gebhart/patrepeval huggingface dataset:
Biological Characterization of Two Novel Cathelicidin-derived Peptides and Identification of Structural Requirements for Their Antimicrobial and Cell Lytic Activities (1996)

Cathelicidins are a family of myeloid antimicrobial peptide precursors that have been identified in several mammalian species (Zanetti, M., Gennaro, R., and Romeo, D. (1995) FEBS Lett. 374, 1-5). Two novel bovine congeners have been deduced from cDNA. Their C-terminal sequences of 27 and 28 residues correspond to putative antimicrobial peptides with a cationic N-terminal region predicted to assume an amphipathic alpha-helical conformation followed by a hydrophobic C-terminal tail. Peptides corresponding to these sequences have been chemically synthesized and shown to exert a potent antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, and fungi. Both peptides are also cytotoxic to human erythrocytes and neutrophils, although at higher than microbicidal concentrations. The target selectivity has been improved by synthesizing truncated analogues, comprising only the 18 N-terminal residues, which show a great reduction in cytotoxic, but not in antimicrobial activity. The involvement of the C-terminal hydrophobic tail in the cytotoxic activity has been further demonstrated by inducing a major loss of activity in an analogue after replacing highly hydrophobic residues with more hydrophilic ones.
Conformational Dynamics in the Acyl-CoA Synthetases, Adenylation Domains of Non-ribosomal Peptide Synthetases, and Firefly Luciferase (2009)

The ANL superfamily of adenylating enzymes contains acyl- and aryl-CoA synthetases, firefly luciferase, and the adenylation domains of the modular non-ribosomal peptide synthetases (NRPSs). Members of this family catalyze two partial reactions: the initial adenylation of a carboxylate to form an acyl-AMP intermediate, followed by a second partial reaction, most commonly the formation of a thioester. Recent biochemical and structural evidence has been presented that supports the use by this enzyme family of a remarkable catalytic strategy for the two catalytic steps. The enzymes use a 140 degrees domain rotation to present opposing faces of the dynamic C-terminal domain to the active site for the different partial reactions. Support for this domain alternation strategy is presented along with an explanation of the advantage of this catalytic strategy for the reaction catalyzed by the ANL enzymes. Finally, the ramifications of this domain rotation in the catalytic cycle of the modular NRPS enzymes are discussed.
Adenosine A2Areceptors and depression (2003)

Adenosine and its analogues have been shown to induce "behavioral despair" in animal models believed to be relevant to depression. Recent data have shown that selective adenosine A2A receptor antagonists (e.g., SCH 58261, ZM241385, and KW6002) or genetic inactivation of the receptor was effective in reversing signs of behavioral despair in the tail suspension and forced swim tests, two screening procedures predictive of antidepressant activity. A2A antagonists were active in the tail suspension test using either mice previously screened for having high immobility scores or mice that were selectively bred for their spontaneous "helplessness" in this test. At stimulant doses, caffeine, a nonselective A1/A2A receptor antagonist, was effective in the forced swim test. The authors have hypothesized that the antidepressant-like effect of selective A2A antagonists is linked to an interaction with dopaminergic transmission, possibly in the frontal cortex. In support of this idea, administration of the dopamine D2 receptor antagonist haloperidol prevented antidepressant-like effects elicited by SCH 58261 in the forced swim test (putatively involving cortex), whereas it had no effect on stimulant motor effects of SCH 58261 (putatively linked to ventral striatum). The interaction profile of caffeine with haloperidol differed markedly from that of SCH 58261 in the forced swim and motor activity tests. Therefore, a clear-cut antidepressant-like effect could not be ascribed to caffeine. In conclusion, available data support the proposition that a selective blockade of the adenosine A2A receptor may be an interesting target for the development of effective antidepressant agents.
Arrestin‐Mediated Endocytosis of Yeast Plasma Membrane Transporters (2009)

Many plasma membrane transporters in yeast are endocytosed in response to excess substrate or certain stresses and degraded in the vacuole. Endocytosis invariably requires ubiquitination by the HECT domain ligase Rsp5. In the cases of the manganese transporter Smf1 and the amino acid transporters Can1, Lyp1 and Mup1 it has been shown that ubiquitination is mediated by arrestin-like adaptor proteins that bind to Rsp5 and recognize specific transporters. As yeast contains a large family of arrestins, this has been suggested as a general model for transporter regulation; however, analysis is complicated by redundancy amongst the arrestins. We have tested this model by removing all the arrestins and examining the requirements for endocytosis of four more transporters, Itr1 (inositol), Hxt6 (glucose), Fur4 (uracil) and Tat2 (tryptophan). This reveals functions for the arrestins Art5/Ygr068c and Art4/Rod1, and additional roles for Art1/Ldb19, Art2/Ecm21 and Art8/Csr2. It also reveals functional redundancy between arrestins and the arrestin-like adaptors Bul1 and Bul2. In addition, we show that delivery to the vacuole often requires multiple additional ubiquitin ligases or adaptors, including the RING domain ligase Pib1, and the adaptors Bsd2, Ear1 and Ssh4, some acting redundantly. We discuss the similarities and differences in the requirements for regulation of different transporters.
A prospective study of cancer incidence in a cohort examined for allergy (1995)

In order to assess the association between atopy and cancer risk, a cohort of 6593 skin-prick-tested patients was established. Among atopic subjects, no overall increased cancer risk was found, but the incidence of both breast cancer (standardized incidence ratio (SIR) 2.50, 95% CI 1.01-5.16) and malignant lymphomas (SIR 4.40, 95% CI 1.20-11.3) was significantly enhanced. Atopic subjects with asthma showed a decreased overall cancer risk (SIR 0.73, 95% CI 0.27-1.60), as compared with the other asthmatic subjects (SIR 1.46, 95% CI 1.03-2.04). The cancer risk for subjects with rhinitis was near unity (SIR 1.11), irrespective of whether the subjects were atopic or not. An almost significant risk increase for cancer was observed among subjects with urticaria (SIR 1.70, 95% CI 0.99-2.80). Our results support neither the original hypothesis of an overall cancer protective effect of atopy, nor that of an opposite effect; rather, they strengthen the view that the association between atopic diseases and cancer is complex.
Insulin gene mutations and diabetes (2011)

Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half-life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four types have been identified: (i) proinsulin Providence (H34D); (ii) proinsulin Tokyo (R89H); (iii) proinsulin Kyoto (R89L); and (iv) proinsulin Oxford (R89P). Three of these are processing site mutations. The mutation of proinsulin Providence, in contrast, is thought to cause sorting abnormality. Compared with normal proinsulin, a significant amount of proinsulin Providence enters the constitutive pathway where processing does not occur. These insulin gene mutations with hyper(pro)insulinemia were very rare, showed only mild diabetes or glucose intolerance, and hyper(pro)insulinemia was the key for their diagnosis. However, this situation changed dramatically after the identification of insulin gene mutations as a cause of neonatal diabetes. This class of insulin gene mutations does not show hyper(pro)insulinemia. Mutations at the cysteine residue or creating a new cysteine will disturb the correct disulfide bonding and proper conformation, and finally will lead to misfolded proinsulin accumulation, endoplasmic reticulum stress and apoptosis of pancreatic β-cells. Maturity-onset diabetes of the young (MODY) or an autoantibody-negative type 1-like phenotype has also been reported. Very recently, recessive mutations with reduced insulin biosynthesis have been reported. The importance of insulin gene mutation in the pathogenesis of diabetes will increase a great deal and give us a new understanding of β-cell biology and diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00100.x, 2011).
Foamed acidizing and selective diverting using stable foam for improved acid stimulation (1978)

Foamed stimulation has been broadened to include the use of high- and low-quality (30 to 75% nitrogen) foams for acidizing soluble formations. To insure correct placement of foamed acidizing systems, foamed diverting techniques using high-quality (80 to 90% nitrogen) foamed water systems currently are being employed in several W. Texas and SE. New Mexico areas. Application of these techniques has been successful in both producing and injection wells. The mechanics of these systems is discussed along with comparative results and current cost economics. (20 refs.)
Human Neural Stem Cells Over-Expressing VEGF Provide Neuroprotection, Angiogenesis and Functional Recovery in Mouse Stroke Model (2007)

Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.
Genetic regulation of stem cell origins in the mouse embryo (2005)

'Stem cell' has practically become a household term, but what is a stem cell and where does it come from? Insight into these questions has come from the early mouse embryo, or blastocyst, from which three kinds of stem cells have been derived: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extraembryonic endoderm (XEN) cells. These stem cells appear to derive from three distinct tissue lineages within the blastocyst: the epiblast, the trophectoderm, and the extraembryonic endoderm. Understanding how these lineages arise during development will illuminate efforts to understand the establishment and maintenance of the stem cell state and the mechanisms that restrict stem cell potency. Genetic analysis has enabled the identification of several genes important for lineage decisions in the mouse blastocyst. Among these, Oct4, Nanog, Cdx2, and Gata6 encode transcription factors required for the three lineages of the blastocyst and for the maintenance their respective stem cell types. Interestingly, genetic manipulation of several of these factors can cause lineage switching among these stem cells, suggesting that knowledge of key lineage-determining genes could help control differentiation of stem cells more generally. Pluripotent stem cells have also been isolated from the human blastocyst, but the relationship between these cells and stem cells of the mouse blastocyst remains to be explored. This review describes the genetic regulation of lineage allocation during blastocyst formation and discusses similarities and differences between mouse and human ES cells.
Functional role of alpha-calcitonin gene-related peptide in the regulation of the cardiovascular system. (2001)

It remains unknown whether the extent of vasoactive response to exogenous calcitonin gene-related peptide (CGRP) varies among different regional vascular beds. It is also unclear whether endogenous CGRP plays a functional role in regulating basal vascular activity. To address these two issues, experiments were conducted in 27 anesthetized rats instrumented with a carotid flow probe and catheters in a jugular vein, left ventricle (LV), and femoral artery, and in 6 conscious dogs, chronically instrumented with LV pressure gauge, aortic and atrial catheters, and ascending aortic, coronary, carotid, and renal flow probes. In both species, administration of human alpha-CGRP (0.1-0.5 microg/kg, i.v.) induced a dose-dependent peripheral vasodilation that was completely abolished by pretreatment with alpha-CGRP[8-37] (30 microg/kg/min, i.v.), a competitive antagonist of CGRP receptors. Regional blood flow measured by the radioactive microsphere technique in rats showed that the alpha-CGRP (0.3 microg/kg, i.v.)-induced increase in blood flow was greater (p < 0.05) in the heart (+53 +/- 16%) than in the brain (+14 +/- 6%). In the presence of beta-adrenergic receptor blockade with propranolol, however, the increases in blood flow in these two vascular beds were identical. In conscious dogs, alpha-CGRP (0.3 microg/kg, i.v.) produced similar increases in coronary (+24 +/- 6%), carotid (+26 +/- 3%), and renal (+26 +/- 6%) blood flow, which were different from the patterns induced by other vasodilators; at an equivalent level of reduction in mean arterial pressure and total peripheral resistance, alpha-CGRP increased coronary and carotid blood flow significantly less (p < 0.05) than adenosine or nitroprusside. Unlike alpha-CGRP, adenosine and nitroprusside, as expected, induced pronounced differential blood flow changes in these vascular beds. Neither systemic hemodynamics nor regional blood flow distribution was altered by the administration of a pharmacological blocking dose of alpha-CGRP[8-37] in the two species. Thus, we conclude that endogenous alpha-CGRP does not play an important role in cardiovascular regulation under normal, resting conditions, although exogenous alpha-CGRP induces a marked, comparable vasorelaxation in different regional vascular beds.
[Mechanism study of electrothrombosis by copper needle]. (2001)

Dissociation of copper ion and agglutination of RBC are the basic principle of electrothrombosis with copper needle. A 4V direct current and 17.5 minutes are the safe and effective conditions for thrombus formation in the blood vessels.
Full-wave analysis of choking characteristics of sleeve balun on coaxial cables (2002)

An optimal design for a sleeve balun with maximum choking on a coaxial cable is determined using a full-wave body of revolution finite difference time domain method with perfectly matched layer boundary conditions. An analysis of the sensitivity of choke length L and outer diameter R2 on choking effectiveness was carried out. A balun with L=77.5 mm (0.232λ0) and R2=8 mm on a cable with R1=2 mm (R2/R1=4) results in an S21 of −20 dB at 900 MHz and −15.5 dB at 2730 MHz. The isolation of the balun at 900 MHz is quickly degraded as the R2/R1 ratio is reduced below 2. Increasing R2/R1 to 8, results in a reduction of optimum balun length L to approximately 0.215λ0 , approximately 14% shorter than the typical recommended length for an ‘ideal’ quarter-wave balun.
Uses ofX‐Ray Powder Diffraction In the Pharmaceutical Industry (2010)

Abstract X‐ray diffraction (XRD) has a broad range of applications in various stages of drug development and manufacturing, such as API characterization and identification. API characterization is more commonly applied during drug development while API identification is directed more towards manufacturing, regulatory aspects, and intellectual property. This article focuses on basic principles and experimental procedures of XRD and its application in API characterization and identification.
Development of a Method for Rapid Quantitation of Amino Acids by Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) in Plasma (2000)

A new analytical method has been developed and is proposed for the rapid determination of eighteen common amino acids, including tryptophan, in plasma and dried blood spots, by liquid chromatography coupled with ionspray tandem mass spectrometry. Potentially the method can include other amino acids and can be used for the diagnosis of metabolic disease. The use of the ionspray tandem mass spectrometry approach permits extremely rapid chromatographic separation of all amino acids requiring less than four minutes for the analysis of each sample, after a simple sample preparation procedure. The chromatographic separation of the analytes was achieved using a CN normal phase column and a water/acetonitrile/trifluoroacetic acid mobile phase at flow rate of 1 ml/min. The mass spectrometer was operated in multiple reaction monitoring mode, where each analyte had its own unique precursor and product ion setting. The quantitative analysis of amino acids was achieved using as internal standards just two representative isotopically labeled amino acids: D4-Ala and D5-Phe. Calibration is made externally by using aqueous solutions with the same labelled amino acids as internal standards. The high specificity of tandem mass spectrometry coupled with a fast chromatographic process is suitable for the rapid and reliable assay of metabolically significant amino acids. The liquid chromatography-tandem mass spectrometry method is more effective than other published tandem mass spectrometry methods at distinguishing isobaric amino acids like Leu, Ile and HO-Pro and certainly far more rapid than HPLC or ion-exchange chromatographic methods.
Catch-bond mechanism of the bacterial adhesin FimH (2016)

Ligand-receptor interactions that are reinforced by mechanical stress, so-called catch-bonds, play a major role in cell-cell adhesion. They critically contribute to widespread urinary tract infections by pathogenic Escherichia coli strains. These pathogens attach to host epithelia via the adhesin FimH, a two-domain protein at the tip of type I pili recognizing terminal mannoses on epithelial glycoproteins. Here we establish peptide-complemented FimH as a model system for fimbrial FimH function. We reveal a three-state mechanism of FimH catch-bond formation based on crystal structures of all states, kinetic analysis of ligand interaction and molecular dynamics simulations. In the absence of tensile force, the FimH pilin domain allosterically accelerates spontaneous ligand dissociation from the FimH lectin domain by 100,000-fold, resulting in weak affinity. Separation of the FimH domains under stress abolishes allosteric interplay and increases the affinity of the lectin domain. Cell tracking demonstrates that rapid ligand dissociation from FimH supports motility of piliated E. coli on mannosylated surfaces in the absence of shear force.
Real‐time PCR quantification of haematopoietic chimerism after transplantation: a comparison between TaqMan and hybridization probes technologies (2009)

Summary This study aimed to compare the sensitivity and accuracy of two methods of quantitative real‐time polymerase chain reaction (qrt‐PCR), in order to determine haematopoietic chimerism (CH): single nucleotide polymorphisms using TaqMan (TM) probes and insertion/deletion polymorphisms using Hybridization (Hyb) probes. A total of 106 samples from 20 patients who underwent allogenic stem cell transplantation ( n = 14) or live‐donor liver transplantation ( n = 6) were studied. The mean level of chimerism was 8.37% for the TM method and 7.73% in the Hyb method, which was not significantly different ( P = 0.69). The Pearson correlation coefficient between the two methods was r = 0.91 ( P &lt; 0.001). The estimation of the regression line, using the Passing and Balbock method was Intercept A −0.0381 [95% confidence interval (CI) −0.1265 to 0.0296) and Slope B: 1.04609(95% CI 0.9349–1.161). Bland–Altman data showed that the standard deviations, which differed between the two methods (%Hyb–%TM), were 0.98 and −1.28. The accuracy and sensitivity of qrt‐PCR chimerism is independent of the method used if the optimization is adequate and satisfies the criteria for adequate study. Real‐time PCR, independent of the method adopted, is a very good tool for study levels of CH.
Role of Phosphorylation in Determining the Backbone Dynamics of the Serine/Threonine-Proline Motif and Pin1 Substrate Recognition (1998)

Proline residues provide a backbone switch in a polypeptide chain, which is controlled by the cis/trans isomerization about the peptidyl-prolyl bond. Phosphorylation of serine- and threonine-proline motifs has been shown to be a critical regulatory event for many proteins. The biological significance of these motifs has been further highlighted by the discovery of a novel and essential peptidyl-prolyl cis/trans isomerase Pin1. Pin1 is required for progression through mitosis via catalyzing the isomerization of phosphorylated Ser/Thr-Pro motifs specifically present in mitosis-specific phosphoproteins. However, little is known whether the phosphorylation regulates the conformational switch of the Ser/Thr-Pro bonds. Here, we report the synthesis and conformational characterization of a series of peptides that contain the phosphorylated or nonphosphorylated Ser/Thr-Pro motifs. Phosphorylation affected the rate of the cis to trans isomerization of the Thr/Ser-Pro bonds. As determined by a protease-coupled assay, the isomerization rate of phosphorylated Thr-Pro bond was found to be 8-fold slower than that of the nonphosphorylated analogue. Furthermore, studies of the pH dependence of the isomerization of the phosphopeptides reveal that both cis content and the rate constant of prolyl cis to trans isomerization are lower for the dianionic state of the phosphothreonine-containing peptides. These effects of phosphorylation are specific for phosphorylated Ser/Thr since neither phosphorylated Tyr nor glutamic acid was able to affect the prolyl isomerization. Finally, our experiments provide evidence that effective catalysis of cis/trans isomerization of phosphorylated Ser/Thr-Pro bonds by Pin1 is specific to the dianionic form of the substrate. Thus, our results demonstrate that protein phosphorylation specifically regulates the backbone dynamics of the Ser/Thr-Pro motifs and that Pin1 specifically isomerizes the certain conformation of the phosphorylated Ser/Thr-Pro motifs.
ChemInform Abstract: Matrix Infrared Spectra and Electronic Structure Calculations of the First Actinide Borylene: FB=ThF2. (2010)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Analyzing Argumentative Discourse Units in Online Interactions (2014)

Argument mining of online interactions is in its infancy. One reason is the lack of annotated corpora in this genre. To make progress, we need to develop a principled and scalable way of determining which portions of texts are argumentative and what is the nature of argumentation. We propose a two-tiered approach to achieve this goal and report on several initial stud-ies to assess its potential. 1