gebhart/patrepeval huggingface dataset:
Concurrent updates with RCU (2014)

Read copy update (RCU) is a novel synchronization mechanism, in which the burden of synchronization falls completely on the updaters, by having them wait for all pre-existing readers to finish their read-side critical section. This paper presents citrus, a concurrent binary search tree (BST) with a wait-free Contains operation, using RCU synchronization and fine-grained locking for synchronization among updaters. This is the first RCU-based data structure that allows concurrent updaters. While there are methodologies for using RCU to coordinate between readers and updaters, they do not address the issue of coordination among updaters, and indeed, all existing RCU-based data structures rely on coarse-grained synchronization between updaters.
Therapeutic anti‐tumor immunity triggered by injections of immunostimulating single‐stranded RNA (2006)

Stabilized synthetic RNA oligonucleotides (ORN) and protected messenger RNA (mRNA) were recently discovered to possess an immunostimulatory capacity through their recognition by TLR 7 and 8. We wanted to find out whether this danger signal is capable of triggering anti-tumor immunity when injected locally into an established tumor. Using the mouse glioma tumor cell line SMA-560 in syngenic VM/Dk mice, we were able to show that intra-tumor injections of protamine-stabilized mRNA do indeed induce tumor regression and long-term anti-tumor immunity. Residual RNA-injected tumors show CD8 infiltration. Distant injections of protamine-protected mRNA and intra-tumor injection of naked mRNA also result in anti-tumor immunity. Although they are strong danger signals, RNA are labile molecules with a short half-life: they do not trigger side effects such as long-term, uncontrolled immunostimulation evidenced by splenomegaly in CpG DNA-treated mice. In conclusion, RNA molecules are potent and safe danger signals that are relevant for active immunotherapy strategies aimed at the eradication of solid tumors.
Whiskers. 4. Copolyesters of 4-hydroxybenzoic acid and 2-(4'-hydroxyphenyl)benzoxazole-5-carboxylic acid (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWhiskers. 4. Copolyesters of 4-hydroxybenzoic acid and 2-(4'-hydroxyphenyl)benzoxazole-5-carboxylic acidHans R. Kricheldorf and Sven A. ThomsenCite this: Macromolecules 1993, 26, 24, 6628–6632Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/ma00076a049https://doi.org/10.1021/ma00076a049research-articleACS PublicationsRequest reuse permissionsArticle Views96Altmetric-Citations5LEARN 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
The discovery of protein phosphatases: From chaos and confusion to an understanding of their role in cell regulation and human disease (1994)

TEST 02 - Elsevier's Scopus, the largest abstract and citation database of peer-reviewed literature. Search and access research from the science, technology, medicine, social sciences and arts and humanities fields.
Thimet oligopeptidase specificity: evidence of preferential cleavage near the C-terminus and product inhibition from kinetic analysis of peptide hydrolysis (1995)

The substrate-size specificity of human thimet oligopeptidase (EC 3.4.24.15) was investigated with oligomers of glycyl-prolyl-leucine (GPL)n where n = 2, 3, 4 and 5. These peptides were cleaved only at Leu-Gly bonds to give GPL as the single final product. Hydrolysis was most rapid with (GPL)3 and slowest with (GPL)5. The more water-soluble oligomers of Gly-Hyp-Leu showed the same trend. (Gly-Hyp-Leu)6 was not hydrolysed, consistent with the previous finding that substrates larger than 17 amino acids are not cleaved by thimet oligopeptidase. The cleavage of (GPL)3 to GPL fitted a sequential first-order model. First-order kinetics were unexpected as the initial substrate concentration was greater than Km. The anomaly was also seen during the cleavage of bradykinin and neurotensin, and in these cases first-order behaviour was due to potent competitive inhibition by the C-terminal product. The sequential mechanism for (GPL)3 breakdown by thimet oligopeptidase does not discriminate between initial cleavages towards the N- or C-terminus. As isoleucine is an unfavourable residue in P1, substrates were made in which selected leucine residues were replaced by isoleucine. GPL--GPI--GPL (where--represents the bond between the tripeptide units) was resistant to hydrolysis and GPI--GPL--GPL was cleaved only at the -Leu-Gly- bond. Experiments with isoleucine-containing analogues of (Gly-Hyp-Leu)4 showed that thimet oligopeptidase preferred to cleave these peptides near the C-terminus.
Hepatic Failure in a Patient Taking Rosiglitazone (2000)

Rosiglitazone may be associated with hepatic failure.
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies (2010)

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.
Parathyroid Hormone (PTH)-Related Protein Is a Potent Stimulator of Osteoclast-Like Multinucleated Cell Formation to the Same Extent as PTH in Mouse Marrow Cultures* (1989)

Induction of osteoclast-like multinucleated cells (MNCs) by various fragments of PTH-related protein (PTHrP) was examined in mouse marrow cultures. Osteoclast-like MNCs were defined as tartrate-resistant acid phosphatase (TRACP)-positive MNCs with calcitonin receptors. In all experimental protocols examined, PTHrP-(1-34) induced TRACP-positive MNCs at almost the same rate as PTH-(1-34). PTHrP-(1-29) was less potent than PTHrP-(1-34). PTHrP-(1-25) and PTHrP-(1-14) had no effect. PTHrP-(1-34) was more potent than PTH-(1-34) in increasing the accumulation of cAMP, but the former appeared to lose its activity more rapidly than the latter. Isobutylmethylxanthine increased the effect of PTHrP-(1-34) and PTH-(1-34) in inducing TRACP-positive MNCs. Furthermore, the calcium ionophore A23187 significantly increased the formation of TRACP-positive MNCs. The effect of PTH-(1-34) and PTHrP-(1-34) in inducing TRACP-positive MNCs was potentiated by adding A23187 but suppressed by adding verapamil simultaneously. The inhibition by verapamil was overcome by adding A23187. [Nle8,18,Tyr34]PTH-(3-34)amide inhibited the effect of not only PTH-(1-34) but also PTHrP-(1-34) in inducing both the accumulation of cAMP and the TRACP-positive MNC formation. These results show that PTHrP is a potent stimulator of osteoclast-like MNC formation to almost the same extent as PTH. It increases the number of osteoclast-like MNCs by a mechanism involving cAMP and calcium ions, and is most likely mediated through the same receptor. The controversial results of the bone-resorbing activity of PTH and PTHrP reported so far may be explained by the differences in the relative potencies of the respective hormones in increasing the intracellular cAMP and calcium ions and by the shorter half-life of PTHrP in culture medium.
Sublingual spray: a new technology oriented formulation with multiple benefits (2019)

Sublingual drug delivery system was a well-established platform for delivering the drug that need to exhibit quick action without any first-pass metabolic effect, but various pitfall in the regular sublingual drug delivery systems such as a tablet, capsule etc., that can be overcome by novel sublingual drug delivery technology such as particulate sublingual spray. Sublingual spray for drug administration has gained attention in the market since it proved its propensity to by-pass the first-pass metabolism and to initiate a rapid onset of action due to its atomized micro particulate nature, which is significantly higher than the other sublingual formulations. The approval of sublingual spray by the regulatory agencies may commence further research in this field by subsuming various essential drugs for indications such as cancer pain, cardiovascular issue etc. This article comprises a detailed study on the drawback of conventional sublingual drug delivery system and the approach by which these drawbacks can be overruled by spray technology in the sublingual area and the, in-depth mechanism of drug delivery through sublingual with the help of atomization followed by the entire formulation strategy along with evaluation and industrial perspective of the sublingual spray dosage form as a future tool of patient-friendly drug delivery.
Rapid cloning, expression, and functional characterization of paired αβ and γδ T-cell receptor chains from single-cell analysis (2016)

Transgenic expression of antigen-specific T-cell receptor (TCR) genes is a promising approach for immunotherapy against infectious diseases and cancers. A key to the efficient application of this approach is the rapid and specific isolation and cloning of TCRs. Current methods are often labor-intensive, nonspecific, and/or relatively slow. Here, we describe an efficient system for antigen-specific αβTCR cloning and CDR3 substitution. We demonstrate the capability of cloning influenza-specific TCRs within 10 days using single-cell polymerase chain reaction (PCR) and Gibson Assembly techniques. This process can be accelerated to 5 days by generating receptor libraries, requiring only the exchange of the antigen-specific CDR3 region into an existing backbone. We describe the construction of this library for human γδ TCRs and report the cloning and expression of a TRGV9/TRDV2 receptor that is activated by zoledronic acid. The functional activity of these αβ and γδ TCRs can be characterized in a novel reporter cell line (Nur77-GFP Jurkat 76 TCRα(-)β(-)) for screening of TCR specificity and avidity. In summary, we provide a rapid method for the cloning, expression, and functional characterization of human and mouse TCRs that can assist in the development of TCR-mediated therapeutics.
Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation (2004)

Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. DPPIV removes dipeptides from the N terminus of substrates, including many chemokines, neuropeptides, and peptide hormones. Specific inhibition of DPPIV is being investigated in human trials for the treatment of type II diabetes. To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). The crystal structure of the free form of the enzyme reveals two potential channels through which substrates could access the active site-a so-called propeller opening, and side opening. The crystal structure of the DPPIV/tNPY complex suggests that bioactive peptides utilize the side opening unique to DPPIV to access the active site. Other structural features in the active site such as the presence of a Glu motif, a well-defined hydrophobic S1 subsite, and minimal long-range interactions explain the substrate recognition and binding properties of DPPIV. Moreover, in the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a tetrahedral intermediate that occurs during catalysis. Conformational changes of S630 and H740 between DPPIV in its free form and in complex with tNPY were observed and contribute to the stabilization of the tetrahedral intermediate. Our results facilitate the design of potent, selective small molecule inhibitors of DPPIV that may yield compounds for the development of novel drugs to treat type II diabetes.
Regulation of the nisin operons in Lactococcus lactis N8 (1996)

The antibiotic peptide nisin produced by Lactococcus lactis is used as a food preservative due to its activity against spores and vegetative cells of Gram‐positive bacteria. The post‐translational maturation of this secreted peptide includes dehydration of serine and threonine residues, lanthionine formation and a proteolytic processing of 23 amino acids from the N‐terminus. Mutations in the nisZ, nisB and nisP genes of the biosynthetic nisZBTCIPRK nisin operon were made by gene replacement or integration of a plasmid. The mutations caused a drastic decrease of the transcription from the promoters upstream of the nisZBTCIPRK and nisFEG operons resulting in loss of nisin production and nisin immunity. The transcription of the nisin operons and nisin immunity could be partially restored by adding nisin to the growth medium of the cells. Nisin induction of the mutant strains also increased the level of the putative immunity NisI protein. These results showed that the nisZBTCIPRK operon is positively autoregulated and that the nisFEG operon is in the same regulon.
C-5 substituted pyrimidine nucleosides. 2. Synthesis via olefin coupling to organopalladium intermediates derived from uridine and 2'-deoxyuridine (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTC-5 substituted pyrimidine nucleosides. 2. Synthesis via olefin coupling to organopalladium intermediates derived from uridine and 2'-deoxyuridineDonald E. Bergstrom and Mark K. OgawaCite this: J. Am. Chem. Soc. 1978, 100, 26, 8106–8112Publication Date (Print):December 1, 1978Publication History Published online1 May 2002Published inissue 1 December 1978https://doi.org/10.1021/ja00494a014Request reuse permissionsArticle Views442Altmetric-Citations94LEARN 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 (988 KB) Get e-Alertsclose Get e-Alerts
[Prevention of contamination with a heat-and-moisture-exchanger (HME) and bacterial filter during clinical anesthesia]. (1998)

Although the use of HME and bacterial filter is a common practice to protect the anesthesia machine as well as the patients from bacterial contaminants, there is no report demonstrating the effectiveness of this filter in clinical anesthesia setting. We evaluated the actual effectiveness of the filter during clinical use. While the anesthesia breathing circuit, two bacterial filters (BB 50 T, Nihon PALL) and anesthesia bag, which were sterilized with ethylen oxide gas (EOG), were connected to the anesthesia machine and used continuously for one week, EOG sterilized HME and bacterial filter (BB 25 A, Nihon PALL) were changed before each anesthesia. Culture samples were taken from the BB 25 A, the breathing circuit and the machine side of the BB 50 T. Of the 117 BB 25 A samples taken, 6 were positive for Micrococcus, alpha-Streptococcus, Bacillus, and Staphylococcus epidermidis. From 21 breathing circuit "internal" samples, one was positive for Bacillus, Staphylococcus epidermidis. But the contamination from outside sources was suspected, since all the BB 25 as used with this circuit were negative. Use of BB 25 A prevents contamination of the breathing circuit for a period of one week. If we use BB 25 A in every anesthesia case, the changing of the breathing circuit is unnecessary, reducing the cost and simplifying procedures during clinical practice.
A Novel CD19-directed Recombinant Bispecific Antibody Derivative With Enhanced Immune Effector Functions for Human Leukemic Cells (2008)

A novel bispecific antibody-derived recombinant protein targeting leukemias and lymphomas was designed, a single-chain Fv triple body (sctb) consisting of 1 polypeptide chain with 3 scFvs connected in tandem. The distal scFvs were specific for the tumor antigen CD19, and the central scFv for the trigger molecule CD16 (FcgammaRIII) on natural killer (NK) cells and macrophages. We had previously built a disulphide stabilized (ds) bsscFv [19 x 16] with monovalent binding for CD19 from ds components. The sctb ds[19 x 16 x 19] also used ds components and displayed 3-fold greater avidity for CD19 than the bsscFv (KD = 13 vs. 42 nM), whereas both had equal affinity for CD16 (KD = 58 nM). Plasma half-lives in mice were 4 and 2 hours for the sctb and the bsscFv, respectively. In antibody-dependent cellular cytotoxicity reactions with human mononuclear cells as effectors, the sctb promoted equal lysis of leukemic cell lines and primary cells from leukemia and lymphoma patients at 10-fold to 40-fold lower concentrations than the bsscFv. This new format may also be applicable to a variety of other tumor antigens and effector molecules. With half-maximum effective concentrations (EC50) in the low picomolar range, the sctb ds[19 x 16 x 19] is an attractive candidate for further preclinical evaluation.
An intelligent test sheet composition system (2008)

Computer-based tests have been proven to be more effective and efficient than traditional paper-and-pencil tests, so more and more examinations begin to offer computerized form, taking the Professional Qualification Examination for example. In this paper, according to the item bank and composition rules in the Professional Qualification Examination, we propose an intelligent test sheet composition system to generate the test sheet automatically. The test sheets composed by this system can not only meet the composition rules but also be different even if the same rule.
The Ratios of CD8+ T Cells to CD4+CD25+ FOXP3+ and FOXP3- T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer (2013)

Ovarian cancer is an immune reactive malignancy with a complex immune suppressive network that blunts successful immune eradication. This suppressive microenvironment may be mediated by recruitment or induction of CD4(+) regulatory T cells (Tregs). Our study sought to investigate the association of tumor-infiltrating CD4(+)CD25(+)FOXP3(+) Tregs, and other immune factors, with clinical outcome in serous ovarian cancer patients. We performed immunofluorescence and quantification of intraepithelial tumor-infiltrating triple positive Tregs (CD4(+)CD25(+)FOXP3(+)), as well as CD4(+)CD25(+)FOXP3(-), CD3(+) and CD8(+) T cells in tumor specimens from 52 patients with high stage serous ovarian carcinoma. Thirty-one of the patients had good survival (i.e. > 60 months) and 21 had poor survival of < 18 months. Total cell counts as well as cell ratios were compared among these two outcome groups. The total numbers of CD4(+)CD25(+)FOXP3(+) Tregs, CD4(+)CD25(+)FOXP3(-), CD3(+) and CD8(+) cells were not significantly different between the groups. However, higher ratios of CD8(+)/CD4(+)CD25(+)FOXP3(+) Treg, CD8(+)/CD4(+) and CD8/CD4(+)CD25(+)FOXP3(-) cells were seen in the good outcome group when compared to the patients with poor outcome. These data show for the first time that the ratios of CD8(+) to both CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) T cells are associated with disease outcome in ovarian cancer. The association being apparent in ratios rather than absolute count of T cells suggests that the effector/suppressor ratio may be a more important indicator of outcome than individual cell count. Thus, immunotherapy strategies that modify the ratio of CD4(+)CD25(+)FOXP3(+) Tregs or CD4(+)CD25(+)FOXP3(-) T cells to CD8(+) effector cells may be useful in improving outcomes in ovarian cancer.
Glucocorticoid‐induced leucine zipper (GILZ): a new important mediator of glucocorticoid action (2009)

Glucocorticoids (GCs) represent the mainstay of current anti-inflammatory and immunosuppressive strategies, mediating effects that mostly result in transcriptional regulation of glucocorticoid receptor target genes. A variety of actions are tied together in the response to GC treatment. Dissecting the beneficial from the detrimental actions in GC therapy is a major challenge in basic research, raising the critical issue of whether a single target gene or gene family might eventually be linked to a specific GC function. Glucocorticoid-induced leucine zipper (GILZ) was originally discovered in studies aimed at characterizing genes targeted by dexamethasone. The first suggestion that GILZ plays an important role in GC immunomodulation came from observations of GILZ up-regulation by GCs, mainly in lymphoid organs, and inhibition of anti-CD3-induced activation and apoptosis. The identification of GILZ interaction with and inhibition of NF-kappaB provided a first molecular mechanistic basis for explaining GILZ effects on T cells. Subsequently, other GILZ targets have been identified, including AP-1, Raf-1, and Ras, all involved in GC effects. The finding that GILZ silencing abrogates the antiproliferative activity of dexamethasone and reduces GC inhibition of cytokine-induced COX-2 expression clearly gained GILZ a distinguished reputation within the critical mediators of GC effects. The multiple functions of GILZ and their potential biological relevance are here reviewed.