gebhart/patrepeval huggingface dataset:
Chronic bronchiectasis and anti-myeloperoxidase antibody related rapidly progressive necrotizing glomerulonephritis. (1998)

We reported two cases of chronic bronchiectasis and rapidly progressive necrotizing glomerulonephritis/severe renal failure which were also positive for anti-myeloperoxidase antibody, and followed their treatment and outcome. Immunosuppressive therapy was complicated by superimposed chest infection in both cases. Nonetheless, cautious use of immunosuppressive and antibiotic therapy reversed dialysis-dependent renal failure in one of the two cases.
Natural‐Product Sugar Biosynthesis and Enzymatic Glycodiversification (2008)

Many biologically active small-molecule natural products produced by microorganisms derive their activities from sugar substituents. Changing the structures of these sugars can have a profound impact on the biological properties of the parent compounds. This realization has inspired attempts to derivatize the sugar moieties of these natural products through exploitation of the sugar biosynthetic machinery. This approach requires an understanding of the biosynthetic pathway of each target sugar and detailed mechanistic knowledge of the key enzymes. Scientists have begun to unravel the biosynthetic logic behind the assembly of many glycosylated natural products and have found that a core set of enzyme activities is mixed and matched to synthesize the diverse sugar structures observed in nature. Remarkably, many of these sugar biosynthetic enzymes and glycosyltransferases also exhibit relaxed substrate specificity. The promiscuity of these enzymes has prompted efforts to modify the sugar structures and alter the glycosylation patterns of natural products through metabolic pathway engineering and enzymatic glycodiversification. In applied biomedical research, these studies will enable the development of new glycosylation tools and generate novel glycoforms of secondary metabolites with useful biological activity.
Phase I Pilot Trial of the Bispecific Antibody MDXH210 (anti-FcγRI X anti–HER-2/neu) in Patients Whose Prostate Cancer Overexpresses HER-2/neu (2001)

The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER-2/neu proto-oncogene product. Patients with prostate cancer that expressed HER-2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor-alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER-2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate-specific antigen levels.
A local update strategy for iterative reconstruction from projections (1993)

A method for Bayesian reconstruction which relies on updates of single pixel values, rather than the entire image, at each iteration is presented. The technique is similar to Gauss-Seidel (GS) iteration for the solution of differential equations on finite grids. The computational cost per iteration of the GS approach is found to be approximately equal to that of gradient methods. For continuously valued images, GS is found to have significantly better convergence at modes representing high spatial frequencies. In addition, GS is well suited to segmentation when the image is constrained to be discretely valued. It is shown that Bayesian segmentation using GS iteration produces useful estimates at much lower signal-to-noise ratios than required for continuously valued reconstruction. The convergence properties of gradient ascent and GS for reconstruction from integral projections are analyzed, and simulations of both maximum-likelihood and maximum a posteriori cases are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of Oxygen on PbS Films (1955)

The effect of oxygen on the conductivity of vacuum evaporated PbS films has been experimentally investigated. When outgassed these films are n-type semiconductors. If they are exposed to oxygen at temperatures below about 200°C, the conductivity decreases with increasing pressure and then increases again. The thermoelectric power changes from negative to positive, but less than 10—3 moleO2/molePbS is sorbed by the film. Above 200°C the conductivity merely decreases when oxygen is admitted, and the thermoelectric power becomes small. The film gradually absorbs all the oxygen in the vacuum system and evolves a good deal of SO2. When the reaction is complete, the conductivity returns to its initial value, and the thermoelectric power is once again negative. The film can repeatedly absorb large amounts of oxygen without there being any permanent change in electrical properties. It is concluded that these films are composed of two layers. Next to the substrate there is a conducting layer that chemisorbs oxygen but does not react with it. The chemisorbed oxygen acceptors are responsible for the observed changes in conductivity. The upper layer of the film is nonconducting and reacts to completion with oxygen, possibly forming PbSO3:PbO, and evolving SO2.
In situ demonstration of mature oligodendrocytes and their processes: An immunocytochemical study with a new monoclonal antibody, Rip (1989)

This paper introduces "Rip" a monoclonal antibody that produces relatively complete staining of oligodendrocytes and their processes in the adult central nervous system (CNS). The distribution of Rip immunoreactivity coincides with that of myelinated axons in both the spinal cord and the cerebellum. In addition, double-immunolabeling experiments demonstrate that Rip stains processes containing myelin basic protein but does not stain processes that express glial fibrillary acidic protein. These results indicate that Rip selectively stains oligodendrocytes but not astrocytes. Moreover, individual Rip-stained oligodendrologial somata and their cytoplasmic processes were observable at both the light microscopic and electron microscopic level when the staining of myelin was reduced. This was accomplished by omitting detergents from antibody incubation steps. Rip-stained oligodendrocytes have multiple processes of varying thickness, some of which end in close proximity to myelin sheaths. These immunostained profiles, reminiscent of those observed in oligodendrocytes stained by Golgi methods, are unique to Rip and indicate that its immunoreactivity is distinct from that of existing serological markers for oligodendrocytes.
Molecular cloning and expression of a glycosaminoglycan N-acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-producing cell line. (1994)

Heparin has a higher content of N-sulfated glucosamine and L-iduronic acid than heparan sulfate. Deacetylation of N-acetylglucosamine followed by N-sulfation may be important steps differentiating the biosynthesis of these glycosaminoglycans. We have cloned, by cross-hybridization with the cDNA from rat liver heparan sulfate N-deacetylase/N-sulfotransferase, a protein from a heparin synthesizing mastocytoma derived cell line called MST. This protein, which has both N-deacetylase/N-sulfotransferase activities, has a predicted amino acid sequence homology of 70% with the above rat liver enzyme and is unique for the following reasons. 1) It was found to be encoded by a 3.8-kilobase mRNA that was unique to heparin-producing cells; an 8.5-kilobase mRNA encoding the rat liver enzymes has been found to occur in all mammalian cells tested on the basis of nucleic acid cross-hybridization; 2) the protein overexpressed in COS cells in its full-length transmembrane form or as a soluble secreted protein A chimera displayed ratios of N-deacetylase to N-sulfotransferase activities that were 4-8-fold higher than that observed for the enzyme found in liver that is involved in the biosynthesis of heparan sulfate. These results suggest that the MST-derived enzyme is probably unique to the production of heparin in mast cells.
Antibodies to Human Albumin in Cirrhotic Sera (1974)

In a previous paper we described a monoclonal IgM protein with antibody-like activity towards aggregated and native albumin. The present study was initiated to determine whether sera, other than that from patients with macroglobulinemia, contained similar antibody-like activity. It was demonstrated that approximately 40% of the sera from patients with classical Laennec's cirrhosis contained antibodies which agglutinate sheep red blood cells coated with aggregated albumin. The hemagglutinating activity was present in the void volume on Sephadex G-200 chromatography and was shown to be an immunoglobulin by its removal on passage over an anti-L-chain immunoadsorbent column. The immunoglobulin was isolated from cirrhotic sera by chromatography on an albumin immunoadsorbent column. The acid eluate from the albumin affinity column contained only IgA. After labeling this IgA with (125)I and obtaining the Fabalpha fragment by proteolysis, it was shown that the labeled Fabalpha complexed noncovalently with aggregated albumin. Complex formation between albumin and the cirrhotic IgA and Fabalpha could also be demonstrated utilizing facilitation of hemagglutination of sheep red blood cells coated with aggregated albumin. Appropriate controls consisting of normal and myeloma IgA and myeloma Fabalpha fragments failed to show evidence of complex formation with albumin. We propose that the restriction of the antibody response to the IgA class may result from the formation of antibodies against albumin altered during metabolism in the gastrointestinal tract. A possible role for anti-albumin antibodies in normal albumin catabolism and in the pathogenesis of Laennec's cirhosis is discussed.
Graft purging in autologous bone marrow transplantation: a promise not quite fulfilled. (2004)

Clonogenic tumor cells contained within hematopoietic stem cell (HPC) grafts may contribute to relapse following autologous transplantation. Graft purging involves either in vivo or ex vivo HPC manipulation in order to reduce the level of tumor cell contamination. Some phase II trials suggest that patients who receive purged products may have a superior transplant outcome. Phase I trials demonstrate the feasibility of purging methods including ex vivo graft incubation with chemotherapeutic drugs, monoclonal antibodies and complement, and CD34+ cell selection. A phase II trial in follicular non-Hodgkin's lymphoma demonstrates that patients who receive HPC products purged negative for bcl-2 gene rearrangements have a superior outcome, compared with patients who receive polymerase chain reaction (PCR)-positive products. This finding, however, has not been confirmed in a randomized trial. HPC purging has demonstrated no benefit in a phase III trial in myeloma. Phase II trials in acute myelogenous leukemia show comparable outcomes for patients who receive either purged or unpurged HPC grafts. Limitations of purging include possible progenitor cell loss, delayed engraftment, and qualitative immune defects following transplant. Data to justify routine use of HPC graft purging are insufficient. Phase I and II data support development of phase III trials of both in vivo and in vitro purging methods.
Reduction of cortical TrkA but not p75NTR protein in early‐stage Alzheimer's disease (2004)

Degeneration of cholinergic nucleus basalis (NB) cortical projection neurons is associated with cognitive decline in late-stage Alzheimer's disease (AD). NB neuron survival is dependent on coexpression of the nerve growth factor (NGF) receptors p75(NTR) and TrkA, which bind NGF in cortical projection sites. We have shown previously a significant reduction of NB perikarya expressing p75(NTR) and TrkA protein during the early stages of AD. Whether there is a concomitant reduction in cortical levels of these receptors during the progression of AD is unknown. p75(NTR) and TrkA protein was evaluated by quantitative immunoblotting in five cortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual cortex) of individuals clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Cortical p75(NTR) levels were stable across the diagnostic groups. In contrast, TrkA levels were reduced approximately 50% in mild/moderate and severe AD compared with NCI and MCI in all regions except visual cortex. Mini-Mental Status Examination scores correlated with TrkA levels in anterior cingulate, superior frontal, and superior temporal cortex. The selective reduction of cortical TrkA levels relative to p75(NTR) may have important consequences for cholinergic NB function during the transition from MCI to AD.
Kinetic characteristics of Escherichia coli RNase H1: cleavage of various antisense oligonucleotide-RNA duplexes (1995)

1. The effects of variations in substrates on the kinetic properties of Escherichia coli RNase H were studied using antisense oligonucleotides of various types hybridized to complementary oligoribonucleotides. The enzyme displayed minimal sequence preference, initiated cleavage through an endonucleolytic mechanism near the 3' terminus of the RNA in a DNA-RNA chimera and then was processively exonucleolytic. Phosphorothioate oligodeoxynucleotides hybridized to RNA supported cleavage more effectively than phosphodiester oligodeoxynucleotides. Oligonucleotides comprised of 2'-methoxy-, 2'-fluoro- or 2'-propoxy-nucleosides did not support RNase H1 activity. 2. The Km and Vmax. of cleavage of RNA duplexes with full phosphorothioate oligodeoxynucleotides were compared with methoxy-deoxy 'gapmers', i.e.; oligonucleotides with 2'-methoxy wings surrounding a deoxynucleotide centre. Such structural modifications resulted in substantial increases in affinity, but significant reductions in cleavage efficiency. The initial rates of cleavage increased as the deoxynucleotide gap size was increased. Multiple deoxynucleotide gaps increased the Vmax. but had little effect on Km. 3. The effects of several base modifications on the site of initial cleavage, processivity and initial rate of cleavage were also studied.
A synthetic promoter library for constitutive gene expression in Lactobacillus plantarum (2006)

A synthetic promoter library (SPL) for Lactobacillus plantarum has been developed, which generalizes the approach for obtaining synthetic promoters. The consensus sequence, derived from rRNA promoters extracted from the L. plantarum WCFS1 genome, was kept constant, and the non-consensus sequences were randomized. Construction of the SPL was performed in a vector (pSIP409) previously developed for high-level, inducible gene expression in L. plantarum and Lactobacillus sakei. A wide range of promoter strengths was obtained with the approach, covering 3-4 logs of expression levels in small increments of activity. The SPL was evaluated for the ability to drive beta-glucuronidase (GusA) and aminopeptidase N (PepN) expression. Protein production from the synthetic promoters was constitutive, and the most potent promoters gave high protein production with levels comparable to those of native rRNA promoters, and production of PepN protein corresponding to approximately 10-15 % of the total cellular protein. High correlation was obtained between the activities of promoters when tested in L. sakei and L. plantarum, which indicates the potential of the SPL for other Lactobacillus species. The SPL enables fine-tuning of stable gene expression for various applications in L. plantarum.
Genetics and epigenetics of eating disorders (2015)

Abstract: Eating disorders (EDs) are serious psychiatric conditions influenced by biological, psychological, and sociocultural factors. A better understanding of the genetics of these complex traits and the development of more sophisticated molecular biology tools have advanced our understanding of the etiology of EDs. The aim of this review is to critically evaluate the literature on the genetic research conducted on three major EDs: anorexia nervosa, bulimia nervosa, and binge eating disorder. We will first review the diagnostic criteria, clinical features, prevalence, and prognosis of anorexia nervosa, bulimia nervosa, and binge eating disorder, followed by a review of family, twin, and adoption studies. We then review the history of genetic studies of EDs covering linkage analysis, candidate-gene association studies, genome-wide association studies, and the study of rare variants in EDs. Our review also incorporates a translational perspective by covering animal models of ED-related phenotypes. Finally, we review the nascent field of epigenetics of EDs and a look forward to future directions for ED genetic research. Keywords: anorexia nervosa, binge eating disorder, bulimia nervosa, animal models, genome-wide association studies, high-throughput sequencing
Polarization-multiplexed and phase-stepped fibre optic shearography using laser wavelength modulation (2000)

A shearography system that measures the deformation gradient using two orthogonal shear directions and performs phase stepping, using no moving mechanical components and a single CCD camera, is described. The light exiting from a highly linearly birefringent optical fibre is switched between two orthogonal linearly polarized states by tuning the optical wavelength of a laser diode via injection current modulation. A polarization sensitive Michelson interferometer is used to shear the image in orthogonal directions for p- and s-polarized light. The change in the optical wavelength is also used to provide a phase step in the pathlength imbalanced interferometer. In this way wavelength modulation of a laser diode source is used to accomplish simultaneously polarization multiplexing and phase stepping in the shearing interferometer. By carefully matching the optical wavelength shift, the optical fibre length and the pathlength imbalance in the interferometer, the π/2 polarization shift can be matched to the required phase step.
Positive Surgical Margins in Soft Tissue Following Radical Cystectomy for Bladder Cancer and Cancer Specific Survival (2007)

Risk factors for positive soft tissue surgical margins are female gender, locally advanced cancer, presence of vascular invasion and mixed histology. Patients with positive soft tissue surgical margins have poor prognosis, and positive soft tissue surgical margins were found to be independently associated with disease specific death.
Abnormally short serum half‐lives of IgG in β2‐microglobulin‐deficient mice (1996)

The MHC class I-related receptor, FcRn, mediates the transfer of maternal gamma globulin (IgG) to young rodents, primarily via intestinal transcytosis, and this provides humoral immunity for the first few weeks after birth. In a previous study, the site of mouse IgG1 (mIgG1) with which FcRn interacts has been mapped using recombinant wild-type and mutated Fc-hinge fragments. The site encompasses residues at the CH2-CH3 domain interface of Fc (Ile253, His310, Gln311, His433 and Asn434) and the same amino acids are involved in regulating the pharmacokinetics of the Fc-hinge fragments. This suggests that in addition to its known function, FcRn might also play a role in IgG homeostasis. Consistent with this hypothesis, in this study, we demonstrate that FcRn alpha-chain mRNA is present not only in neonatal brush border but also in other tissues of adult animals (liver, lung, spleen and endothelial cells). In addition, analysis of the pharmacokinetics of mouse Ig/Fc-hinge fragments in genetically manipulated mice that are deficient in the expression of FcRn demonstrates that the beta-phase half-lives are abnormally short. These findings suggest that FcRn is involved in IgG homeostasis.
Understanding the Search for Meaning in Life: Personality, Cognitive Style, and the Dynamic Between Seeking and Experiencing Meaning (2008)

Although several theories assert that understanding the search for meaning in life is important, empirical research on this construct is sparse. Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program. Assessed were relations between search for meaning and well-being, cognitive style, and the Big Five, Big Three, Approach/Avoidance, and Interest models of personality, with a particular emphasis on understanding the correlates of search for meaning that are independent of presence of meaning. Conceptual models of the relation between search and presence were tested. Findings suggest that people lacking meaning search for it; the search for meaning did not appear to lead to its presence. Study 3 found that basic motive dispositions moderated relations between search for meaning and its presence. Results highlight the importance of basic personality dispositions in understanding the search for meaning and its correlates.
Suppression of bcr‐abl synthesis by siRNAs or tyrosine kinase activity by Glivec alters different oncogenes, apoptotic/antiapoptotic genes and cell proliferation factors (microarray study) (2004)

Short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) were designed to target bcr-abl mRNA in chronic myelogenous leukemia. The ds/siRNAs were transfected into bcr-abl-positive K-562 (derived from blast crisis chronic myelogenous leukemia), using lipofectamine. Penetrating of ds/siRNAs into the cells was detected by fluorescent confocal microscopy, using fluorescein-labeled ds/siRNAs. The cells were treated with mix of three siRNA sequences (3 x 60 nM) during 6 days with three repetitive transfections. The siRNA-treatment was accompanied with significant reduction of bcr-abl mRNA, p210, protein tyrosine kinase activity and cell proliferation index. Treatment of cells with Glivec (during 8 days with four repetitive doses, 180 nM single dose) resulted in analogous reduction of cell proliferation activity, stronger suppression of protein tyrosine kinase activity, and very low reduction of p210. siRNA-mix and Glivec did not affect significantly the viability of normal lymphocytes. Microarray analysis of siRNA- and Glivec-treated K-562 cells demonstrated that both pathways of bcr-abl suppression were accompanied with overexpression and suppression of many different oncogenes, apoptotic/antiapoptotic and cell proliferation factors. The following genes of interest were found to decrease in relatively equal degree in both siRNA- and Glivec-treated cells: Bcd orf1 and orf2 proto-oncogene, chromatin-specific transcription elongation factor FACT 140-kDa subunit mRNA, gene encoding splicing factor SF1, and mRNA for Tec protein tyrosine kinase. siRNA-mix and Glivec provoked overexpression of the following common genes: c-jun proto-oncogene, protein kinase C-alpha, pvt-1 oncogene homologue (myc activator), interleukin-6, 1-8D gene from interferon-inducible gene family, tumor necrosis factor receptor superfamily (10b), and STAT-induced STAT inhibitor.