gebhart/patrepeval huggingface dataset:
Selection of initiation sites by eucaryotic ribosomes: effect of inserting AUG triplets upstream from the coding sequence for preproinsulin (1984)

Recombinant plasmids that direct synthesis of rat preproinsulin under the direction of the SV40 early promoter have been used to probe the mechanism of initiation of translation. Insertion of an upstream AUG triplet that was out-of-frame with respect to the coding sequence for preproinsulin reduced the yield of proinsulin, in keeping with the predictions of the scanning model. The extent to which an upstream AUG codon interfered depended on sequences surrounding the AUG triplet; with two constructs ( p255 /20 and C2) the 5'-proximal AUG codon constituted an absolute barrier: there was no initiation at the downstream start site for preproinsulin. With two other constructs ( p255 /9, p255 /21), however, proinsulin was made despite the presence of an upstream, out-of-frame AUG codon in a favorable context for initiation. In those cases the reading frame set by the first AUG triplet was short, terminating before the start of the preproinsulin coding sequence. The interpretation that ribosomes initiate at the first AUG, terminate, and then reinitiate at the AUG that directly precedes the preproinsulin coding sequence was tested by introducing a point mutation that eliminated the terminator codon: the resulting mutant made no proinsulin.
Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ (2002)

Low-density lipoprotein (LDL) and its oxidized derivatives are hypothesized to impair vascular function by increasing superoxide anion (O.). To investigate mechanisms in situ, isolated carotid arteries were incubated with native LDL (nLDL) or minimally oxidized LDL (mmLDL). With the use of en face fluorescent confocal microscopy and hydroethidine, an oxidant-sensitive fluorescent probe, we found that nLDL increased O. in vascular endothelium greater than fourfold by an N(omega)-nitro-L-arginine methyl ester (L-NAME)-inhibitable mechanism. In contrast, mmLDL increased O. in vascular endothelium greater than eightfold by mechanisms that were partially inhibited by L-NAME and allopurinol and essentially ablated by diphenyleneiodium. These data indicate that both nLDL and mmLDL uncouple endothelial nitric oxide synthase (eNOS) activity and that mmLDL also activates xanthine oxidase and NADPH oxidoreductase to induce greater increases in O. generation than nLDL. Western analysis revealed that both lipoproteins inhibited A-23187-stimulated association of heat shock protein 90 (HSP90) with eNOS without inhibiting phosphorylation of eNOS at serine-1179 (phospho-eNOS), an immunological index of electron flow through the enzyme. As HSP90 mediates the balance of.NO and O. generation by eNOS, these data provide new insight into the mechanisms by which oxidative stress, induced by nLDL and mmLDL, uncouple eNOS activity to increase endothelial O. generation.
Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus (1990)

Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.
Session Initiation Protocol (SIP) Extension Header Field for Registering Non-Adjacent Contacts (2002)

The REGISTER function is used in a Session Initiation Protocol (SIP) system primarily to associate a temporary contact address with an address-of-record. This contact is generally in the form of a Uniform Resource Identifier (URI), such as Contact: and is generally dynamic and associated with the IP address or hostname of the SIP User Agent (UA). The problem is that network topology may have one or more SIP proxies between the UA and the registrar, such that any request traveling from the user's home network to the registered UA must traverse these proxies. The REGISTER method does not give us a mechanism to discover and record this sequence of proxies in the registrar for future use. This document defines an extension header field, Path which provides such a mechanism.
A Probabilistic Framework for Answer Selection in Question Answering (2007)

This paper describes a probabilistic answer selection framework for question answering. In contrast with previous work using individual resources such as ontologies and the Web to validate answer candidates, our work focuses on developing a unified framework that not only uses multiple resources for validating answer candidates, but also considers evidence of similarity among answer candidates in order to boost the ranking of the correct answer. This framework has been used to select answers from candidates generated by four different answer extraction methods. An extensive set of empirical results based on TREC factoid questions demonstrates the effectiveness of the unified framework. 1
Reconfigurable FPGA Accelerator for Databases (2012)

Database management systems have traditionally been implemented entirely in software. However, adding hardware to database cluster servers to gain more speed has its price. Firstly, the cost of the hardware itself, secondly the increased power consumption from the numerous processors that have to be used. \n\nThe purpose of this study is to investigate how partial run-time reconfiguration in FPGAs can be used to accelerate databases. It aims to show how an FPGA based query processor can work in collaboration with a regular software database to accelerate certain queries.\n\nThis thesis proposes a novel way of using dynamic partial reconfiguration in FPGAs to process arbitrary queries in hardware. We investigate how SQL queries can be decomposed and turned into hardware modules that are 'stitched' together at run-time to form a stream processing datapath. Consequently, a set of customizable hardware modules that each can implement a range of SQL operators are presented. In addition, the thesis gives a method for floorplanning a high capacity FPGA for slot based partial reconfiguration.\n\nIn the end, by the help of a case study we can conclude that the main bottleneck is the interface to the host computer. Another interesting finding is that unlike conventional databases, the accelerator is not slowed down by a more complex query. On the contrary, filtering out results actually speeds it up.
Colorectal cancer statistics, 2014 (2014)

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in men and women in the United States. This article provides an overview of colorectal cancer statistics, including the most current data on incidence, survival, and mortality rates and trends. Incidence data were provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results program and the North American Association of Central Cancer Registries. Mortality data were provided by the National Center for Health Statistics. In 2014, an estimated 71,830 men and 65,000 women will be diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease. Greater than one-third of all deaths (29% in men and 43% in women) will occur in individuals aged 80 years and older. There is substantial variation in tumor location by age. For example, 26% of colorectal cancers in women aged younger than 50 years occur in the proximal colon, compared with 56% of cases in women aged 80 years and older. Incidence and death rates are highest in blacks and lowest in Asians/Pacific Islanders; among males during 2006 through 2010, death rates in blacks (29.4 per 100,000 population) were more than double those in Asians/Pacific Islanders (13.1) and 50% higher than those in non-Hispanic whites (19.2). Overall, incidence rates decreased by approximately 3% per year during the past decade (2001-2010). Notably, the largest drops occurred in adults aged 65 and older. For instance, rates for tumors located in the distal colon decreased by more than 5% per year. In contrast, rates increased during this time period among adults younger than 50 years. Colorectal cancer death rates declined by approximately 2% per year during the 1990s and by approximately 3% per year during the past decade. Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations.
Competition of congo red and thioflavin S binding to amyloid sites in alzheimer's diseased tissue (1995)

Abstract Though the strong affinity of Congo red and thioflavin S for amyloid deposits has been known for a long time, the binding mechanism of these biological dyes to amyloid sites is still not understood. In the present work, the competition of these two dyes for binding in Alzheimer amyloid is investigated. Analyses by optical microscopy and microspectrofluorimetry were performed on several series of stained diseased brain sections. Microspectrofluorimetric analyses showed that bound Congo red and bound thioflavin S have characteristic spectra in which the fluorescence maxima are distinct of those for the free dyes. Both, optical microscopic analyses and fluorescence measurements of stained brain sections indicated that Congo red and thioflavin S compete with each other at the same interacting site on diseased cerebral tissue. The staining efficiency of the replacing dye seems to be a maximum for a concentration of about 1%. © 1995 John Wiley &amp; Sons, Inc.
Maltohexaose-Producing Amylase of Bacillus circulans F—2 (1991)

Bacillus circulans F-2 produces an alpha-amylase which has a potent starch granule-digesting activity and produces maltohexaose from soluble starch. Action pattern of this amylase was examined in detail. When non-reducing end-labelled amylopectin was subjected to enzymatic hydrolysis, radioactivity was released rapidly. During enzymatic hydrolysis of amylopectin, intermediate size products were not detected on gel filtration. Relationship between decrease in iodine staining and increase in reducing value during the enzymatic hydrolysis of amylopectin was plotted. The amylase gave a steadily declining line which is very close to that obtained with beta-amylase while alpha-amylase gave a rapidly declining one. The amylase produced labelled glucose, maltose and maltotriose from reducing end-labelled maltoheptaose, -octaose and -nonaose, respectively. The anomeric configuration of produced maltohexaose and maltotetraose was found to be alpha. This amylase was classified as a member of unique alpha-amylases which act in an exo-manner but produce saccharides with alpha configuration.
Pulmonary and Oxygen Transport Effects of Intravenously Administered Endotoxin in Normal Humans (1992)

Little data are available describing the initial changes in pulmonary function and oxygen transport during human endotoxemia. We studied 26 normal humans after intravenously administered endotoxin (4 ng/kg). To evaluate alterations in gas exchange, hemodynamic monitoring was performed in nine subjects given endotoxin and six subjects given saline only. Compared with the control subjects, no changes in gas exchange occurred at 3 h, but after volume loading (mean, 2.2 L saline infused from 3 to 5 h) the PaO2 fell (86.1 +/- 2.3 mm Hg, p = 0.042), and the AaPO2 widened (18.5 +/- 1.7 mm Hg, p = 0.005). Oxygen consumption and delivery both increased significantly at 3 h (219 +/- 17 and 1,030 +/- 43 ml/min.min2) and 5 h (203 +/- 7 and 949 +/- 48 ml/min.min2) (p less than or equal to 0.035), whereas oxygen extraction fell at 3 h (p = 0.041). Seventeen subjects underwent bronchoalveolar lavage 14 +/- 4 days before and at 1.5 to 3 h (n = 8) or 5 h after (n = 9) the administration of endotoxin. No increase in the total number of cells or percent or absolute number of neutrophils was found at either time point. The rate of clearance of inhaled 99mTc-diethylenetriamine pentacetate aerosol, a measure of alveolar epithelial permeability, increased in subjects scanned before 3 h (n = 8; p less than 0.05), whereas no significant changes occurred in subjects scanned 5 h after endotoxin (n = 5) or in control subjects (n = 6). Early inflammatory responses after intravenous administration of endotoxin to normal humans results in alterations in gas exchange and lung permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes self-adjustment by a computerized program--first experiences in inpatient and outpatient treatment. (1985)

Blood glucose self-monitoring is essential to stabilize diabetes on a normoglycemic level. However, patients often do not find the correct insulin adaptation. Therefore, we developed a computer system to adapt insulin doses using a control matrix. During a first inpatient and outpatient period, we attained a very satisfactory blood glucose normalization and stabilization. During the outpatient period the HbA1c values decreased. Stopping the program in some patients blood glucose levels and HbA1c values increased again.
Central Infusion of Histamine Reduces Fat Accumulation and Upregulates UCP Family in Leptin-Resistant Obese Mice (2001)

Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice. Infusion of histamine (0.05 pmol x g body wt(-1) x day(-1)) into the lateral cerebroventricle (i.c.v.) for 7 successive days reduced food intake and body weight significantly in both diet-induced obesity (DIO) and db/db mice. Histamine treatment reduced body fat weight, ob gene expression, and serum leptin concentration more in the model mice than in pair-fed controls. The suppressive effect on fat deposition was significant in visceral fat but not in subcutaneous fat. Serum concentrations of glucose and/or insulin were reduced, and tests for glucose and insulin tolerance showed improvement of insulin sensitivity in those mice treated with histamine compared with pair-fed controls. On the other hand, gene expression of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 expression in white adipose tissue were upregulated more in mice with i.c.v. histamine infusion than in the pair-fed controls. These upregulating effects of histamine were attenuated by targeted disruption of the H1-receptor in DIO and db/db mice. Sustained i.c.v. treatment with histamine thus makes it possible to partially restore the distorted energy intake and expenditure in leptin-resistant mice. Together, i.c.v. treatment with histamine contributes to improvement of energy balance even in leptin-resistant DIO and db/db mice.
Importance of the cytochrome P450 monooxygenase CYP52 family for the sophorolipid-producing yeast Candida bombicola (2010)

Three cytochrome P450 monooxygenases belonging to the CYP52 family were isolated from the genome of the sophorolipid-producing yeast Candida bombicola using degenerate PCR and genomic walking. One gene displayed high identity with the CYP52E members and was classified into this group (CYP52E3), whereas the other genes belonged to new groups: CYP52M and CYP52N. CYP52E3 and CYP52N1 turned out to be of no relevance for sophorolipid production, but show clear upregulation when the yeast cells are grown on alkanes as the sole carbon source. On the other hand, CYP52M1 is clearly upregulated during sophorolipid synthesis and very likely takes part in sophorolipid formation.
Novel amidine-containing peptidyl phosphonates as irreversible inhibitors for blood coagulation and related serine proteases (1994)

A series of new peptidyl (alpha-aminoalkyl)phosphonate diphenyl esters containing the 4-amidinophenyl group were synthesized and tested as irreversible inhibitors for thrombin and other trypsin-like enzymes. These phosphonates irreversibly inhibited several coagulation enzymes and trypsin. Boc-D-Phe-Pro-(4-AmPhGly)P(OPh)2 is the best human thrombin inhibitor in the series with a k(obs)/[I] value of 11,000 M-1 s-1, and it inhibits thrombin more than 5-fold more effectively than the other enzymes tested. Z-(4-AmPhGly)P(OPh)2 is the best inhibitor for plasma kallikrein with a k(obs)/[I] value of 18,000 M-1 s-1. Generally, the (4-AmPhGly)P(OPh)2 derivatives are better inhibitors of thrombin and trypsin than the corresponding (4-AmPhe)P(OPh)2 derivatives which contain an extra CH2 separating the amidinophenyl group from the peptide backbone. The amidino phosphonates did not inhibit acetylcholinesterase and were chemically stable in neutral buffers. In addition, the inhibited trypsin derivative did not regain any enzyme activity after removal of excess inhibitor and incubation in a pH 7.5 buffer for 1 day. Boc-D-Phe-Pro-(4-AmPhGly)P(OPh)2 and D-Phe-Pro-(4-AmPhe)P(OPh)2 prolonged the prothrombin time ca. 2-fold and prolonged the activated partial thromboplastin time ca. 3-4-fold in human plasma at concentrations of 63 and 125 microM, respectively. The novel amidine-containing peptidyl phosphonates reported here are thus effective anticoagulants in vitro, and they may have utility for use in vivo.
Phase Variation in Helicobacter pylori Lipopolysaccharide (1998)

Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigen Lewis x (Le(x)) in a polymeric form. Le(x) is beta-D-galactose-(1-4)-[alpha-L-fucose-(1-3)]-beta-D-acetylglucosamine. Schematically the LPS structure is (Le(x))n-core-lipid A. In this report, we show that Le(x) expression is not a stable trait but that LPS displays a high frequency (0.2 to 0.5%) of phase variation, resulting in the presence of several LPS variants in one bacterial cell population. One type of phase variation implied the loss of alpha1,3-linked fucose, resulting in variants that expressed nonsubstituted polylactosamines (also called the i antigen), i.e., Le(x) minus fucose; LPS: (lactosamine)n-core-lipid A. The switch of Le(x) to i antigen was reversible. A second group of variants arose by loss of polymeric main chain which resulted in expression of monomeric Le(y); LPS: (Le(y))-core-lipid A. A third group of variants arose by acquisition of alpha1,2-linked fucose which hence expressed Le(x) plus Le(y); LPS: (Le(y))(Le(x))n-core-lipid A. The second and third group of variants switched back to the parental phenotype [(Le(x))-core-lipid A] in lower frequencies. Part of the variation can be ascribed to altered expression levels of glycosyltransferase levels as assessed by assaying the activities of galactosyl-, fucosyl-, and N-acetylglucosaminyltransferases. Clearly phase variation increases the heterogeneity of H. pylori, and this process may be involved in generating the very closely related yet genetically slightly different strains that have been isolated from one patient.
Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations (2015)

Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution.
Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion. (1991)

The molecular mechanism by which interleukin (IL)-1 inhibits insulin secretion and ultimately causes destruction of the pancreatic beta-cell remains unknown. Evidence is presented which suggests that IL-1 beta-induced inhibition of insulin secretion is dependent on the metabolism of L-arginine to nitric oxide. NG-Monomethylarginine, a competitive inhibitor of the L-arginine-dependent enzyme nitric oxide synthase, completely prevents IL-1-induced inhibition of glucose-stimulated insulin secretion as well as nitrite production by islets. It is further shown that IL-1 beta induces nitric oxide formation in islets as evidenced by an electron paramagnetic resonance feature at g = 2.04 which is similar to previously reported iron-nitrosyl complexes formed from the destruction of iron-sulfur centers by nitric oxide. Inhibition of the nitric oxide synthase by NG-monomethylarginine completely prevents the formation of this EPR signal in islets. These results show that IL-1-induced inhibition of insulin secretion is mediated through formation of nitric oxide and suggest that the generation of nitric oxide may represent the cellular mechanism responsible for beta-cell destruction.