gebhart/patrepeval huggingface dataset:
Neurophatic Pain Treatment: The Challenge (2003)

Abstract: Neuropathic pain covers a heterogeneous group of pain conditions characterized by a primary lesion or dysfunction of the sensory nervous system. Its pathophysiology is not yet clear, but neuronal hyperexcitability in those neurons that have lost their normal patterned input seems to be a common denominator for neuropathic pain. A mechanism‐based approach is being developed, but still the clinical workup is being based on the anatomical location and the determination of an underlying cause. In addition, clinicians are presented with a challenge because neuropathic pain does not respond well to traditional pain therapies and there are greater individual variations in pain responsiveness. A number of drug classes have been evaluated in the treatment of neuropathic pain syndromes; these are mainly drugs developed for other nervous system diseases, although their precise action and whether their action is central or peripheral remains unknown for the majority of them. First‐line agents used in the treatment of neuropathic pain conditions are tricyclic antidepressants and anticonvulsants, especially carbamazepine and gabapentin. Novel therapies are currently being developed for neuropathic pain that are based in experimental models and theoretical frameworks on the pathosphysiological events that initiate this type of pain.
Potential role of Th17 cells in the pathogenesis ofinﬂammatory bowel disease (2009)

The etiopathology of inflammatory bowel disease (IBD) remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation. IBD including Crohn's disease (CD) and ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Th1-mediated inflammatory disorder while UC is regarded as a Th2-like disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Th1 or Th2 cells, and several cytokines [e.g. interleukin (IL)-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.
Capillary isoelectric focusing of hemoglobin variants in the pediatric clinical laboratory (1997)

We have used capillary isoelectric focusing (cIEF) to diagnose and monitor hemoglobinopathies in children for over three years. This report describes a major revision of our original method (Clin. Chem. 1994, 40, 2288-2295) that improves the analysis of hemoglobin (Hb) variants by cIEF, especially capillary performance and quantitation precision for minor variants. The revised method uses mixed ampholytes (2% pH 6-8:3-10; 10:1), lower viscosity methylcellulose (0.375%) solution, between-sample capillary conditioning with methanol, and hemolysates prepared from red blood cells (RBC) instead of whole blood. Collectively, these changes prolonged capillary life by minimizing capillary exposure to NaOH, standardized the sample matrix, and improved the precision of peak autointegration. The between-run quantitation imprecision (% relative standard deviation) of the revised method was 0.1-3.5% for all diagnostically important major and minor Hb variants present at normal or abnormal levels. The results show the use of the revised method for (i) posttranslationally modified Hb present at low concentrations in normal blood, (ii) Hb oxidation products produced by improper sample storage, (iii) differential diagnosis of S/beta + thalassemia, G-Philadelphia trait, S/C-Harlem disease, and Hb H disease, (iv) sensitive detection of minor variants like Hb A2' as indicators of an alpha globin mutation, and (v) neonatal screening using dried blood collected on filter paper. The results show that high-efficiency separation and precise quantitation of Hb variants over a wide range of concentrations makes cIEF a comprehensive assay that can be used without adjunct analyses for the automated primary evaluation of hemoglobinopathies and thalassemias.
Scavenger Receptor-BI Inhibits ATP-binding Cassette Transporter 1- mediated Cholesterol Efflux in Macrophages (2000)

Scavenger receptor BI (SR-BI) facilitates the efflux of cellular cholesterol to plasma high density lipoprotein (HDL). Recently, the ATP-binding cassette transporter 1 (ABC1) was identified as a key mediator of cholesterol efflux to apolipoproteins and HDL. The goal of the present study was to determine a possible interaction between the SR-BI and ABC1 cholesterol efflux pathways in macrophages. Free cholesterol efflux to HDL was increased ( approximately 2.2-fold) in SR-BI transfected RAW macrophages in association with increased SR-BI protein levels. Treatment of macrophages with 8-bromo-cAMP (cAMP) resulted in a 4.1-fold increase in ABC1 mRNA level and also increased cholesterol efflux to HDL (2.2-fold) and apoA-I (5.5-fold). However, in SR-BI transfected RAW cells, cAMP treatment produced a much smaller increment in cholesterol efflux to HDL (1.1-fold) or apoA-I (3.3-fold) compared with control cells. In macrophages loaded with cholesterol by acetyl-LDL treatment, SR-BI overexpression did not increase cholesterol efflux to HDL but did inhibit cAMP-mediated cholesterol efflux to apoA-I or HDL. SR-BI neutralizing antibody led to a dose- and time-dependent increase of cAMP-mediated cholesterol efflux in both SR-BI transfected and control cells, indicating that SR-BI inhibits ABC1-mediated cholesterol efflux even at low SR-BI expression level. Transfection of a murine ABC1 cDNA into 293 cells led to a 2.3-fold increase of cholesterol efflux to apoA-I, whereas co-transfection of SR-BI with ABC1 blocked this increase in cholesterol efflux. SR-BI and ABC1 appear to have distinct and competing roles in mediating cholesterol flux between HDL and macrophages. In nonpolarized cells, SR-BI promotes the reuptake of cholesterol actively effluxed by ABC1, creating a futile cycle.
Real-Time PCR (2004)

The development of instruments that allow real-time monitoring of fluorescence within PCR reaction vessels is a significant advance in clinical bacteriology. The technology is very flexible, and many alternative instruments and fluorescent probe systems are currently available. Real-time PCR assays can be completed very rapidly, because no manipulations are required after amplification. Identification of amplification products by probe detection in real time is highly accurate compared with size analysis on gels. Analysis of the progress of the reaction allows accurate quantification of the target sequence over a very wide dynamic range, provided suitable standards are available. Finally, probe melting analysis can detect sequence variants including single base mutations.
Synthesis of Fine Cubic Li7La3Zr2O12 Powders in Molten LiCl–KCl Eutectic and Facile Densification by Reversal of Li+/H+ Exchange (2018)

Recently, solid-state electrolytes have been a highly active area of research for future Li-ion batteries due to the potential for drastically improved energy density and safety. Among these materials, garnet structured lithium lanthanum zirconate (Li7La3Zr2O12, LLZO) shows particular promise owing to the high ionic conductivity of its cubic polymorph, inertness, and electrochemical stability against metallic lithium. Herein we report the facile preparation of phase-pure, cubic LLZO via molten salt synthesis in a eutectic mixture of LiCl–KCl at 900 °C. Fine powders of Al- and Ga-doped LLZO were obtained with primary particle sizes ranging from 0.3 to 3 μm. Depending on the consolidation conditions, pellets with up to 86% relative density could be obtained, with Li+ conductivity values ranging from 0.230 to 0.371 mS cm–1. It is also observed that while the effect of hydration has a profoundly deleterious effect on sintering and densification, this effect can be mitigated by the simple addition of LiOH before sintering to reverse hydration and aid densification. Qualitative discussions on the mechanisms of LLZO formation in the molten salt medium are discussed, in addition to implications for scalable processing of LLZO electrolytes.
Biosynthesis of phosphatidylinositol-glycan (PI-G)-anchored membrane proteins in cell-free systems: PI-G is an obligatory cosubstrate for COOH-terminal processing of nascent proteins. (1992)

It is generally recognized that nascent proteins destined to be processed to a phosphatidylinositol-glycan (PI-G)-anchored membrane form contain a hydrophobic signal peptide at both their NH2 and COOH termini. In previous studies we showed that rough microsomal membranes (RM) prepared from CHO cells can carry out COOH-terminal processing. We have now investigated RM prepared from many additional cell types, including frog oocytes, B cells, and T cells, and found that all are competent with respect to COOH-terminal processing. Exceptions were certain mutant T cells that had been shown to be defective at various steps of PI-G anchor biosynthesis [Sugiyama, E., De Gasperi, R., Urakaze, M., Chang, H.-M., Thomas, L. J., Hyman, R., Warren, C. D. & Yeh, E. T. H. (1991) J. Biol. Chem. 266, 12119-12122]. In one such defective mutant, COOH-terminal processing activity of RM could be restored either by transfecting the intact cells with the gene for the deficient step in PI-G synthesis or by adding PI-G extracts to the RM in vitro. Cleavage of the COOH-terminal signal peptide in the RM is therefore dependent on the presence of intact PI-G incorporated into the mature protein.
Modification of porous poly(ether sulfone) membranes by low‐temperature CO2‐plasma treatment (2002)

Abstract A general method of modifying the entire cross section of porous poly(ether sulfone) membranes with a low‐temperature CO 2 ‐plasma treatment is reported. Both surfaces of the membranes are highly hydrophilic, with a water drop on the surface disappearing in less than 1 s, even 6 months after plasma treatment. This high hydrophilicity of both membrane surfaces results from the incorporation of hydrophilic functionalities, as evidenced by Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy. The incorporation of these hydrophilic functionalities takes place primarily during plasma treatment, with some incorporation of atmospheric oxygen and nitrogen immediately upon exposure to air. Scanning electron microscopy shows that the membrane surface is covered by a thin, white layer that is likely the result of etching and redeposition of sputtered surface fragments. An increase in the water bubble point and glass‐transition temperature is also observed for CO 2 ‐plasma‐treated membranes. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 2473–2488, 2002
Regulation of Endocytosis of Activin Type II Receptors by a Novel PDZ Protein through Ral/Ral-binding Protein 1-dependent Pathway (2002)

Using yeast two-hybrid screening, we have identified a mouse Postsynaptic density 95/Discs large/Zona occludens-1 (PDZ) protein that interacts with activin type II receptors (ActRIIs). We named the protein activin receptor-interacting protein 2 (ARIP2). ARIP2 was found to have one PDZ domain in the NH(2)-terminal region and interact specifically with ActRIIs among the receptors for the transforming growth factor beta family by the PDZ domain. Interestingly, overexpression of ARIP2 enhances endocytosis of ActRIIs and reduces activin-induced transcription in Chinese hamster ovary K1 cells. In addition, immunofluorescence co-localization studies indicated the direct involvement of ARIP2 in the intracellular translocation of ActRIIs by PDZ domain-mediated interaction. Moreover, we have identified that the COOH-terminal region of ARIP2 interacts with Ral-binding protein 1 (RalBP1). RalBP1 is a potential effector protein of small GTP-binding protein Ral and regulates endocytosis of epidermal growth factor and insulin receptors. The studies using deletion mutants of RalBP1 and constitutively GTP and GDP binding forms of Ral indicate that ARIP2 regulates endocytosis of ActRIIs through the Ral/RalBP1-dependent pathway, and the GDP-GTP exchange of Ral is critical for this regulation.
Relationship between Hemolytic Activity and Adsorption Capacity of Aluminum Hydroxide and Calcium Phosphate as Immunological Adjuvants for Biologicals (1994)

Aluminum hydroxide (Al) and calcium phosphate (Ca) gels have been used as vaccine adjuvants for many years. We investigated mechanism of the hemolytic activities of both adjuvant materials. The hemolytic activity of each gel depended on the gel dose. The adsorption capacities and the hemolytic activities of both adjuvants decreased as the concentration of phosphate increased in a gel-washing solution. A positive correlation between the hemolytic activity and the adsorption capacity was found in Al-gel. A disruptive effect of Ca-gel on membrane of erythrocytes was shown by electron microscopy. Ca-gel required more than 10 times as much pre-adsorbed ovalbumin as did Al-gel to inhibit the hemolysis. These results suggest that the hemolytic activity of both adjuvant materials depended mainly on the adsorption ability, and it may be useful to control the adsorption ability of adjuvants to reduce their hemolytic activity.
Direct anonymous attestation (2004)

This paper describes the direct anonymous attestation scheme (DAA). This scheme was adopted by the Trusted Computing Group (TCG) as the method for remote authentication of a hardware module, called Trusted Platform Module (TPM), while preserving the privacy of the user of the platform that contains the module. DAA can be seen as a group signature without the feature that a signature can be opened, i.e., the anonymity is not revocable. Moreover, DAA allows for pseudonyms, i.e., for each signature a user (in agreement with the recipient of the signature) can decide whether or not the signature should be linkable to another signature. DAA furthermore allows for detection of "known" keys: if the DAA secret keys are extracted from a TPM and published, a verifier can detect that a signature was produced using these secret keys. The scheme is provably secure in the random oracle model under the strong RSA and the decisional Diffie-Hellman assumption.
Assessment of the Ability of the Bioelectric Effect To Eliminate Mixed-Species Biofilms (2005)

Microbes have been able to persist in water distribution systems through the development of multicellular communities known as biofilms. This study evaluated the usefulness of the bioelectric effect for the elimination of water distribution system biofilms from annular reactors. The bioelectric effect did not have any bactericidal action either alone or when coupled with free chlorine.
Preparation and Properties of a Heat‐Treated Human Plasma Protein Fraction (1957)

Summary By precipitating a particular mixture of albumins and globulins from an Effluent IV‐1 prepared by a modified fractionation procedure, a safe and osmotically active fraction was obtained from human plasma in high yield. The HTPF thus obtained is devoid of cat depressor activity. Both fibrinogen and gamma globulin can be recovered from plasma by the method described. Technical details concerning the preparation of HTPF are given. Results of physico‐chemical measurements show that during heating at 60°C. for over 10 hours little change occurs to the proteins present in HTPF. Pharmacological data show HTPF to be an effective plasma volume expander. Résumé Par précipitation d'un mélange particulier d'albumines et de globulines provenant d'un Effluent IV‐1 préparé par un procédé de fractionnement modifié, les auteurs ont pu obtenir à grand rendement une fraction de plasma humain ne présentant pas de danger de transmission de l'hépatite et d'une activité osmotique satisfaisante. Cette HTPF (heat‐treated plasma fraction) est dépourvue d'effet dépresseur chez le chat. La méthode employée pour l'obtenir permet aussi de récupérer la fibrinogène et la gammaglobuline. Les détails technique de la méthode sont décrits. L'analyse physio‐chimique a montré qu'après 10 heures de chauffage à 60° les protéines présentes dans l'HTPF ont été à peine modifiées. Des études pharmacologiques il ressort que l'HTPF est un expanseur plasmatique efficace. Zusammenfassung Durch Ausfällen einer Albumin‐Globulin‐Mischung aus einem nach einer modifizierten Fraktionierungsmethode gewonnenen Eluat IV‐1 gelingt es, aus menschlichem Mischplasma eine pasteurisierbare und daher hepatitissichere Fraktion mit hoher osmotischer Aktivität in guter Ausbeute zu gewinnen. Diese als HTPF bezeichnete Lösung zeigt an der Katze keine Depressoraktivität. Als Nebenprodukte können bei diesem Verfahren aus dem Plasma Fibrinogen und Gamma‐globulin gewonnen werden. Die technische Herstellung von HTPF wird eingehend beschrieben. Physikochemische Untersuchungen zeigten, daß die im HTPF enthaltenen Proteine durch die Pasteurisation nur unbedeutende Veränderungen erleiden. Pharmakologische Untersuchungen zeigten, daß HTPF ein wirksames Präparat zur Kreislauffüllung darstellt.
Current Advancements in Addressing Key Challenges of Therapeutic Antibody Design, Manufacture, and Formulation (2019)

Therapeutic antibody technology heavily dominates the biologics market and continues to present as a significant industrial interest in developing novel and improved antibody treatment strategies. Many noteworthy advancements in the last decades have propelled the success of antibody development; however, there are still opportunities for improvement. In considering such interest to develop antibody therapies, this review summarizes the array of challenges and considerations faced in the design, manufacture, and formulation of therapeutic antibodies, such as stability, bioavailability and immunological engagement. We discuss the advancement of technologies that address these challenges, highlighting key antibody engineered formats that have been adapted. Furthermore, we examine the implication of novel formulation technologies such as nanocarrier delivery systems for the potential to formulate for pulmonary delivery. Finally, we comprehensively discuss developments in computational approaches for the strategic design of antibodies with modulated functions.
Studies in the Pyrazole Series. III. Substituted Guanidines1,2 (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies in the Pyrazole Series. III. Substituted Guanidines1,2F. L. Scott, D. G. O'Donovan, and J. ReillyCite this: J. Am. Chem. Soc. 1953, 75, 16, 4053–4054Publication Date (Print):August 1, 1953Publication History Published online1 May 2002Published inissue 1 August 1953https://pubs.acs.org/doi/10.1021/ja01112a051https://doi.org/10.1021/ja01112a051research-articleACS PublicationsRequest reuse permissionsArticle Views691Altmetric-Citations40LEARN 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
Ghrelin prevents levodopa‐induced inhibition of gastric emptying and increases circulating levodopa in fasted rats (2012)

Ghrelin counteracts L-dopa-induced delayed gastric emptying but not Fos induction in the brain and enhances circulating L-dopa levels. Potential therapeutic benefits of ghrelin agonists in Parkinson's disease patients treated with L-dopa remain to be investigated.
Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis (2009)

The very promising results seen so far in patients with severe systemic JIA and acceptable tolerability gives tocilizumab a central role in the future therapy in controlling this disease. No other biological therapy has achieved similar high response rates when treating with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but direct comparison of the efficacy of different biological agents are not yet available.
Resonant link bidirectional power converter without electrolytic capacitor (2002)

A power converter that consists of two identical three-phase pulse-width modulation (PWM) modulators and a novel resonant circuit is presented. The zero-switching-loss PWM power converter and the resonant circuit are presented. The resonant circuit is capable of PWM operation with minimum DC bus voltage stresses and minimum peak resonant current. The new control strategy is integrated to realize a bidirectional power converter without an electrolytic link capacitor. The power flow between converters is bidirectional, and regenerative braking is inherent. The source side currents maintain sinusoidal waveforms with unity power factor. It was observed in the experiment that the resonant circuit guarantees the soft switching of the converter power devices. In addition, by balancing the active power between the source and load side, the voltage across a small ceramic link capacitor can be maintained within a small deviation from the reference. Simulation results and experimental results are presented to verify the operational principles.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Macrophage-derived Growth Factors in Wound Healing: Regulation of Growth Factor Production by the Oxygen Microenvironment (1989)

There is a large amount of current research investigating the pathophysiologic aspects of pulmonary hypertension. Results of this research indicate the potential role of the macrophage as one possible mediator of pulmonary hypertension. The macrophage has been shown to produce numerous soluble mediators, including various growth factors, some of which may be involved in the cellular proliferation of the arterial wall. Most of the knowledge regarding oxygen microenvironments, macrophages, and growth factor production comes from research on the healing wound. A considerable amount of what has been learned about the role of the macrophage in cutaneous wound healing may have direct applicability to macrophage function in acute lung injury and repair, and pulmonary hypertension. Macrophages play a pivotal role in cutaneous wound repair. They participate in immunologic and nonspecific host defense responses and produce numerous growth factors that regulate mesenchymal cell proliferation, migration, and synthesis of extracellular matrix proteins. These same responses are probably at work during the progression of pulmonary hypertension.