gebhart/patrepeval huggingface dataset:
Binding of anti–platelet factor 4/heparin antibodies depends on the thermodynamics of conformational changes in platelet factor 4 (2014)

The chemokine platelet factor 4 (PF4) undergoes conformational changes when complexing with polyanions. This can induce the antibody-mediated adverse drug effect of heparin-induced thrombocytopenia (HIT). Understanding why the endogenous protein PF4 becomes immunogenic when complexing with heparin is important for the development of other negatively charged drugs and may also hint toward more general mechanisms underlying the induction of autoantibodies to other proteins. By circular dichroism spectroscopy, atomic force microscopy, and isothermal titration calorimetry we characterized the interaction of PF4 with unfractionated heparin (UFH), its 16-, 8-, and 6-mer subfractions, low-molecular-weight heparin (LMWH), and the pentasaccharide fondaparinux. To bind anti-PF4/heparin antibodies, PF4/heparin complexes require (1) an increase in PF4 antiparallel β-sheets exceeding ∼30% (achieved by UFH, LMWH, 16-, 8-, 6-mer), (2) formation of multimolecular complexes (UFH, 16-, 8-mer), and (3) energy (needed for a conformational change), which is released by binding of ≥11-mer heparins to PF4, but not by smaller heparins. These findings may help to synthesize safer heparins. Beyond PF4 and HIT, the methods applied in the current study may be relevant to unravel mechanisms making other endogenous proteins more vulnerable to undergo conformational changes with little energy requirement (eg, point mutations and post-translational modifications) and thereby predisposing them to become immunogenic.
Interaction of high density lipoprotein with adipocytes in a new patient with Tangier disease. (1987)

A 56-year-old man, the offspring of a consanguineous first cousin marriage, presented with clinical, morphological, and biochemical features of familial deficiency of high-density lipoproteins (Tangier disease). Of 8 first- and second-degree relatives examined, 4 had either plasma apo A-I or HDL cholesterol concentrations 2 standard deviations below normal population mean on at least 1 occasion. The patient and a majority of his relatives also had high plasma apo B concentrations relative to their levels of cholesterol. Adipose tissue biopsy was undertaken to study HDL interaction with the patients' cells. Specific uptake of HDL3 was demonstrated in adipocytes of this patient, but was decreased relative to a control of similar fat cell size. However, no marked difference in fat cell cholesterol content was observed between the Tangier patient and the control. Thus it appears unlikely that adipocytes play a role in the etiology of Tangier disease.
SMT and SPE machine translation systems for WMT'09 (2009)

This paper describes the development of several machine translation systems for the 2009 WMT shared task evaluation. We only consider the translation between French and English. We describe a statistical system based on the Moses decoder and a statistical post-editing system using SYSTRAN's rule-based system. We also investigated techniques to automatically extract additional bilingual texts from comparable corpora.
A Multi-Agent Based Virtual Personal Assistant for E-Health Service (2013)

The application of Information and Communication Technologies (ICT) in the health sector is increasingly changing today’s health care. A communication agent for a multi-agent system-based virtual personal assistant is an attempt towards improving health care service delivery. We have developed a Multi Agent System and user interface for management of diabetes patients where the patients and medical specialist can interact easily without necessarily visiting the clinic. The application will enable the users to have regular interactions with each other, reduce the cost of going to the clinic, saves patients and medical personnel time. In order to design the application and user interface, we adopted a user centered approach and conducted interviews with the potential users. We also reviewed existing materials for data. Qualitative and quantitative data were collected during the development process. The application and user interface were evaluated by the potential users (patients and medical personnel). The user evaluation of the system shows that the participants were pleased with the application and the user interface. They interacted with the user interface with ease and they encountered little or no difficulty. Keywords: multi-agent, e-health, virtual personal assistant, information and communication technology
A novel 5′‐flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic‐onset juvenile idiopathic arthritis (2001)

This is the first report of a SNP in the MIF gene. This polymorphism is associated with systemic-onset JIA.
Protection against cisplatin-induced nephrotoxicity by a carbon monoxide-releasing molecule (2005)

Nephrotoxicity is one of the main side effects caused by cisplatin (CP), a widely used antineoplastic agent. Here, we examined the effect of a novel water-soluble carbon monoxide-releasing molecule (CORM-3) on CP-mediated cytotoxicity in renal epithelial cells and explored the potential therapeutic benefits of carbon monoxide in CP-induced nephrotoxicity in vivo. Exposure of LLC-PK(1) cells to CP (50 microM) caused significant apoptosis as evidenced by caspase-3 activation and an increased number of floating cells. Treatment with CORM-3 (1-50 microM) resulted in a remarkable and concentration-dependent decrease in CP-induced caspase-3 activity and cell detachment. This effect involved activation of the cGMP pathway as 1H-oxadiazole [4, 3-a] quinoxaline-1-ore (ODQ), a guanylate cyclase inhibitor, completely abolished the protection elicited by CORM-3. Using a rat model of CP-induced renal failure, we found that treatment with CP (7.5 mg/kg) caused a significant elevation in plasma urea (6.6-fold) and creatinine (3.1-fold) levels, which was accompanied by severe morphological changes and marked apoptosis in tubules at the corticomedullary junction. A daily administration of CORM-3 (10 mg/kg ip), starting 1 day before CP treatment and continuing for 3 days thereafter, resulted in amelioration of renal function as shown by reduction of urea and creatinine levels to basal values, a decreased number of apoptotic tubular cells, and an improved histological profile. A negative control (iCORM-3) that is incapable of liberating CO failed to prevent renal dysfunction mediated by CP, indicating that CO is directly involved in renoprotection. Our data demonstrate that CORM-3 can be used as an effective therapeutic adjuvant in the treatment of CP-induced nephrotoxicity.
Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes (1997)

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their confounding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. Fourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P < .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared with 5 of 11 (45.5%, P < .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC followed-up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo prognostic model over-predicted survival. Whereas it is a relatively rare complication of cirrhotic PBC in women, HCC is a relatively common cause of death in male PBC patients with cirrhosis. HCC typically develops several years after the onset of cirrhosis, and is poorly predicted by prognostic models. In view of these findings, consideration should be given to careful screening for HCC in male PBC patients with cirrhosis. The risk of HCC development may be an additional reason to consider earlier transplantation in these patients.
The Design and Performance of a Shared Disk File System for IRIX (1998)

: In this paper we present a new storage architecture for clusters that creates a shared memory of disk storage that is uniformly accessible to all cluster clients, scales to large capacity, and provides very high performance and connectivity. The cluster structure resembles a symmetric multiprocessor (SMP) in that clients (processors) can access disk data (memory) across a local area network like Fibre Channel (a bus or other interconnection network). All clients can see and access the same disk data with perfect consistency. Our approach avoids buffer copy overheads and server bottlenecks found in traditional file systems while scaling to potentially large numbers of clients and large capacity disk systems. We provide a description of the basic file system design, our current implementation on SGI IRIX operating system, and detailed benchmarking and performance analysis results. Good speedup and throughput is achieved for large files across 3 clients and 4 high performance disk arra...
Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence (1991)

The role of bacterial adherence in the persistence of bacteria in the human urinary tract was analyzed. Women with chronic symptomatic urinary tract infections were subjected to deliberate colonization with nonvirulent Escherichia coli, after eradication of their current infections. E. coli organisms were instilled into the bladder through a catheter. The strain used for colonization, E. coli 83972, was isolated from a patient with stable bacteriuria. It lacked expressed adherence factors and did not belong to the uropathogenic O:K:H serotypes. Strain 83972 was transformed with the pap and pil DNA sequences encoding Gal alpha 1-4Gal beta- and mannose-specific (type 1) adhesins. Patients were colonized with a mixture of the wild-type and the transformed strains. E. coli 83972 caused stable bacteriuria for greater than 30 days in 7 of 12 individuals. In contrast, the Gal alpha 1-4 Gal beta-recognizing or mannose-binding transformants were eliminated within 48 h. The consistent superiority of the wild-type strain in establishing stable bacteriuria when compared with the adhesive transformants did not appear to be due to differences in growth rates or to plasmid segregation. Rather, the transformants expressing the adhesin determinants were selectively eliminated by the host. This suggested that the acquisition of adherence factors is not sufficient to increase the fitness of E. coli for survival in the urinary tract of humans.
Thermodynamics of Radiative Emission Processes (1960)

A basic assumption implicit in the application of thermodynamics to the electromagnetic field is that the laws of thermodynamics are locally valid for radiative emission and absorption processes. This means that a certain minimum amount of entropy must be created by the radiative process itself. It is shown, by considering the extreme case in which the spontaneous emission of a natural spectral line is the only process taking place, that this assumption is correct, and that its validity is essentially a consequence of the uncertainty principle as expressed by the reciprocal relationship between natural line breadth and lifetime.
Predicting Visual Function from the Measurements of Retinal Nerve Fiber Layer Structure (2010)

The BRBF generates clinically useful relationships that relate topographical maps of RNFL measurement to VF locations and allows the VF sensitivity to be predicted from structural measurements. This method may allow clinicians to evaluate structural and functional measures in the same domain. It could also be generalized to use other structural measures.
Sex Steroids Modify Working Memory (2000)

In the last ten years, numerous mechanisms by which sex steroids modify cortical function have been described. For example, estrogen replacement improves verbal memory in women, and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function. Little is known about sex steroid effects on other aspects of memory, such as frontal lobe-mediated working memory. We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women. Before hormone supplementation, working memory, tested with the Subject Ordered Pointing Test (SOP), was worse in older subjects than younger subjects, and there was no evidence of gender differences at either age. Testosterone supplementation improved working memory in older men, but a similar enhancement of working memory was not found in older women supplemented with estrogen. In men, testosterone and estrogen effects were reciprocal - with better working memory related to a higher testosterone to estrogen ratio. These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life.
Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis (2016)

CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration.
Production of cellulolytic and xylanolytic enzymes during growth of the anaerobic fungus Piromyces sp. on different substrates (1992)

Piromyces sp. strain E2, an anaerobic fungus isolated from an Indian elephant (hindgut fermenter) was tested for its ability to ferment a range of substrates. The fungus was able to use bagasse, cellobiose, cellulose, fructose, glucose, lactose, mannose, starch, wheat bran, wheat straw, xylan and xylose. Formate and acetate were the main fermentation products after growth on these substrates. The amount of carbon found in the fermentation products of cultures, in which substrate digestion was complete averaged 88.5 mM, or 59% of the carbon offered as substrate. No growth was observed on other substrates tested. Lactose, starch, cellobiose and filter paper cellulose were good inducers of cellulolytic and xylanolytic enzymes. Cellulolytic and xylanolytic enzymes were produced constitutively by Piromyces strain E2, although enzyme activities were generally lower after growth on glucose and other soluble sugars. Complex substrates (bagasse, wheat bran, and wheat straw) were good inducers for xylanolytic enzymes but not for cellulolytic enzymes. The extracellular protein banding pattern after SDS-PAGE was therefore only slightly affected by the growth substrate. Identical beta-glucosidase and endoglucanase activity patterns were found after growth on different substrates. This indicated that differences in enzyme activities were not the result of secretion of different sets of isoenzymes although it remains possible that the relative amount of each isoenzyme produced is influenced by the growth substrate.
Therapeutic Uses of Inorganic Nitrite and Nitrate (2008)

Potential carcinogenic effects, blue baby syndrome, and occasional intoxications caused by nitrite, as well as the suspected health risks related to fertilizer overuse, contributed to the negative image that inorganic nitrite and nitrate have had for decades. Recent experimental studies related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, however, paint a different picture and have led to a renewed interest in the physiological and pharmacological properties of nitrite and nitrate. The range of effects reported suggests that these simple oxyanions of nitrogen have a much richer profile of biological actions than hitherto assumed, and several efforts are currently underway to investigate possible beneficial effects in the clinical arena. We provide here a brief historical account of the medical uses of nitrite and nitrate over the centuries that may serve as a basis for a careful reassessment of the health implications of their exposure and intake and may inform investigations into their therapeutic potential in the future.
ChemInform Abstract: TETRAISOPROPYLDISILOXANE‐1,3‐DIYL, A GROUP FOR SIMULTANEOUS PROTECTION OF 3′‐ AND 5′‐HYDROXY FUNCTIONS OF NUCLEOSIDES (1979)

Abstract Das Dichlortetraisopropyldisiloxan (II) reagiert mit Uridin (Ia) oder anderen Nucleosiden (Ib) zu den in 3′‐ und 5′‐Positionen geschützten Produkten (III).
Surface Plasmon Resonance Study of G Protein/Receptor Coupling in a Lipid Bilayer-Free System (2006)

Surface plasmon resonance (SPR) spectroscopy is a technique to study protein-protein interactions in real time; however, application of SPR spectroscopy for investigations of membrane receptors is difficult with respect to functional and uniform immobilization of receptors on a biosensor surface. In the current study, we developed a simple, direct, biosensor-based approach to monitor the molecular interactions between G protein transducin (Gt) and rhodopsin (Rho), a prototypical G protein-coupled receptor (GPCR). Detergent-solubilized dark-adapted Rho was captured onto a biosensor surface via lectin interaction, enabling site-directed immobilization of the receptor that made its cytoplasmic surface accessible to a coupling G protein. The system resembled the natural system with respect to receptor density, binding of Gt following flash or constant light application, fast GTP-dependent dissociation of Gt from Rho, regeneration of Rho, and dependence of Gt binding on light intensity and on concentration of Gt. The apparent KD of the Gt/Rho interaction was 13.6 nM. Our results validate the use of SPR spectroscopy as a tool to study G protein activation in GPCR systems and could be extended for application to other interaction partners of GPCRs.
Drugs in Clinical Development for Chronic Obstructive Pulmonary Disease (2005)

Many drugs may be potentially useful in the treatment of chronic obstructive pulmonary disease (COPD), but relatively few become available for human use due to lack of safety, lack of efficacy, or both. This is an inherent risk in the drug development process, which coupled with the limited understanding of the molecular pathogenesis of COPD, has produced a trend toward improving existing compounds rather than to develop new compounds. This review focuses on improved existing compounds and newly discovered compounds that are in clinical trials, but not yet marketed. The improved existing compounds include: isomers of the long-acting bronchodilators, once-daily beta2-adrenoceptor agonists, anticholinergics and corticosteroids. The pool of novel compounds is in constant fluctuation and comprises anti-inflammatory drugs, antioxidants, leukotriene modifiers and a number of compounds aimed at treating different aspects of COPD such as pulmonary hypertension and hypophosphatemia.
Interaction of synthetic analogs of distamycin with poly(dA-dT): role of the conjugated N-methylpyrrole system (1987)

Two synthetic analogues of distamycin (Dst), PPA and PAP, containing a saturated beta-alanine moiety substituting for an N-methylpyrrole chromophore were studied for their interactions with the double-stranded alternating copolymer poly(dA-dT).poly(dA-dt) [abbreviated as poly(dA-dT)], with UV absorption and circular dichroism (CD) spectroscopy. The distinctive feature of these analogues is the difference in the extents of extended conjugation due to contiguous pyrrole rings: it decreases in the order Dst greater than PPA greater than PAP. Both these analogues bind to poly(dA-dT) in a way similar to Dst, as suggested from the observed red shift in the UV spectra of the ligands upon complexation and the appearance of induced Cotton effects (in the 290-350-nm region) in the CD spectra of the complexes. A comparative study of (i) the spectral features of the complexes between these ligands, Dst and netrospin (Nt) and poly(dA-dT), and (ii) the binding parameters for the association with the polynucleotide suggests that the number and relative positions of the pyrrole moieties influence the spectral features and thermodynamic stabilities of the complexes, and the latter show a progressive decrease in the order Dst greater than Nt greater than PPA greater than PAP. Implications of these results vis-à-vis the molecular basis of Dst-DNA interaction are discussed.
Comparative assessment of human and farm animal faecal microbiota using real-time quantitative PCR (2009)

Pollution of the environment by human and animal faecal pollution affects the safety of shellfish, drinking water and recreational beaches. To pinpoint the origin of contaminations, it is essential to define the differences between human microbiota and that of farm animals. A strategy based on real-time quantitative PCR (qPCR) assays was therefore developed and applied to compare the composition of intestinal microbiota of these two groups. Primers were designed to quantify the 16S rRNA gene from dominant and subdominant bacterial groups. TaqMan probes were defined for the qPCR technique used for dominant microbiota. Human faecal microbiota was compared with that of farm animals using faecal samples collected from rabbits, goats, horses, pigs, sheep and cows. Three dominant bacterial groups (Bacteroides/Prevotella, Clostridium coccoides and Bifidobacterium) of the human microbiota showed differential population levels in animal species. The Clostridium leptum group showed the lowest differences among human and farm animal species. Human subdominant bacterial groups were highly variable in animal species. Partial least squares regression indicated that the human microbiota could be distinguished from all farm animals studied. This culture-independent comparative assessment of the faecal microbiota between humans and farm animals will prove useful in identifying biomarkers of human and animal faecal contaminations that can be applied to microbial source tracking methods.
Evolutionary variation of the CCAAT-binding transcription factor NF-Y (1992)

NF-Y is a CCAAT-specific transcription factor thought to be involved in the regulation of a variety of eukaryotic genes. It shows a striking sequence similarity with the yeast factor HAP2/3. In an attempt to trace back its evolutionary history, we succeeded in isolating NF-Y cDNA clones from a plant and from several species of vertebrates. The patterns of sequence conservation delineate potential functional domains: A central, highly conserved, domain likely responsible for DNA-binding and subunit interaction; more evolutionarily flexible flanking regions, in which variability is clustered, individualizing conserved glutamine or acidic amino-acids putatively involved in protein-protein contacts.