gebhart/patrepeval huggingface dataset:
Combination Therapy for Rheumatoid Arthritis (2002)

What can be expected from combination therapy? What is the goal of combination therapy? What criteria allow drug selection? Is combination therapy regularly used for controlling rheumatoid arthritis? What combination therapies have been assessed with clinical trials? What is the contribution of prolonged combination therapy? Conclusion
In Vitro Evaluation of Transdermal Drug Delivery by a Micro-needle Patch (2004)

ABSTRACT SUMMARY: Using micro-needles composed of drug and a soluble GRAS material to form a dissolving matrix, a TheraJect MATTM transdermal drug delivery patch delivered lidocaine with up to 12X more flux than passive delivery in vitro. Drug delivery occurs when the needles dissolve and also through epidermal micro-channels created by micro-needles. There has been rapid progress in molecular biology, to identify and prepare specific peptide, protein and oligonucleotide drugs and vaccines to treat or prevent disease with minimal side
Fundamental limitations on plasma fusion systems not in thermodynamic equilibrium (1997)

Analytical Fokker–Planck calculations are used to accurately determine the minimum power that must be recycled in order to maintain a plasma out of thermodynamic equilibrium despite collisions. For virtually all possible types of fusion reactors in which the major particle species are significantly non-Maxwellian or are at radically different mean energies, this minimum recirculating power is substantially larger than the fusion power. Barring the discovery of methods for recycling the power at exceedingly high efficiencies, grossly nonequilibrium reactors will not be able to produce net power.
Novel total syntheses of (+)-estrone 3-methyl ether, (+)-13.beta.-ethyl-3-methoxygona-1,3,5(10)-trien-17-one, and (+)-equilenin 3-methyl ether (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel total syntheses of (+)-estrone 3-methyl ether, (+)-13.beta.-ethyl-3-methoxygona-1,3,5(10)-trien-17-one, and (+)-equilenin 3-methyl etherNoal Cohen, Bruce L. Banner, Wayne F. Eichel, David R. Parrish, Gabriel Saucy, Jean M. Cassal, Werner Meier, and Andor FuerstCite this: J. Org. Chem. 1975, 40, 6, 681–685Publication Date (Print):March 1, 1975Publication History Published online1 May 2002Published inissue 1 March 1975https://pubs.acs.org/doi/10.1021/jo00894a004https://doi.org/10.1021/jo00894a004research-articleACS PublicationsRequest reuse permissionsArticle Views317Altmetric-Citations55LEARN 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
Assessing Porcine Liver-Derived Biomatrix for Hepatic Tissue Engineering (2004)

Acellular, biologically derived matrices such as small intestinal submucosa have been extensively utilized to induce tissue regeneration and remodeling of connective tissue, vascular grafts, and urinary bladder; however, decellularized scaffolds have not been explored for their potential utility in hepatic tissue engineering. In the case of both extracorporeal hepatocyte-based devices and implantable hepatocyte-scaffold tissue-engineered constructs, maintenance of hepatocellular function is of prime importance. In this study, we specifically explored decellularized, porcine, liver-derived biomatrix (LBM) as a bioresorbable scaffold for primary hepatocytes. Primary rat hepatocytes were cultured on LBM and compared with well-characterized hepatocyte culture models--double-gel cultures that promote maintenance of liver-specific functions for many weeks, and adsorbed collagen monolayers that lead to the rapid decline of hepatocellular function and viability. Hepatocytes were maintained for up to 45 days on LBM and liver-specific functions such as albumin synthesis, urea production, and P-450 IA1 activity were found to be significantly improved over adsorbed collagen cultures. Our data indicate that LBM may be a favorable alternative to existing scaffolds for tissue engineering in that it is bioresorbable, can be easily manipulated, and supports long-term hepatocellular functions in vitro.
Storage of red cell concentrates in CPD-A2 for 42 and 49 days. (1983)

CPD-A2 is a modified CPD blood preservative with adenine, containing 1 1/2 times as much glucose as CPD. Units (450 ml) of blood from 21 normal donors were collected in CPD-A2 in plastic bags and held at room temperature for 8 hr. An 80% red cell concentrate was prepared and this was stored for 42 or 49 days at 4 degrees C, with the containers in either a standing or lying position. Measurements of glucose consumption, red cell ATP, and 2,3-DPG and of plasma hemoglobin, pH, Na+, and K+ were performed on all samples. The size of the "fragile tail" of osmotically fragile red cells was estimated in 12 samples. The poststorage 24 hr viability of their own stored 51Cr-tagged red cells was documented in 19 of the volunteers. At least 4 months after the original donation, a second unit of blood was collected from eight of the donors to make possible intradonor comparison of the biochemical effects of storage position. After 42 days but not after 49 days of storage, red cells in concentrates stored in the lying position had consumed more glucose and had a higher poststorage pH than did cells stored in the standing position. The poststorage 24 hr viability of red cells stored for 42 days averaged 83.6%, with all units exceeding 70% viability. At 49 days the average viability was 69.1%. Although the average viability of cells stored in the lying position for 42 days was higher than that of concentrates stored standing, the difference was not statistically significant at the 5% level. The plasma hemoglobin level showed a weak correlation with viability of stored cells. Red cell ATP levels were correlated with viability only at 42 days' and not at 49 days' storage. Concentrates of red cell collected in CPD-A2 manifested fully satisfactory viability for 42 days. At 49 days storage the results of viability studies were borderline. High plasma hemoglobin values are observed at both 42 and 49 days' storage and may limit the usefulness of red cell concentrates stored for prolonged periods of time.
Treatment of experimental murine candidiasis with liposome-associated amphotericin B (1984)

Mice were challenged intravenously with Candida albicans, and then treated either with nothing (controls), amphotericin B-desoxycholate (AMB), or amphotericin B associated with liposomes (AMB-lipo). AMB-lipo permitted larger doses of amphotericin B to be given, and also appeared to have no severe toxicity in the animal model. High doses of AMB-lipo were protective, but at equal doses, AMB-lipo was not as effective as commercial AMB.
Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii (1992)

Two nucleoside diphosphate analogs, 3'-C-methyl-ADP and 3'-C-methyl-UDP, have been tested as substrate and/or allosteric effectors using the adenosylcobalamin-dependent ribonucleoside diphosphate reductase of Corynebacterium nephridii. Neither analog was a substrate for the reductase. However, they did function as allosteric effectors and as inhibitors of the reduction of ADP and UDP, respectively. The nucleotide analogs did not stimulate the hydrogen exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the cleavage of the 3'-carbon-hydrogen bond is a prerequisite for the exchange reaction. A reinvestigation of the requirements for the exchange reaction revealed that the deoxyribonucleoside diphosphate products are very effective promoters of this reaction. Indeed, the deoxyribonucleoside diphosphates were found to be more effective in promoting the exchange reaction than the ribonucleoside diphosphate substrates. In contrast, the deoxyribonucleoside triphosphate effectors, dATP, dUTP, and dTTP, were only marginally effective as promoters of this reaction.
Heart Rate Reduction Induced by the If Current Inhibitor Ivabradine Improves Diastolic Function and Attenuates Cardiac Tissue Hypoxia (2011)

Long-term HRR induced by ivabradine improves diastolic LV function probably involving attenuated hypoxia, reduced remodeling, and/or preserved nitric oxide bioavailability, resulting from processes triggered early after HRR initiation: angiogenesis and/or preservation of endothelial nitric oxide synthase expression.
Optimization of conduits' shape in micro heat exchangers (1998)

An approximate theory is derived to compute the thermal resistances of flat plate micro heat exchangers whose surfaces are heated with uniform flux. It is demonstrated that the thermal resistance can be minimized by proper selection of uniform conduit geometry. Further reductions in the maximum heated surface temperature and in the heated surface temperature gradients can be achieved by varying the conduit's cross-sectional dimensions as a function of the axial coordinate. This paper illustrates that a conduit's shape can be customized so as to achieve desired objectives.
ChemInform Abstract: Oxidation of Hydrazino‐1,3,5‐triazine. (1990)

Abstract Reaction of the title compound (I) with nitrous acid yields the triazinyl azide (III).
Mutual Gaze Support in Videoconferencing Reviewed (2015)

Videoconferencing allows geographically dispersed parties to communicate by simultaneous audio and video transmissions. It is used in a variety of application scenarios with a wide range of coordination needs and efforts, such as private chat, discussion meetings, and negotiation tasks. In particular, in scenarios requiring certain levels of trust and judgement non-verbal communication, cues are highly important for effective communication. Mutual gaze support plays a central role in those high coordination need scenarios but generally lacks adequate technical support from videoconferencing systems. In this paper, we review technical concepts and implementations for mutual gaze support in videoconferencing, classify them, evaluate them according to a defined set of criteria, and give recommendations for future developments. Our review gives decision makers, researchers, and developers a tool to systematically apply and further develop videoconferencing systems in "serious" settings requiring mutual gaze. This should lead to well-informed decisions regarding the use and development of this technology and to a more widespread exploitation of the benefits of videoconferencing in general. For example, if videoconferencing systems supported high-quality mutual gaze in an easy-to-set-up and easy-to-use way, we could hold more effective and efficient recruitment interviews, court hearings, or contract negotiations.
Production of tPA in recombinant CHO cells under oxygen‐limited conditions (1993)

Animal cell bioreactors are often limited by the oxygen supply. The reduction in oxygen consumption per cell that occurs under hypoxic conditions may be exploited as a method for increasing reactor capacity if additional glucose is provided to offset increased glycolytic activity. The effects of oxygen deprivation on recombinant tPA (tissue-type plasminogen activator) production were investigated using midexponential and slowly growing CHO cells. The specific oxygen consumption rate can be reduced by at least 50% (mild hypoxic conditions) without affecting the cell growth rate, maximum cell concentration, tPA production rate, or tPA quality (as characterized by the tPA-specific activity and SDS-PAGE analysis). This suggests that mild-hypoxic conditions (with sufficient glucose) can be used to double the cell concentration and volumetric tPA production rate (at a constant volumetric oxygen supply rate) without sacrificing product quality. However, anoxic conditions should be avoided. When slowly growing cultures were exposed to anoxia, the tPA production rate decreased by 80% without affecting tPA quality. However, when midexponential cultures were exposed to anoxia, the drop in tPA production was accompanied by a decrease in tPA quality that ranged from a 40% decrease in tPA specific activity to extensive tPA degradation.
Detection of Cocaine Using the Flow Immunosensor (1992)

Abstract A continuous flow immunosensor has been designed for the detection of cocaine in aqueous samples. The continuous flow immunosensor relies on the displacement of fluorophore-labeled antigen from immobilized monoclonal antibody. The sensitivity and accuracy of the flow immunosensor were investigated while varying the parameters of immobilized antibody density, flow rate, amount of antibody-coated Sepharose used in each column, and the saturation of antibody binding sites with fluorophore-labeled antigen. Using a low density of immobilized anti-benzoylecgonine antibody, as little as 5 ng/ml cocaine could be detected. Small amounts of antibody-coated Sepharose could be used repeatedly and the lifetime of the column was proportional to the amount of Sepharose used. Results were obtained in less than a minute and cross-reactivity against various other drugs was negligible.
Synthesis and Characterization of Ni–P-CNT's Nanocomposite Film for MEMS Applications (2005)

An electroless phosphorus nickel-carbon nanotube (Ni-P-CNT) nanocomposite film synthesis and related process for microelectromechanical systems device fabrication have been successfully developed and presented in this paper. With a special acid oxidative method, a well-dispersed nickel-CNT's colloidal solution has been produced without any aggregation, which is very suitable for microstructure fabrication. The nanoindentation measurement indicates that the Young's modulus and hardness of the Ni-P-CNT's nanocomposite film plated in the bath with 0.028-g/L CNTs can greatly increase up to 665.9 and 28.9 GPa, respectively, which are approximately four times larger than that of pure nickel. Moreover, the content of CNTs in the Ni-P-CNT's films is measured by an elemental analyzer. Via the electrical resistivity measurement using a four-point probe, it is found that the electrical property of the nanocomposite film can be well characterized using a Maxwell-Wagner model for a two-phase mixture. The performance improvements of the electrothermal microactuator made of the nanocomposite, including device strength and power efficiency, have been proven similar to the actuator made of the Ni-diamond composites by electrolytic plating by Tsai et al., but with more efficiency and higher strength than the Ni-diamond device does.
Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. (1998)

The pathogenesis of human cerebral malaria (CM) remains unresolved. In the most widely used murine model of CM, the presence of T lymphocytes and/or interferon (IFN)-gamma is a prerequisite. IFN-gamma is the key inducer of indoleamine 2,3-dioxygenase (IDO), which is the catalyst of the first, and rate-limiting, step in the metabolism of tryptophan (Trp) along the kynurenine (Kyn) pathway. Quinolinic acid (QA), a product of this pathway, is a neuro-excitotoxin, like glutamic acid (Glu) and aspartic acid (Asp). Kynurenic acid (KA), also produced from the Kyn pathway, antagonizes the neuro-excitotoxic effects of QA, Glu, and Asp. We therefore examined the possible roles of IDO, metabolites of the Kyn pathway, Glu, and Asp in the pathogenesis of fatal murine CM. Plasmodium berghei ANKA infection was studied on days 6 and 7 post-inoculation (p.i.), at which time the mice exhibited cerebral symptoms such as convulsions, ataxia, coma, and a positive Wooly/White sign and died within 24 hours. A model for noncerebral malaria (NCM), P. berghei K173 infection, was also studied on days 6 and 7 and 13 to 17 p.i. to examine whether any changes were a general response to malaria infection. Biochemical analyses were done by high-pressure liquid chromatography and gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS). IDO activity was low or absent in the brains of uninfected mice and NCM mice (days 6 and 7 p.i.) and was induced strongly in the brains of fatal murine CM mice (days 6 and 7 p.i.) and NCM animals (days 13 to 17 p.i.). This induction was inhibited greatly by administration of dexamethasone, a treatment that also prevented CM symptoms and death. Furthermore, IDO induction was absent in IFN-gamma gene knockout mice, which were also resistant to CM. Brain concentrations of Kyn, 3-hydroxykynurenine, and the neuro-excitotoxin QA were significantly increased in both CM mice on days 6 and 7 p.i. and NCM mice on days 13 to 17 p.i., whereas an increase in the ratio of brain QA to KA occurred only in the CM mice at the time they were exhibiting cerebral symptoms. Brain concentrations of Glu and Asp were significantly decreased in CM and NCM mice (days 13 to 17 p.i.). The results imply that neuro-excitation induced by QA may contribute to the convulsions and neuro-excitatory signs observed in CM.
Intestinal Tolerance Is Converted to Autoimmune Enteritis upon PD-1 Ligand Blockade (2009)

The B7 family member programmed death-1 ligand (PD-L1) has been shown to play an inhibitory role in the regulation of T cell responses in several organs. However, the role of PD-L1 in regulating tolerance to self-Ags of the small intestine has not been previously addressed. In this study, we investigated the role of PD-L1 in CD8(+) T cell tolerance to an intestinal epithelium-specific Ag using the iFABP-tOVA transgenic mouse model, in which OVA is expressed as a self-Ag throughout the small intestine. Using adoptive transfer of naive OVA-specific CD8(+) T cells, we show that loss of PD-1:PD-L1 signaling, by either Ab-mediated PD-L1 blockade or transfer of PD-1(-/-) T cells, leads to considerable expansion of OVA-specific CD8(+) T cells and their differentiation into effector cells capable of producing proinflammatory cytokines. A fatal CD8(+) T cell-mediated inflammatory response develops rapidly against the small bowel causing destruction of the epithelial barrier, severe blunting of intestinal villi, and recruitment and activation of myeloid cells. This response is highly specific because immune destruction selectively targets the small intestine but not other organs. Collectively, these results indicate that loss of the PD-1:PD-L1 inhibitory pathway breaks CD8(+) T cell tolerance to intestinal self-Ag, thus leading to severe enteric autoimmunity.
Cannabis: pharmacology and toxicology in animals and humans (1996)

Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (delta 9-THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to delta 9-THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty-acid derived compound that possesses pharmacological properties similar to delta 9-THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid-derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids.
Development and Validation of the Clinical Anxiety Scale: A Rapid Assessment Instrument for Empirical Practice (1989)

The development and validation of a new rapid assessment instrument, the Clinical Anxiety Scale (CAS), is described. The CAS has good reliability and validity and is compatible in format with a number of other rapid assessment instruments designed for human service professionals who wish to evaluate the effects of their interventions with clients experiencing dysfunctional anxiety.
Enzymatic characterization of beta D-galactoside alpha2 leads to 3 sialyltransferase from porcine submaxillary gland. (1979)

The substrate requirements, linkage specificity, and kinetic mechanism of a pure sialyltransferase from porcine submaxillary glands have been examined. The enzyme transfers sialic acid from the donor nucleotide, CMP-NeuAc, into the sequence NeuAcalpha2 leads to 3Galbeta1 leads to 3GalNAc, which is found in both glycoproteins and gangliosides. It forms only the alpha2 leads to 3 linkage with the disaccharide Gal/beta1 leads to 3GalNAc or antifreeze glycoprotein, which, along with asialoglycoproteins containing the sequence Gal/beta1 leads to 3GalNAcalpha1 leads to O-Thr/Ser, are the best acceptor substrates. Low molecular weight galactosides linked beta1 leads to 3 to glycose residues other than N-acetylgalactosamine are poor acceptors with relatively high Km values, while those in beta1 leads to 4 or beta1 leads to 6 linkages have both high Km and low Vmax. With glycoprotein and ganglioside acceptors this substrate specificity appears to be even more strict, with the sequence Gal/beta1 leads to 3GalNAc serving as the exclusive acceptor. Thus the present enzyme is not responsible either for the sequence, NeuAcalpha2 leads to 3Galbeta1 leads to 4GlcNAc, found in the asparagine-linked chains of certain glycoproteins, or for the synthesis of hematoside, NeuAcalpha2 leads to 3Galbeta1 leads to 4Glcbeta1 leads to 1Cer. Initial rate kinetic studies, with and without inhibitors, suggest that the transferase has an equilibrium random order mechanism.
Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer (2006)

These results demonstrate that proliferation and apoptosis are altered not only in preneoplastic lesions but also in apparently normal looking epithelium associated with cancer. Luminal cell expression of Mcm-2 appears to be particularly promising as a marker of high-risk normal epithelium. The role of apoptotic markers such as activated caspase-3 is more complex, and might depend on the proliferation status of the tissue in question.