution to certain alpha/beta-gliadins could abolish their capacity to stimulate IFN-gamma from CD4 T cells and also have anti-inflammatory or protective effects in HLA-DQ2+ CD.
Post-Failure Routing Performance with Multiple Routing Configurations (2007)

The slow convergence of IGP routing protocols after a topology change has led to several proposals for proactive recovery schemes in IP networks. These proposals are limited to guaranteeing loop-free connectivity after a link or node failure, and do not take into account the resulting load distribution in the network. This can lead to congestion and packet drops. In this work, we show how a good load distribution can be achieved in pure IP networks immediately after a link failure, when multiple routing configurations (MRC) is used as a fast recovery mechanism. This paper is the first attempt to improve the load balancing when a proactive recovery scheme is used. Unlike load balancing methods used with normal IP rerouting, our method does not compromise on the routing performance in the failure free case. Our method is evaluated using simulations on several real and synthetically generated network topologies. The evaluation shows that our method yields good routing performance, making it feasible to use MRC to handle transient network failures.
Pedicle Morphology of the Immature Thoracolumbar Spine (2000)

The data in this study indicates that pedicle screws may be used in the adolescent spine. However, care should taken to accurately ascertain pedicle size before surgery so that improper use of screws can be avoided. Growth of the pedicles in relation to the spinal canal indicates that the increase in pedicle size is lateral to the spinal canal.
Antisense Oligonucleotide Inhibition of Hepatitis C Virus (HCV) Gene Expression in Livers of Mice Infected with an HCV-Vaccinia Virus Recombinant (1999)

Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there is an urgent need for both novel therapeutic agents and small-animal models which can be used to evaluate candidate drugs. A small-animal model of HCV gene expression was developed with recombinant vaccinia virus vectors. VHCV-IRES (internal ribosome entry site) is a recombinant vaccinia viral vector containing the HCV 5' nontranslated region (5'-NTR) and a portion of the HCV core coding region fused to the firefly luciferase gene. Intraperitoneal injection of VHCV-IRES produced high levels of luciferase activity in the livers of BALB/c mice. Antisense oligonucleotides complementary to the HCV 5'-NTR and translation initiation codon regions were then evaluated for their effects on the expression of these target HCV sequences in BALB/c mice infected with the vaccinia virus vector. Treatment of VHCV-IRES-infected mice with 20-base phosphorothioate oligonucleotides complementary to the sequence surrounding the HCV initiation codon (nucleotides 330 to 349) specifically reduced luciferase expression in the livers in a dose-dependent manner. Inhibition of HCV reporter gene expression in this small-animal model suggests that antisense oligonucleotides may provide a novel therapy for treatment of chronic HCV infection.
Impaired Leucocyte Functions in Diabetic Patients (1997)

This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.
Different secretory immunoglobulin A antibody responses to cholera vaccination in Swedish and Pakistani women (1980)

The capacity of subcutaneous cholera vaccination to induce an antibody response in milk and saliva was studied in lactating Swedish and Pakistani women, since secretory immunoglobulin A (SIgA) antibody responses in these secretions may reflect intestinal immunity. Before immunization, most of the Pakistani women had significant titers of specific SIgA antibodies against Vibrio cholerae lipopolysaccharide in milk, whereas only a few of the Swedish women had measurable, low titers. In the Pakistani women a single subcutaneous injection of cholera vaccine gave rise to a significant SIgA titer rise in 70% of the milk and 45% of the saliva samples. The Swedish women, on the other hand, did not respond with a significant antibody response of any immunoglobulin class in milk or saliva, either after a single or after a booster dose 14 days later. In serum, however, the vaccination induced significant titer rises, mainly of IgG antibodies, also in the Swedish women, but these rises were of lower magnitude than those in the Pakistani group. The results suggest a significant difference in the capacity of parenterally administered cholera vaccine to stimulate SIgA antibody formation in naturally primed and nonprimed individuals.
Population-Based Study of Herpes Zoster and Its Sequelae (1982)

The epidemiology of herpes zoster and its sequelae have been investigated in a community-based study. The incidence rates observed in Rochester, Minnesota, are lower than those determined in practice-based series; and this may reflect some selectivity in practice-based series compared to population-based studies. No significant sex difference or seasonal variation was observed but the incidence did increase markedly with age. An increase in incidence was also observed over the 15-year period studied. The dermatomal distribution of herpes zoster observed in Rochester was quite similar to previous studies, despite their inherent biases in case ascertainment, except for a lower proportion with cranial nerve zoster. Herpes ophthalmicus (V1) appears to affect a slightly different population than zoster of the other dermatomes, with elderly males being more at risk. Also, herpes ophthalmicus is associated with a higher complication rate compared to the other dermatomes primarily due to the fragility of the involved organ. The elderly are also at greatest risk for the most common complication, post-herpetic neuralgia. The rate of PHN is not significantly increased in any particular dermatome but is significantly decreased in lumbar herpes zoster.
Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances (2008)

The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model-based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q-, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.