gebhart/patrepeval huggingface dataset:
Weekly Pulse Methotrexate in Rheumatoid Arthritis (1985)

Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p less than or equal to 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit.
Synthesis, Characterization, and Reactivity of Arylpalladium Cyanoalkyl Complexes:  Selection of Catalysts for the α-Arylation of Nitriles (2002)

A new coupling process, the palladium-catalyzed alpha-arylation of nitriles, was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. Complexes of 1,2-bis(diphenylphosphino)benzene (DPPBz), 1,1'-bis(di-i-propylphosphino)ferrocene (D(i)()PrPF), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), and diphenylethylphosphine (PPh(2)Et) were prepared. Coordination to palladium through the alpha-carbon was observed for DPPBz-ligated complexes and for complexes of primary and benzylic nitrile anions. However, the anion of isobutyronitrile was coordinated to palladium through the cyano-nitrogen when the complex was ligated by D(i)()PrPF. The isobutyronitrile anion displaced a phosphine ligand to form a C,N-bridged dimer when generated from PPh(2)Et-ligated palladium. These results suggest that the nitrile anion preferentially coordinates to palladium through the carbon atom in the absence of steric effects. Thermolysis of the arylpalladium cyanoalkyl complexes led to reductive elimination that formed alpha-aryl nitriles. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form alpha-aryl nitriles in good yields are reported.
Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects (2011)

Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure-activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H(1) receptors may significantly advance schizophrenia therapy.
An Automatic Electronic Contract Document Signing System in a Secure Environment (2006)

Superimposing electronic signing data on a signed electronic contract usually involves a large number of complex manual steps. These manual steps are tedious and may cause security faults. In this paper, we present an automatic electronic contract document signing system in a secure environment. The system comprises a document and signature profile module, a signing text template module and a signing information superimposed module. The document and signature profile module parses the contract document and signature information. Based on this information, the signing text template module creates a signing text template with empty text fields. The signing information superimposed module carry out a novel electronic document signing method. This novel method consists of four processing steps: inserting signing text data into empty text fields, converting the text template into an image template, adding signing image data onto the image template, and superimposing the signing image template on the contract document to produce a signed electronic contract document. This automation system has found to improve substantially the efficiency, and at the same time eliminate the potential for human errors and security breaches in signing electronic contract documents.
Activation of the trans geometry in platinum antitumor complexes. Synthesis, characterization, and biological activity of complexes with the planar ligands pyridine, N-methylimidazole, thiazole, and quinoline. Crystal and molecular structure of trans-dichlorobis(thiazole)platinum(II) (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActivation of the trans geometry in platinum antitumor complexes. Synthesis, characterization, and biological activity of complexes with the planar ligands pyridine, N-methylimidazole, thiazole, and quinoline. Crystal and molecular structure of trans-dichlorobis(thiazole)platinum(II)Marijo Van Beusichem and Nicholas FarrellCite this: Inorg. Chem. 1992, 31, 4, 634–639Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://doi.org/10.1021/ic00030a021RIGHTS & PERMISSIONSArticle Views1275Altmetric-Citations192LEARN 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 InReddit PDF (784 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
On-chip coherent combining of angled-grating diode lasers toward bar-scale single-mode lasers (2012)

Single mode operation of broad-area diode lasers, which is the key to obtain high power, high brightness sources, is difficult due to highly nonlinear materials and strong coupling between gain and index. Conventional broad-area lasers usually operate with multiple modes and have poor beam quality. Laser bars usually consist of incoherently combined broad-area single emitters placed side by side. In this article, we have demonstrated a novel integrated laser architecture in which Bragg diffraction is used to realize simultaneous modal control and coherent combining of broad-area diode lasers. Our experimental results show that two 100 μm wide, 1.3mm long InP broad-area lasers provide near-diffraction-limited output beam and are coherently combined at the same time without any external optical components. Furthermore, our design can be expanded to a coherently combined broad-area laser array that turns a laser bar into a coherent single mode laser with diffraction-limited beam quality.
Pharmacokinetics, Safety, and Tolerability of R411, a Dual α4β1‐α4β7 Integrin Antagonist After Oral Administration at Single and Multiple Once‐Daily Ascending Doses in Healthy Volunteers (2004)

R411 is a dual alpha4beta1-alpha4beta7 integrin antagonist under development for the treatment of chronic asthma. The objective of this study was to investigate the pharmacokinetics and safety of R411 and its active metabolite, RO0270608, in humans. A 3-part phase I trial was conducted in 132 healthy volunteers: (1) 12 subjects received 200 mg R411 as a single oral dose or 100 mg RO0270608 as an intravenous infusion in a 1-sequence crossover design; (2) 7 groups of 10 subjects received 1 of 7 single oral doses of R411 (10-1200 mg) in a parallel, placebo-controlled, ascending adaptive dose design; and (3) 5 groups of 10 subjects each received repeated oral qd doses of R411 (50-900 mg) for up to 3 weeks in a parallel, placebo-controlled, ascending adaptive dose design. The absolute bioavailability of RO0270608 (mean +/- standard deviation) after oral administration of R411 was 27% +/- 4%, and the terminal half-life was 7.33 +/- 2.29 hours. After IV infusion of RO0270608, total clearance (mean +/- standard deviation) was 19.4 +/- 7.1 L/h, and the volume of distribution was 93.1 +/- 36.1 L. After single ascending oral doses of R411, area under the concentration-time curve from 0 to infinity of active metabolite RO0270608 increased proportionally from 150 to 1200 mg (P > .05). Following repeated administration, the oral clearance was independent of time. No drug accumulation was observed, and no safety concerns were revealed up to a dose of 900 mg after up to 3 weeks of treatment.
How does glomerular epithelial cell injury contribute to progressive glomerular damage? (1994)

Glomerular visceral epithelial cells, unlike epithelial cells in other organs or in the more distal segments of the nephron, are highly differentiated, terminal cells that do not undergo cell division under physiological conditions in the postnatal period or during conditions that result in renal hypertrophy. Adjacent cells are connected to each other at the level of complex interdigitations or foot processes by filtration slit diaphragms. This particular arrangement contributes to the extremely high hydraulic conductivity of the normal glomerular capillary. Toxic and metabolic damage to the visceral epithelial cells or conditions of extreme glomerular hypertrophy result, in the short term, in diffuse or focal simplification and flattening of the foot processes. The areas of the capillary wall covered by such a simplified epithelium are likely to have a greatly reduced hydraulic conductivity which results from the greatly diminished surface area available for filtration. The rearrangement of foot processes also leads to focal areas of denudation of the basement membrane. Such denuded areas, however, are likely to result in an increase in local hydraulic flux, especially under conditions of capillary hypertension. Such defects have been shown to be the pathway of increased permeability to macromolecular markers and proteinuria. Large plasma proteins are retained in the subendothelium by the size-restrictive water-filled channels of the lamina densa and accumulate upstream in the form of hyaline which eventually occludes individual loops. More severe epithelial cell injury and denudation may also result in collapse of entire tuft segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Preparation and studies on immobilized α-glucosidase from baker’s yeast Saccharomyces cerevisiae (2007)

?-Glucosidase from S. cerevisiae was covalently immobilized onto Sepabeads EC-EA by the glutaraldehyde method. An analysis of the variables controlling the immobilization process is first presented and it is shown that the highest coupling of ?-glucosidase occurred within 24 h. Also, a loading of 30 mg/g support proved to be effective, resulting in a rather high activity of around 45 U g-1 with a satisfactory degree of enzyme fixed. Both free and immobilized enzymes were then characterized by determining the activity profile as a function of pH, temperature and thermal stability. The obtained immobilized preparation showed the same optimum pH, but a higher optimum temperature compared with the soluble one. In addition, the immobilized enzyme treated at 45 ?C for 1 h still retained an activity of around 20 %, whereas the free enzyme completely lost its original activity under this condition. In conclusion, the developed immobilization procedure is quite simple, easily reproducible and provides a promising solution for the application of immobilized ?-glucosidase.
Preserving privacy in a network of mobile computers (2002)

Even as wireless networks create the potential for access to information from mobile platforms, they pose a problem for privacy. In order to retrieve messages, users must periodically poll the network. The information that the user must give to the network could potentially be used to track that user. However, the movements of the user can also be used to hide the user's location if the protocols for sending and retrieving messages are carefully designed. We have developed a replicated memory service which allows users to read from memory without revealing which memory locations they are reading. Unlike previous protocols, our protocol is efficient in its use of computation and bandwidth. We show how this protocol can be used in conjunction with existing privacy preserving protocols to allow a user of a mobile computer to maintain privacy despite active attacks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Apolipoprotein CIII promotes Ca <sup>2+</sup> -dependent β cell death in type 1 diabetes (2004)

In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic beta cell. Although the exact molecular mechanisms underlying beta cell destruction are not known, sera from T1D patients have been shown to promote Ca(2+)-induced apoptosis. We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free intracellular Ca(2+) concentration ([Ca(2+)](i)) and beta cell death. The apoCIII-induced increase in [Ca(2+)](i) reflects an activation of the voltage-gated L-type Ca(2+) channel. Both the effects of T1D sera and apoCIII on the beta cell are abolished in the presence of antibody against apoCIII. Increased serum levels of apoCIII can thus account for the increase in beta cell [Ca(2+)](i) and thereby beta cell apoptosis associated with T1D.
Biochemical characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). (1984)

Lysophospholipase from human eosinophils is a protein previously considered based upon antigenic, enzymatic, and electrophoretic similarities to be the single component of Charcot-Leyden crystals, which are formed in vivo in association with eosinophilic diseases. The identity of eosinophil lysophospholipase and solubilized Charcot-Leyden crystal protein is now established by biochemical criteria, and a basis for the ease of aggregation and crystallization of the protein is identified in its prominent hydrophobicity. Chromatographically purified enzyme and Charcot-Leyden crystal protein formed in vitro functioned as lysophospholipases with identical Michaelis constants (Km approximately equal to 22 microM) for the substrate lysopalmitoylphosphatidylcholine and had blocked amino-terminal residues and almost identical amino acid compositions. The propensity of lysophospholipase to aggregate was not due to extensive intermolecular disulfide bonding because it contained a single cysteine residue as assessed by amino acid analyses and incorporated 0.986 mol of p-chloromercuribenzoic acid/mol of native enzyme or 0.958 mol of iodoacetic acid/mol of reduced and denatured enzyme. By equilibrium dialysis, lysophospholipase bound 3.820 g of detergent/g of protein in 1% sodium dodecyl sulfate and 0.506 g of detergent/g of protein in 10 mM sodium deoxycholate. In addition, monomeric protein demonstrated enhanced binding of detergent as evidenced by its aberrantly rapid electrophoretic mobility in 1%, but not 0.1%, sodium dodecyl sulfate. The hydrophobic nature of this protein, which accounts for 10% of the protein of the eosinophil, may contribute to its unique propensity for crystallization in vivo.
Syntheses and reactions of 3-phenyloxete and the parent unsubstituted oxete (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSyntheses and reactions of 3-phenyloxete and the parent unsubstituted oxeteLouis E. Friedrich and Patrick Yuk-Sun LamCite this: J. Org. Chem. 1981, 46, 2, 306–311Publication Date (Print):January 1, 1981Publication History Published online1 May 2002Published inissue 1 January 1981https://pubs.acs.org/doi/10.1021/jo00315a016https://doi.org/10.1021/jo00315a016research-articleACS PublicationsRequest reuse permissionsArticle Views1604Altmetric-Citations34LEARN 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
Real-Time Laser Spark Spectroscopy of Particulates in Combustion Environments (1989)

Several laser-based techniques are being developed to provide in situ determinations of size, velocity, and elemental composition for individual particulates in combustion environments. Emphasis is placed on composition measurements using laser spark spectroscopy, and data for particulates entrained in gaseous flows are presented. Size and velocity of individual particles are determined by a colinear two-color laser scattering technique. Laser sparks (high-temperature plasmas) are produced from single particles with the use of a Q-switched Nd:YAG laser, and time-resolved emission spectra are observed. Results indicate a high sensitivity of the technique to mineral matter in coal particles. The detection of numerous constituent species is demonstrated, and trends observed in elemental distribution are in agreement with x-ray fluorescence measurements. Initial semi-quantitative results are compared with standard chemical analyses of the bulk material.
Control of reflectivity and bistability in displays using cholesteric liquid crystals (1994)

It is demonstrated that the reflective properties and bistability of cholesteric liquid crystals can be controlled by proper surface treatment and dispersed polymers. Dispersing a polymer in the liquid crystal or using a cell with an inhomogeneous surface anchoring creates permanent defects which result in long-term bistability, high contrast at large viewing angles, and gray scale. The wide-angle, reflective feature makes cholesteric materials suitable for displays without backlights and bistability provides flicker-free operation.
Mapping <i>PrBn</i> and Other Quantitative Trait Loci Responsible for the Control of Homeologous Chromosome Pairing in Oilseed Rape (<i>Brassica napus</i> L.) Haploids (2006)

In allopolyploid species, fair meiosis could be challenged by homeologous chromosome pairing and is usually achieved by the action of homeologous pairing suppressor genes. Oilseed rape (Brassica napus) haploids (AC, n=19) represent an attractive model for studying the mechanisms used by allopolyploids to ensure the diploid-like meiotic pairing pattern. In oilseed rape haploids, homeologous chromosome pairing at metaphase I was found to be genetically based and controlled by a major gene, PrBn, segregating in a background of polygenic variation. In this study, we have mapped PrBn within a 10-cM interval on the C genome linkage group DY15 and shown that PrBn displays incomplete penetrance or variable expressivity. We have identified three to six minor QTL/BTL that have slight additive effects on the amount of pairing at metaphase I but do not interact with PrBn. We have also detected a number of other loci that interact epistatically, notably with PrBn. Our results support the idea that, as in other polyploid species, metaphase I homeologous pairing in oilseed rape haploids is controlled by an integrated system of several genes, which function in a complex manner.
Overexpression of the Cellular DEK Protein Promotes Epithelial Transformation <i>In vitro</i> and <i>In vivo</i> (2009)

High levels of expression of the human DEK gene have been correlated with numerous human malignancies. Intracellular DEK functions have been described in vitro and include DNA supercoiling, DNA replication, RNA splicing, and transcription. We have shown that DEK also suppresses cellular senescence, apoptosis, and differentiation, thus promoting cell growth and survival in monolayer and organotypic epithelial raft models. Such functions are likely to contribute to cancer, but direct evidence to implicate DEK as an oncogene has remained elusive. Here, we show that in line with an early role in tumorigenesis, murine papilloma formation in a classical chemical carcinogenesis model was reduced in DEK knockout mice. Additionally, human papillomavirus E6/E7, hRas, and DEK cooperated in the transformation of keratinocytes in soft agar and xenograft establishment, thus also implicating DEK in tumor promotion at later stages. Finally, adenoviral DEK depletion via short hairpin RNA expression resulted in cell death in human tumor cells in vitro and in vivo, but did not significantly affect differentiated epithelial cells. Taken together, our data uncover oncogenic DEK activities as postulated from its frequent up-regulation in human malignancies, and suggest that the targeted suppression of DEK may become a strategic approach to the treatment of cancer.
Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip (2017)

Using lab-on-chip technology, bulky lab equipment is shrunk into a simple, portable, and quantitative microfluidic chip for DNA diagnostics.