gebhart/patrepeval huggingface dataset:
Structure-activity studies on open-chain analogues of nucleosides: Inhibition of S-adenosyl-L-homocysteine hydrolase and antiviral activity 1. Neutral open-chain analogues (1985)

Over 70 alkyl derivatives of purine bases were examined for their inhibitory effects toward rat liver S-adenosyl-L-homocysteine hydrolase and their antiviral activity. The following structural features must be fulfilled by an inhibitor of SAH-hydrolase: an intact adenine moiety, an alkyl chain bound at the 9-position and bearing a vicinal diol at the 2',3'-position, with 2 S configuration. An additional substitution at the 3-position lowers or annihilates the inhibitory activity. The enzyme inhibition is reversible. Some of the compounds are substrates of adenosine aminohydrolase. All inhibitors of SAH-hydrolase exhibit antiviral activity, e.g. against vesicular stomatitis virus and vaccinia virus in cell culture, and this antiviral correlates with the inhibition of SAH-hydrolase.
Efficacy and safety of ustekinumab in Japanese patients with moderate‐to‐severe plaque‐type psoriasis: Long‐term results from a phase 2/3 clinical trial (2011)

This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.
Experimental grain dust atmospheres generated by wet and dry aerosolization techniques (1994)

Properties of grain dust aerosols generated using wet and dry techniques were studied. Relative to the dry aerosol generation, the wet generation technique yielded a smaller particle size distribution (MMAED of 1.5 microns vs. 15.5 microns) but also reduced the viability of microorganisms. Analysis of dust mass and endotoxin activity on cascade impactor stages demonstrated equivalent partitioning of the airborne endotoxin with the dust mass for aerosols produced by either generation method. Comparison of laboratory-generated atmospheres to field sampling indicated a greater proportion of respirable microorganisms in soybean handling facilities than were generated using the dry aerosol system. Limitations of both aerosol generation systems were found that may affect the validity of inhalation toxicology studies in which these bioaerosols are artificially created.
Stereochemistry of lysine 2,3-aminomutase (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemistry of lysine 2,3-aminomutaseD. John Aberhart, Horng Jau Lin, and Bruce H. WeillerCite this: J. Am. Chem. Soc. 1981, 103, 22, 6750–6752Publication Date (Print):November 1, 1981Publication History Published online1 May 2002Published inissue 1 November 1981https://pubs.acs.org/doi/10.1021/ja00412a040https://doi.org/10.1021/ja00412a040research-articleACS PublicationsRequest reuse permissionsArticle Views217Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Tissue Factor Produced by the Endocrine Cells of the Islets of Langerhans Is Associated With a Negative Outcome of Clinical Islet Transplantation (2005)

There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.
Oral tolerization with peptide 336–351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease (2004)

Behcet's disease (BD) specific peptide (p336-351) was identified within the human 60 kD heat shock protein (HSP60). Oral p336-351 induced uveitis in rats which was prevented by oral tolerization with the peptide linked to recombinant cholera toxin B subunit (CTB). This strategy was adopted in a phase I/II clinical trial by oral administration of p336-351-CTB, 3 times weekly, followed by gradual withdrawal of all immunosuppressive drugs used to control the disease in 8 patients with BD. The patients were monitored by clinical and ophthalmological examination, as well as extensive immunological investigations. Oral administration of p336-351-CTB had no adverse effect and withdrawal of the immunosuppressive drugs showed no relapse of uveitis in 5 of 8 patients or 5 of 6 selected patients who were free of disease activity prior to initiating the tolerization regimen. After tolerization was discontinued, 3 of 5 patients remained free of relapsing uveitis for 10-18 months after cessation of all treatment. Control of uveitis and extra-ocular manifestations of BD was associated with a lack of peptide-specific CD4+ T cell proliferation, a decrease in expression of TH1 type cells (CCR5, CXCR3), IFN-gamma and TNF-alpha production, CCR7+ T cells and costimulatory molecules (CD40 and CD28), as compared with an increase in these parameters in patients in whom uveitis had relapsed. The efficacy of oral peptide-CTB tolerization will need to be confirmed in a phase III trial, but this novel strategy in humans might be applicable generally to autoimmune diseases in which specific antigens have been identified.
Drug Targeting into the Central Nervous System by Stereotactic Implantation of Biodegradable Microspheres (1994)

Controlled drug release in the central nervous system through an implantable polymeric vector has been developed in recent years. For this purpose, different polymeric devices composed primarily of synthetic biocompatible and biodegradable polymers have been investigated. The first polymeric devices developed were macroscopic implants (monolithic devices), which required open surgery for implantation. Microencapsulation methods, however, allow the production of microparticles or nanoparticles loaded with neuroactive drugs. Because of their size, these micro- or nanoparticles may be easily implanted by stereotaxy in discrete, precise, and functional areas of the brain without causing damage to the surrounding tissue. Presently, this method is most frequently applied in the fields of neuro-oncology and neurodegenerative diseases, but neurologically, the potential applications of drug targeting by stereotactic implantation of drug-loaded particles are legion.
Partial volume tissue classification of multichannel magnetic resonance images-a mixel model (1991)

A single volume element (voxel) in a medical image may be composed of a mixture of multiple tissue types. The authors call voxels which contain multiple tissue classes mixels. A statistical mixel image model based on Markov random field (MRF) theory and an algorithm for the classification of mixels are presented. The authors concentrate on the classification of multichannel magnetic resonance (MR) images of the brain although the algorithm has other applications. The authors also present a method for compensating for the gray-level variation of MR images between different slices, which is primarily caused by the inhomogeneity of the RF field produced by the imaging coil.
BNP in decompensated heart failure: diagnostic, prognostic and therapeutic potential. (2001)

B-type or brain natriuretic peptide (BNP) is a balanced vasodilator with no inotropic nor chronotropic properties. Plasma levels can be used in diagnosis and prognosis of patients with heart failure, hypertension, myocardial infarction, right ventricular dysfunction and cor pulmonale. Intravenous therapy with BNP (nesiritide) in nearly 1000 patients demonstrated significant dose-dependent reductions in pulmonary capillary wedge pressure and systemic vascular resistance, as well as increased cardiac index. Compared to dobutamine, it is not pro-arrhythmic and has no effect on heart rate. Compared to standard therapy, it improves dyspnea by 3 h of therapy and leads to fewer headaches and arrhythmias than the commonly used intravenous agents nitroglycerin and dobutamine, respectively. Current research suggests an important role for use of nesiritide in the treatment of decompensated heart failure.
Introduction and Overview (2006)

Gender pay discrimination has been outlawed in all member states of the European Union (EU) for many years. Article 119 of the Treaty of Rome, establishing the European Communities in 1957, already introduced the principle that women and men should receive equal pay for equal work. Since 1975, this basic principle has been refined and extended through a number of European Directives. The latter extend the principle of equal pay to work of equal value, guarantee the right to equal treatment in the workplace (that is, access to employment, vocational training, promotion and working conditions), and provide for equal treatment of women and men with respect to both statutory social security and occupational social security (Rice, 1999). Another important development towards the reduction of gender pay inequalities was the adoption in December 1997 of a European Directive on the burden of proof in cases of discrimination based on sex. This Directive implies that: when persons consider themselves wronged because the principle of equal treatment has not been applied to them establish, before a court or other competent authority, facts from which it may be presumed that there has been direct or indirect discrimination, it shall be for the respondent to prove that there has been no breach of the principle of equal treatment. (Official Journal of the European Communities, 1998, p. 8) KeywordsEuropean UnionEuropean Union CountryWage InequalityWage GrowthEuropean Community Household PanelThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate (2015)

Progressive multifocal leukoencephalopathy can occur in patients with lymphocyte counts between 450 and 700/μl, produce only faint symptoms and is not excluded by negative JC-virus-polymerase chain reaction in cerebrospinal fluid. The incidence of progressive multifocal leukoencephalopathy may thus be underestimated and a more careful surveillance of patients would be necessary.
Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria (1993)

Extracellular solute-binding proteins of bacteria serve as chemoreceptors, recognition constituents of transport systems, and initiators of signal transduction pathways. Over 50 sequenced periplasmic solute-binding proteins of gram-negative bacteria and homologous extracytoplasmic lipoproteins of gram-positive bacteria have been analyzed for sequence similarities, and their degrees of relatedness have been determined. Some of these proteins are homologous to cytoplasmic transcriptional regulatory proteins of bacteria; however, with the sole exception of the vitamin B12-binding protein of Escherichia coli, which is homologous to human glutathione peroxidase, they are not demonstrably homologous to any of the several thousand sequenced eukaryotic proteins. Most of these proteins fall into eight distinct clusters as follows. Cluster 1 solute-binding proteins are specific for malto-oligosaccharides, multiple oligosaccharides, glycerol 3-phosphate, and iron. Cluster 2 proteins are specific for galactose, ribose, arabinose, and multiple monosaccharides, and they are homologous to a number of transcriptional regulatory proteins including the lactose, galactose, and fructose repressors of E. coli. Cluster 3 proteins are specific for histidine, lysine-arginine-ornithine, glutamine, octopine, nopaline, and basic amino acids. Cluster 4 proteins are specific for leucine and leucine-isoleucine-valine, and they are homologous to the aliphatic amidase transcriptional repressor, AmiC, of Pseudomonas aeruginosa. Cluster 5 proteins are specific for dipeptides and oligopeptides as well as nickel. Cluster 6 proteins are specific for sulfate, thiosulfate, and possibly phosphate. Cluster 7 proteins are specific for dicarboxylates and tricarboxylates, but these two proteins exhibit insufficient sequence similarity to establish homology. Finally, cluster 8 proteins are specific for iron complexes and possibly vitamin B12. Members of each cluster of binding proteins exhibit greater sequence conservation in their N-terminal domains than in their C-terminal domains. Signature sequences for these eight protein families are presented. The results reveal that binding proteins specific for the same solute from different bacteria are generally more closely related to each other than are binding proteins specific for different solutes from the same organism, although exceptions exist. They also suggest that a requirement for high-affinity solute binding imposes severe structural constraints on a protein. The occurrence of two distinct classes of bacterial cytoplasmic repressor proteins which are homologous to two different clusters of periplasmic binding proteins suggests that the gene-splicing events which allowed functional conversion of these proteins with retention of domain structure have occurred repeatedly during evolutionary history.(ABSTRACT TRUNCATED AT 400 WORDS)
Inactivation of the ribonucleic acid-processing enzyme ribonuclease E blocks cell division (1981)

The Escherichia coli endoribonuclease ribonuclease E, the enzyme responsible for the processing of precursor 5S ribosomal ribonucleic acid (RNA) from the nascent ribosomal RNA transcript, is thermolabile in rne-3071 mutants. When cells of such a strain were shifted to a nonpermissive temperature, the function of ribonuclease E was almost instantaneously inactivated. However, a threefold linear increase in absorbance took place over a 3-h period, and similar linear increases occurred in all the macromolecules we measured, including deoxyribonucleic acid, RNA, protein, and lipopolysaccharides. Interestingly, during this period, the cells elongated but failed to divide. Thus, these experiments suggest that an early effect of inactivation of the RNA processing enzyme ribonuclease E is a block in cell division.
Different mechanisms of Campath-1H-mediated depletion for CD4+and CD8+T cells in peripheral blood (2006)

It is assumed that complement and noncomplement-mediated mechanisms are similarly responsible for Campath-1H-mediated killing of all T-cell subtypes in vivo. However, the differing surface expression of CD52 on T-cell subtypes suggests that may not be the case. The purpose of this study is to determine the extent and mechanism of Campath-1H-mediated elimination of different T-cell subtypes in peripheral blood. Whole blood or lymphocytes isolated from peripheral blood of healthy volunteers by Ficoll density centrifugation were incubated with Campath-1H, with or without complement and/or serum, and the resultant T-cell elimination mechanisms studied. For CD4(+) T lymphocytes, 60% and 40% cell death and for CD8(+) T lymphocytes 23% and 77% cell death, in peripheral blood, was mediated by complement and noncomplement mediated mechanisms, respectively. CD4(+) T cells demonstrated approximately twice the amount of surface CD52 compared with CD8(+) T cells, consistent with primarily complement-mediated killing for CD4(+) T cells. Thus, peripheral blood supports differential and partial elimination of T-cell subtypes, suggesting that the complete T-cell elimination seen in transplant recipients is most likely due to contribution from other lymphoid organs.
Fluorescent Molecular Probes II. The Synthesis, Spectral Properties and Use of Fluorescent Solvatochromic Dapoxyl Dyes (1997)

Abstract— 2,5‐Diphenyloxazoles that embody a dimethylamino group at position 4 of the 5‐phenyl ring and a sulfonyl group at position 4 of the 2‐phenyl ring were prepared as new fluorescent solvatochromic dyes. In these molecules, there is a “push‐pull” electron transfer system from the 5‐phenyl moiety to the 2‐phenyl ring. These compounds show strong solvent‐dependent fluorescence that is well correlated with the empirical solvent polarity parameter ET (30). The solvent polarity dependence suggests that the fluorescence arises from an intramolecular charge transfer. The fluorescence‐environment dependence, long emission wavelength, large extinction coefficients, high fluorescence quantum yields and large Stokes shift of the fluorophores can be used to develop ultrasensitive fluorescent molecular probes to study a variety of biological events and processes.
Spot Urine Albumin to Creatinine Ratio and Serum Cystatin C are Effective for Detection of Diabetic Nephropathy in Childhood Diabetic Patients (2012)

Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R(2) = 0.828, P = 0.001) and creatinine clearance (R(2) = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
Pneumococcal cell wall phosphorylcholine elicits polyclonal antibody secretion in mice (1984)

Immunization of mice with phosphorylcholine (PC)-bearing Staphylococcus pneumoniae Type 2, strain 36a (R36a) results in both a PC-specific and a polyclonal increase in splenic plaque-forming cells. The polyclonal increase was observed in all strains tested, including those bearing an X-linked immune defect resulting in an undetectable anti-PC immune response. The magnitude of the polyclonal response is directly related to the amount of bacterial surface PC as detected by enzyme-linked immunosorbent assay. Congenitally athymic (nude) mice mount an anti-PC plaque-forming cell response after R36a immunization but fail to produce a significant polyclonal response. From our results it appears that PC on the cell wall of a bacterium acts both as a polyclonal activator and a specific antigen, stimulating each by different mechanisms.
Adaptive sampling of reflectance fields (2007)

Image-based relighting achieves high quality in rendering, but it requires a large number of measurements of the reflectance field. This article discusses sampling techniques that improve on the trade-offs between measurement effort and reconstruction quality. Specifically, we (i) demonstrate that sampling with point lights and from a sparse set of incoming light directions creates artifacts which can be reduced significantly by employing extended light sources for sampling, (ii) propose a sampling algorithm which incrementally chooses light directions adapted to the properties of the reflectance field being measured, thus capturing significant features faster than fixed-pattern sampling, and (iii) combine reflectance fields from two different light domain resolutions. We present an automated measurement setup for well-defined angular distributions of the incident, indirect illumination. It is based on programmable spotlights with controlled aperture that illuminate the walls around the scene.