gebhart/patrepeval huggingface dataset:
Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation (2004)

Lysosomal cysteine proteases are a family comprising > 10 enzymes. For many years it was believed that these enzymes catalyse protein breakdown unselectively, are highly redundant in their substrate specificity and are also expressed ubiquitously. This view has changed dramatically since a number of new lysosomal cysteine proteases with restricted expression and outstanding enzymatic activity have been described. In addition, knockout mice and selective protease inhibitors have been used to characterise specific functions of single proteases. In this review, some of these functions are discussed in relation to the lungs, especially the role of lysosomal cysteine proteases in matrix remodelling, immunoregulation and surfactant protein processing.
Materials and Transducers Toward Selective Wireless Gas Sensing (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMaterials and Transducers Toward Selective Wireless Gas SensingRadislav A. Potyrailo*, Cheryl Surman, Nandini Nagraj, and Andrew BurnsView Author Information General Electric Global Research Center, Niskayuna, New York, USAE-mail: [email protected].Cite this: Chem. Rev. 2011, 111, 11, 7315–7354Publication Date (Web):September 7, 2011Publication History Received7 February 2011Published online7 September 2011Published inissue 9 November 2011https://pubs.acs.org/doi/10.1021/cr2000477https://doi.org/10.1021/cr2000477review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views10036Altmetric-Citations243LEARN 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 SUBJECTS:Carbon nanotubes,Humidity,Materials,Polymers,Sensors Get e-Alerts
Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro. (1995)

Natural killer (NK) cells are large granular lymphocytes that constitutively express functional IL-2 receptors. We have shown that recombinant human IL-15 uses the IL-2 receptor to activate human NK cells and can synergize with recombinant human IL-12 to stimulate NK cell production of IFN-gamma in vitro. IFN-gamma production by NK cells is critical in the prevention of overwhelming infection by obligate intracellular microbial pathogens in several experimental animal models. Herein, we demonstrate that human monocytes produce IL-15 protein within 5 h of activation with LPS. Using an IL-15-neutralizing antiserum in a coculture of LPS-activated monocytes and NK cells, we demonstrate that monocyte-derived IL-15 is critical for optimal NK cell production of IFN-gamma. Endogenous IL-15 activates NK cells through the IL-2 receptor, and with endogenous IL-12, regulates NK cell IFN-gamma after monocyte activation by LPS. These in vitro studies are the first to characterize a function for endogenous IL-15, and as such, suggest an important role for IL-15 during the innate immune response. IL-15 may be an important ligand for the NK cell IL-2 receptor in vivo.
Nucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivatives (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivativesRonald P. Glinski, M. Sami Khan, Richard L. Kalamas, and Michael B. SpornCite this: J. Org. Chem. 1973, 38, 25, 4299–4305Publication Date (Print):December 1, 1973Publication History Published online1 May 2002Published inissue 1 December 1973https://pubs.acs.org/doi/10.1021/jo00964a020https://doi.org/10.1021/jo00964a020research-articleACS PublicationsRequest reuse permissionsArticle Views563Altmetric-Citations63LEARN 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
Redox-transfer. Part VI. Determination of Hammett's ρ-constant for the oxidation of cuprous chloride by aromatic sulphonyl chlorides (1969)

The copper chloride-catalyzed redox-transfer chain addition of styrene to aromatic sulphonyl chlorides which carry substituents with a wide range of Hammett σ-values, has been studied by dilatometry at 110° with acetonitrile as the solvent. When an excess of styrene is used, the rate of the overall addition is governed by the slowest step of the chain propagation, i.e. the oxidation of cuprous chloride by sulphonyl chloride. Hammett's equation is obeyed for this reaction, and gives a ρ-value of 0·565. This is the first time that Hammett's equation has been shown to be valid for the homolytic abstraction of an atom other than hydrogen. The overall addition is first-order in copper chloride up to 5 × 10–3M, and in sulphonyl chloride up to at least 70% conversion.
Real time quantification in plasma of human telomerase reverse transcriptase (hTERT) mRNA in patients with colorectal cancer (2004)

These results show that detection of mRNA based on the qRT-PCR of the telomerase hTERT(N) gene in plasma clearly differentiates between healthy and colorectal cancer patients and that hTERT(N) can be detected and quantified in plasma. This opens up a new field as a noninvasive blood test for colorectal cancer diagnosis.
Protective and Therapeutic Effect of the Indonesian Medicinal HerbCurcuma xanthorrhizaon β-D-Galactosamine-induced Liver Damage (1996)

The present study was carried out to investigate the hepatoprotective effects of a dose of C. xanthorrhiza on acute hepatotoxicity induced in rats by a single dose of β-D-galactosamine (288 mg/kg, i.p.), and its mechanism of action. C. xanthorrhiza (100 mg/kg) was administered p.o. to experimental animals according to the protocol followed by the i.p. administration of a single dose of hepatotoxin. Hepatoprotective activity was monitored by estimating serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels and histopathological changes in the livers of C. xanthorrhiza -treated and untreated groups of animals. The results clearly indicated that the extract of C. xanthorrhiza significantly reduced the acute elevation of serum transaminases induced by hepatotoxin, and alleviated the degree of liver damage at 24 h after the intraperitoneal administration of the hepatotoxins.
The EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment (2017)

Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous antitumor response, immune regulatory pathways can subvert the effector phase and enable tumor escape. Negative regulatory pathways include extrinsic suppression mechanisms, but also a T cell-intrinsic dysfunctional state. A more detailed study has been hampered by a lack of cell surface markers defining tumor-specific dysfunctional TILs, and PD-1 alone is not sufficient. Recently, we identified the transcription factor Egr2 as a critical component in controlling the anergic state in vitro. In this study, we show that the Egr2-driven cell surface proteins LAG-3 and 4-1BB can identify dysfunctional tumor antigen-specific CD8<sup>+</sup> TIL. Co-expression of 4-1BB and LAG-3 was seen on a majority of CD8<sup>+</sup> TILs, but not in lymphoid organs. Functional analysis revealed defective IL-2 and TNF production yet retained expression of IFN-γ and regulatory T cell-recruiting chemokines. Transcriptional and phenotypic characterization revealed coexpression of multiple additional co-stimulatory and co-inhibitory receptors. Administration of anti-LAG-3 plus anti-4-1BB mAbs was therapeutic against tumors in vivo, which correlated with phenotypic normalization. Our results indicate that coexpression of LAG-3 and 4-1BB characterize dysfunctional T cells within tumors, and that targeting these receptors has therapeutic utility.
Randomized trial of interferon β-1a in chronic inflammatory demyelinating polyradiculoneuropathy (1999)

This trial shows that IFN-beta is safe but not efficacious in treatment-resistant CIDP.
Functional brain imaging of swallowing: An activation likelihood estimation meta‐analysis (2008)

A quantitative, voxel-wise meta-analysis was performed to investigate the cortical control of water and saliva swallowing. Studies that were included in the meta-analysis (1) examined water swallowing, saliva swallowing, or both, and (2) reported brain activation as coordinates in standard space. Using these criteria, a systematic literature search identified seven studies that examined water swallowing and five studies of saliva swallowing. An activation likelihood estimation (ALE) meta-analysis of these studies was performed with GingerALE. For water swallowing, clusters with high activation likelihood were found in the bilateral sensorimotor cortex, right inferior parietal lobule, and right anterior insula. For saliva swallowing, clusters with high activation likelihood were found in the left sensorimotor cortex, right motor cortex, and bilateral cingulate gyrus. A between-condition meta-analysis revealed clusters with higher activation likelihood for water than for saliva swallowing in the right inferior parietal lobule, right postcentral gyrus, and right anterior insula. Clusters with higher activation likelihood for saliva than for water swallowing were found in the bilateral supplementary motor area, bilateral anterior cingulate gyrus, and bilateral precentral gyrus. This meta-analysis emphasizes the distributed and partly overlapping cortical networks involved in the control of water and saliva swallowing. Water swallowing is associated with right inferior parietal activation, likely reflecting the sensory processing of intraoral water stimulation. Saliva swallowing more strongly involves premotor areas, which are crucial for the initiation and control of movements.
Multi‐Center Evaluation of Bioabsorbable Collagen Membrane for Guided Tissue Regeneration in Human Class II Furcations (1996)

Clinical data related to GTR therapy for Class II furcations were analyzed from 7 treatment centers that evaluated one of two possible treatment pairs, either bioabsorbable collagen membrane (Type I bovine tendon collagen) (COLL) versus control surgical debridement (DEBR) or COLL versus expanded polytetrafluoroethylene (ePTFE). After initial preparation and re-evaluation, full thickness flaps were reflected, the defects debrided, and the roots planed. Furcations and associated bony defects in each patient were randomly assigned to one of the 2 treatments in each pair, and the flaps closed. Patients received quarterly periodontal maintenance until surgical re-entry at 6 to 12 (mean 11.1) months. Data from 59 pairs of Class II furcations were analyzed via paired t, Wilcoxon signed rank, and RM ANOVA tests. COLL showed better results than DEBR for vertical defect fill, percent defect resolution, and horizontal furcation fill. When COLL was compared to ePTFE in furcations across patients, no differences were found. Both COLL and ePTFE resulted in an improvement in clinical furcation Class about 50% of the time (compared to 7% frequency with DEBR). COLL use yielded 8 and ePTFE yielded 1 clinically-complete furcation closures. COLL barriers resulted in generally favorable clinical results in furcation defects, appeared to be better than DEBR alone, and were at least similar to and often better than ePTFE. COLL of the type used in this study appears to be a useful and beneficial material for regenerative therapy in Class II furcation type periodontal defects.
Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses (1993)

We constructed recombinant vaccinia virus vectors for expression of the structural region of hepatitis C virus (HCV). Infection of mammalian cells with a vector (vv/HCV1-906) encoding C-E1-E2-NS2 generated major protein species of 22 kDa (C), 33 to 35 kDa (E1), and 70 to 72 kDa (E2), as observed previously with other mammalian expression systems. The bulk of the E1 and E2 expressed by vv/HCV1-906 was found integrated into endoplasmic reticulum membranes as core-glycosylated species, suggesting that these E1 and E2 species represent intracellular forms of the HCV envelope proteins. HCV E1 and E2 formed E1-E2 complexes which were precipitated by either anti-E1 or anti-E2 serum and which sedimented at approximately 15 S on glycerol density gradients. No evidence of intermolecular disulfide bonding between E1 and E2 was detected. E1 and E2 were copurified to approximately 90% purity by mild detergent extraction followed by chromatography on Galanthus nivalus lectin-agarose and DEAE-Fractogel. Immunization of chimpanzees with purified E1-E2 generated high titers of anti-E1 and anti-E2 antibodies. Further studies, to be reported separately, demonstrated that purified E1-E2 complexes were recognized at high frequency by HCV+ human sera (D. Y. Chien, Q.-L. Choo, R. Ralston, R. Spaete, M. Tong, M. Houghton, and G. Kuo, Lancet, in press) and generated protective immunity in chimpanzees (Q.-L. Choo, G. Kuo, R. Ralston, A. Weiner, D. Chien, G. Van Nest, J. Han, K. Berger, K. Thudium, J. Kansopon, J. McFarland, A. Tabrizi, K. Ching, B. Mass, L. B. Cummins, E. Muchmore, and M. Houghton, submitted for publication), suggesting that these purified HCV envelope proteins display native HCV epitopes.
Pharmacokinetic and Tumor Distribution Characteristics of Temsirolimus in Patients with Recurrent Malignant Glioma (2007)

Drugs that induce cytochrome P450 3A4, such as EIAEDs, significantly affect the pharmacokinetics of temsirolimus and its active metabolite, sirolimus. Total exposure to temsirolimus and sirolimus was lower in the EIAED group at the maximum tolerated dose of 250 mg compared with the non-EIAED group at the maximum tolerated dose of 170 mg. However, brain tumor tissue concentrations of temsirolimus and sirolimus were relatively comparable in both groups of patients at their respective dose levels. Correlative analyses of the tissue for the inhibition of the key regulators (p70S6 kinase and 4E-binding protein 1) of mammalian target of rapamycin are necessary to define the therapeutic significance of the altered exposure to temsirolimus.
Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans (2011)

We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans.
Biochemical and Physicochemical Properties of Phosphorodithioate DNA (1996)

The biochemical and physicochemical properties of DNA oligomers containing phosphorodithioate linkages in various configurations were evaluated. Duplex stability studies, which were carried out by thermal denaturation analysis with complementary unmodified DNA, indicated a highly cooperative process similar to completely unmodified duplexes. Oligomers containing phosphorodithioate linkages were found to have reduced melting temperatures relative to unmodified duplexes, with the degree of Tm depression paralleling the percent phosphorodithioate composition of the oligomer. Relative to activation of RNase H, DNA oligomers containing up to 50% phosphorodithioate linkages were able to direct RNase H degradation with the same efficiency as unmodified DNA while those containing from 50 to 100% acted with somewhat reduced efficiency. At limiting concentrations, an oligomer containing alternating phosphorodithioate and phosphate linkages was able to direct RNase H degradation of the target RNA in an extended incubation, while an unmodified oligomer did not. The nuclease resistance of phosphorodithioate-containing oligomers was evaluated in HeLa cell nuclear and cytoplasmic extracts, in human serum, and with nucleases S1 and DNase I. Oligomers containing alternating phosphorodithioate and phosphate were highly resistant to degradation in all systems. However, oligomers having more than one unmodified linkage separating phosphorodithioates were degraded rapidly by DNase I, while demonstrating stability to degradation in all other systems tested. These results indicate that phosphorodithioate-containing DNA oligomers are highly nuclease-resistant, are able to form stable duplexes with complementary nucleic acid sequences, and efficiently direct RNase H degradation of target RNA.
Accelerated Titration Designs for Phase I Clinical Trials in Oncology (1997)

Accelerated titration (i.e., rapid intrapatient drug dose escalation) designs appear to effectively reduce the number of patients who are under-treated, speed the completion of phase I trials, and provide a substantial increase in the information obtained.
Barrier height reduction of the Schottky barrier diode using a thin highly doped surface layer (1980)

The interfacial layer theory considering the effects of the interface states and surface fixed charges is developed for the barrier height of the Schottky barrier diode with a thin uniformly doped surface layer. It is shown that the origins of the barrier height modification using the highly doped surface layer are mainly due to the increase of the electric field at the contact surface and the change of the interface properties. Design criterion for the maximum width of the highly doped surface layer is derived and calculated in detail for nickel barrier metal on n-type silicon with the specificed interfacial layer conditions. Comparisons between the the developed expression of the barrier height reduction with respect to the ion dose and the experimental data of Shannon et al. are made, which tend to support the proposed model.
Mutanolysin, Bacteriolytic Agent for Cariogenic Streptococci: Partial Purification and Properties (1974)

Mutanolysin partially purified from the culture filtrate of Streptomyces globisporus 1829 consists of two main lytic enzymes with an isoelectric point near pH 8.5 and 10, respectively, and proteolytic enzyme is associated with the latter lytic enzyme. Mutanolysin exhibited maximal lytic activity at 60 C in the pH range 6.5 to 7.0 and was stable at 50 C in the acid range. N-bromosuccinimide caused complete inhibition of lytic activity at 1 mM, whereas calcium and magnesium ions at the same concentration caused activation. Mutanolysin had lytic or bactericidal activity against the living cells of Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, Lactobacillus acidophilus, and Actinomyces viscosus, which are considered to be etiologic agents of dental caries, but had no activity against S. aureus and all gram-negative strains tested. The lytic activity was well retained in human saliva. Digestion of the cell walls of S. mutans BHT by mutanolysin was accompanied by the liberation of free amino groups and reducing sugars. Mutanolysin may be expected to be a useful agent for dental caries control.
Requirement for CD100–CD72 interactions in fine-tuning of B-cell antigen receptor signaling and homeostatic maintenance of the B-cell compartment (2005)

Co-receptors on the B-cell surface regulate B-cell antigen receptor (BCR) signaling; however, it remains unclear how BCR signals are coordinated to maintain immune homeostasis. CD72, a negative regulator of B-cell responses, has immunoreceptor tyrosine-based inhibitory motifs within its cytoplasmic region, and the tyrosine phosphatase SHP-1 binds these sites. The natural ligand of CD72, CD100/Sema4D, belongs to the semaphorin family and induces the dissociation of SHP-1 from CD72, thereby switching off the negative signals of CD72. In the absence of CD100, BCR signals are significantly suppressed due to the constitutive association of SHP-1 with CD72, resulting in B-cell hyporesponsiveness. Here we show that CD100 regulates the sensitivity of the BCR by preventing the association of the CD72 with BCR, and this interaction is required for proper B-cell homeostasis. Consequently, as CD100-deficient mice age, they accumulate marginal zone B cells and develop high auto-antibody levels and autoimmunity. Collectively, our findings indicate that the strength of BCR signals is strictly tuned by the interaction of CD100 with CD72, and this interaction is essential for maintaining immunological homeostasis as well as generating a proper immune response.