gebhart/patrepeval huggingface dataset:
MiR-34a inhibits oral cancer progression partially by repression of interleukin-6-receptor. (2015)

Previous reports revealed that a significant decrease of miR-34a in oral cancer. But the role of miR-34a in oral cancer needs further research. In the present study, we will investigate the effect of miR-34a on oral cancer cell phenotypes. First, it was verified that miR-34a expression was lower in oral cancer tissues compared with their normal controls, so did the oral cancer cells. Next, it was showed that miR-34a overexpression in oral cancer cells could inhibit cell proliferation, G1 phase arrest, metastasis and epithelial mesenchymal transition. It was predicted that interleukin-6-receptor (IL6R) was a potential target gene of miR-34a by bioinformatics analysis and identified by luciferase assay. It was further showed that miR-34a inhibited oral cancer progression via IL6R. Collectively, our findings suggested that miR-34a may function as a tumor suppressor in oral cancer by targeting IL6R.
Benzoxocin and benzoxonin derivatives. Novel groups of terpenophenols with central nervous system activity (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBenzoxocin and benzoxonin derivatives. Novel groups of terpenophenols with central nervous system activityShlomo Houry, Raphael Mechoulam, Philip J. Fowler, Edward Macko, and Bernard LoevCite this: J. Med. Chem. 1974, 17, 3, 287–293Publication Date (Print):March 1, 1974Publication History Published online1 May 2002Published inissue 1 March 1974https://pubs.acs.org/doi/10.1021/jm00249a006https://doi.org/10.1021/jm00249a006research-articleACS PublicationsRequest reuse permissionsArticle Views153Altmetric-Citations12LEARN 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
Dry Media Synthesis of Novel Pyrrolo-pyrimidines (1970)

A series of new 2-thioxo-3,7-disubstituted-5,6-diphenylpyrrolo[2,3-d]pyrimidin-4(1H)-ones have been synthesized by the condensation of 2-amino3-ethylcarboxylate-4,5-diphenylpyrroles with mono-substituted arylthioureas in dry media under microwave irradiations.All the synthesized compounds were screened for their antifungal and antibacterialactivities and found to possess mild to moderate antimicrobial activities.Keywords: Thioureas, Pyrrolo-pyrimidines, Microwave irradiation, Antimicrobial activities.DOI: 10.3126/jncs.v25i0.3306Journal of Nepal Chemical Society Volume 25, 2010 pp 83-88
Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen (1997)

The natural product rapamycin has been used to provide temporal and quantitative control of gene expression in animals through its ability to interact with two proteins simultaneously. A shortcoming of this approach is that rapamycin is an inhibitor of cell proliferation, the result of binding to FKBP12-rapamycin-associated protein (FRAP). To overcome this limitation, nontoxic derivatives of rapamycin bearing bulky substituents at its C16-position were synthesized, each in a single step. The isosteric isopropoxy and methallyl substituents with the nonnatural C16-configuration abolish both binding to FRAP and inhibition of T cell proliferation. Binding proteins for these derivatives were identified from libraries of cDNAs encoding mutants of the FKBP12-rapamycin-binding (FRB) domain of FRAP by using a mammalian three-hybrid transcription assay. Targeting of the mutations was guided by the structure of the FKBP12-rapamycin-FRB ternary complex. Three compensatory mutations in the FRB domain, all along one face of an alpha-helix in a rapamycin-binding pocket, were identified that together restore binding of the rapamycin derivatives. Using this mutant FRB domain, one of the nontoxic rapamycin derivatives induced targeted gene expression in Jurkat T cells with an EC50 below 10 nM. Another derivative was used to recruit a cytosolic protein to the plasma membrane, mimicking a process involved in many signaling pathways.
Mutated and non‐mutated TP53 as targets in the treatment of leukaemia (2008)

TP53 is mutated in 10-20% of cases of chronic lymphocytic leukaemia (CLL) and 3-8% of cases of acute myeloid leukaemia (AML). Recently, two classes of compounds that restore the function of p53 in tumours have been described. PRIMA-1 (p53-dependent reactivation and induction of massive apoptosis) restores the wild-type conformation of mutant TP53, whereas RITA (reactivation of p53 and induction of tumour cell apoptosis) increases intracellular levels of p53. We evaluated the effects of RITA alone and in combination with PRIMA-1 or conventional cytostatics on leukaemic cells isolated from AML and CLL patients. AML samples with -17, which are more resistant to daunorubicin and cytarabine compared with samples without -17, were effectively killed by PRIMA-1. RITA, which stabilizes the function of wild-type p53, induced apoptosis in AML cells. In contrast to that seen with PRIMA-1, AML patient samples without -17 were significantly more sensitive to RITA. Similarly, RITA exerted dose-dependent apoptosis and cytotoxicity in CLL cells, which was significantly more pronounced in samples without hemizygous TP53 deletion. Notably, a synergistic effect was observed in all CLL samples with RITA and fludarabine in combination. In both AML and CLL cells exposure to RITA resulted in induction of intracellular p53. We conclude that small molecules targeting p53 might be of clinical importance in the future for treating drug-resistant leukaemia.
Persistent Activation of Nuclear Factor–κB Signaling Pathway in Severe Uncontrolled Asthma (2003)

The transcription factor nuclear factor-kappaB (NF-kappaB) is inactive when bound to its inhibitory protein IkappaBalpha. On cell stimulation with inflammatory signals, IkappaBalpha is phosphorylated by IkappaB kinases and subsequently degraded. Freed NF-kappaB then induces expression of cytokines such as granulocyte-macrophage colony-stimulating factor, interleukin-8, and regulated upon activation, normal T cell expressed and secreted. These mediators are overexpressed in asthma and are downregulated by glucocorticoids through NF-kappaB activity repression. However, high levels of granulocyte-macrophage colony-stimulating factor, interleukin-8, and regulated upon activation, normal T cell expressed and presumably secreted are released by peripheral blood mononuclear cells isolated from patients with severe asthma despite continuous systemic glucocorticoid treatment. We report that these mediators are markedly decreased by pyrrolidinedithiocarbamate, an inhibitor of NF-kappaB activation. To further characterize the persistent NF-kappaB activation in severe asthma, we analyzed the expression of various components of this activation pathway in healthy subjects and in asthmatics with mild controlled, and moderate and severe uncontrolled disease. We found high amounts of phosphorylated IkappaBalpha characterizing the three asthmatic groups. Western blot analyses indicated that in peripheral blood mononuclear cells the IkappaB kinase beta and p65 levels were greater in moderate and severe asthmatics than in normal subjects. Electrophoretic mobility shift assay and immunocytochemistry showed a greater activation status of p65 in severe asthmatics. Our data suggest that exaggerated NF-kappaB activation perpetuates inflammatory mediators production in severe asthma.
Positional Therapy for Obstructive Sleep Apnea Patients: A 6‐Month Follow‐Up Study (2006)

Positional therapy appears to be a valuable form of therapy mainly for some older aged positional OSA patients.
Representation and learning of concepts based on scope (2002)

The authors assume that meanings of concepts consist of relations among concepts (definitions of concepts) and a habit which an agent using concepts has. They formulate this idea as a new framework of a knowledge representation system of concepts by introducing scope, i.e., a set of concepts which is in the present consideration. In the framework, they treat relations among concepts by means of partial extensions, i.e., functions from a possible model of subtheory, which is determined by the present scope, to the extension of each concept at the model. A habit is treated as a restriction of motion of scope. Then, inference based on the framework and a connection between efficiency of reasoning and a semantic property are studied. This connection leads to the possibility of extending explanation-based learning.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Zur Kenntnis der Organophosphorverbindungen, IV. Darstellung von Dialkylphosphorverbindungen (1962)

Abstract Die aus PSCl 3 mit n‐Alkylmagnesiumhalogeniden entstehenden Tetraalkyldiphosphindisulfide R 2 P(S)—P(S)R 2 sind ein bequem zugängliches Ausgangs‐material für die Synthese von Dialkylphosphorverbindungen. So wird z. B. die P—P‐Bindung dieser Stoffe durch Chlor oder Brom glatt gespalten. Hierbei entstehen Dialkylphosphorthiohalogenide R 2 P(S)X (X = Cl, Br), die mit weiterem Halogen Dialkylphosphortrichloride R 2 PCl 3 bzw. Verbindungen des Typs R 2 PBr 3 ·Br 2 liefern. Die physikalischen Eigenschaften sowie Leitfähigkeitsmessungen lassen auf eine ionische Struktur dieser Verbindungen, gemäß [R 2 PCl 2 ]⊕[R 2 PCl 4 ]⊖ bzw. [R 2 PBr 2 ]⊕Br 3 ⊖, schließen. Dialkylthiophosphonsäureester R 2 P(S)OR wurden bei der Reaktion von R 2 P(S)Br mit Alkoholen erhalten.
Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing (2004)

Complex recombinant antibody fragments for modulation of immune function such as tumor cell destruction have emerged at a rapid pace and diverse anticancer strategies are being developed to benefit patients. Despite improvements in molecule design and expression systems, the quantity and stability, e.g., of single-chain antibodies produced in cell culture, is often insufficient for treatment of human disease, and the costs of scale-up, labor, and fermentation facilities are prohibitive. The ability to yield mg/ml levels of recombinant antibodies and the scale-up flexibility make transgenic production in plants and livestock an attractive alternative to mammalian cell culture as a source of large quantities of biotherapeutics. Here, we report on the efficient production of a bispecific single-chain antibody in the serum of transgenic rabbits and a herd of nine cloned, transgenic cattle. The bispecific protein, designated r28M, is directed to a melanoma-associated proteoglycan and the human CD28 molecule on T cells. Purified from the serum of transgenic animals, the protein is stable and fully active in mediating target cell-restricted T cell stimulation and tumor cell killing.
Fluorous Biphase Chemistry (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorous Biphase ChemistryIstván T. HorváthView Author Information Corporate Research, Exxon Research and Engineering Company, Route 22 East, Annandale, New Jersey 08801 Cite this: Acc. Chem. Res. 1998, 31, 10, 641–650Publication Date (Web):August 8, 1998Publication History Received12 December 1997Published online8 August 1998Published inissue 1 October 1998https://pubs.acs.org/doi/10.1021/ar970342ihttps://doi.org/10.1021/ar970342iresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views2937Altmetric-Citations680LEARN 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:Catalysts,Chemical reactions,Hydrocarbons,Reagents,Solvents Get e-Alerts
Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo (2008)

Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here that the overexpression of Hec1 in an inducible mouse model results in mitotic checkpoint hyperactivation. As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy. These results underscore the role of chromosomal instability as a result of mitotic checkpoint hyperactivation in the initiation of tumorigenesis.
Prevention of Bleomycin-induced Lung Fibrosis by Aerosolization of Heparin or Urokinase in Rabbits (2003)

Bleomycin is a well known fibrogenic agent, provoking an initial adult respiratory distress syndrome-like injury with subsequent strong fibroproliferative response. Severe abnormalities of the alveolar surfactant system, which may be linked to the appearance of alveolar fibrin deposition, have been implicated in the pathogenetic sequence of events. Using a model of standardized aerosol delivery of 1.8 U bleomycin/kg body weight in rabbits, we investigated the influence of repetitive nebulization of heparin or urokinase-type plasminogen activator (u-PA) on the development of lung fibrosis. In an "early" (Days 2-12 postbleomycin) or "late" (Days 14-24 post-bleomycin) treatment protocol, approximately 3,500 U heparin or approximately 6,500 U u-PA was delivered to the bronchoalveolar space. Within four weeks, the bleomycin challenge provoked severe pulmonary fibrosis with reduction of lung compliance, marked increase in soluble collagen (bronchoalveolar lavage fluid) and hydroxyproline content (lung tissue), a typical reticular fibrosis pattern on high-resolution computed tomography, and typical histologic findings. Therapeutic intervention resulted in a far-reaching normalization of compliance, suppression of soluble collagen and hydroxyproline accumulation, and virtual abrogation of the computed tomography scan and histologic features of lung fibrosis, with most prominent effects seen in the early heparin and late u-PA administration. No bleeding complications occurred. These findings strongly support the concept that alveolar fibrin generation is an important event in the development of postbleomycin lung fibrosis. "Compartmentalized" anticoagulation and/or fibrinolysis via inhalational deposition of interventional agents in the alveolar compartment may thus offer a new therapeutic strategy for prevention of fibrosis.
Manipulating core–shell reactivities for processing nanoparticle sizes and shapes (2000)

This paper describes new findings of an investigation of thermally-activated core–shell reactivities of nanoparticles in solutions for processing size, shape and surface properties. Gold nanoparticles of ≈2 nm core sizes with thiolate monolayer encapsulation were chosen as a model system for the manipulation of reaction parameters, including annealing effect, core composition and shell structure. It is revealed that, upon an evolution of particle sizes, annealing treatment of the solution in the presence of encapsulating thiols can lead to the formation of highly monodispersed nanoparticles. New insights into shell desorption, core coalescence and shell re-encapsulation have been provided by dependencies of the evolution temperature on the capping thiolate chain length and the core alloy composition. Transmission electron microscopic, FTIR and UV-Visible techniques were used to characterize the morphological and chemical properties. The implication of the results for the development of abilities in chemical processing core–shell nanoparticles is discussed.
Evaluation of Intact Mass Spectrometry for the Quantitative Analysis of Protein Therapeutics (2012)

Implementation of modern analytical techniques, such as intact mass spectrometry, may allow for more detailed quality assessments of protein therapeutics. The complexity of the protein therapeutic manufacturing process as well as the sensitivity of these drugs to different storage conditions can lead to the presence of several undesired products, including truncations, degradation products, byproducts, and differentially modified protein variants that are difficult to detect by peptide mapping. Intact mass spectrometry can be used to identify the intact protein composition, inclusive of post-translational modifications (PTMs) but can also generate a chemical fingerprint of the different protein species present in a given sample. In this work, we systematically evaluated the influence of multiple charge states, multiple isotopes per charge state, and operating resolution on the suitability of intact mass spectrometry for quantitative analysis using insulin and somatotropin as model systems. Standard curves could be generated using absolute intensity data or using the relative ratio between the analyte and internal standard. These methods demonstrate the validity of quantitative intact mass spectrometry for the analysis of protein therapeutic drugs, thus providing a foundation for future comparative methods.
Feedback control of regulatory T cell homeostasis by dendritic cells in vivo (2009)

CD4(+)CD25(+)Foxp3(+) natural regulatory T cells (T reg cells) maintain self-tolerance and suppress autoimmune diseases such as type 1 diabetes and inflammatory bowel disease (IBD). In addition to their effects on T cells, T reg cells are essential for maintaining normal numbers of dendritic cells (DCs): when T reg cells are depleted, there is a compensatory Flt3-dependent increase in DCs. However, little is known about how T reg cell homeostasis is maintained in vivo. We demonstrate the existence of a feedback regulatory loop between DCs and T reg cells. We find that loss of DCs leads to a loss of T reg cells, and that the remaining T reg cells exhibit decreased Foxp3 expression. The DC-dependent loss in T reg cells leads to an increase in the number of T cells producing inflammatory cytokines, such as interferon gamma and interleukin 17. Conversely, increasing the number of DCs leads to increased T reg cell division and accumulation by a mechanism that requires major histocompatibility complex II expression on DCs. The increase in T reg cells induced by DC expansion is sufficient to prevent type 1 autoimmune diabetes and IBD, which suggests that interference with this feedback loop will create new opportunities for immune-based therapies.
The Human Low Affinity Immunoglobulin G Fc Receptor III-A and III-B Genes (1995)

The human Fc receptor with low affinity for IgG (Fc gamma RIII, CD16) is encoded by two nearly identical genes, Fc gamma RIII-A and Fc gamma RIII-B, resulting in tissue-specific expression of alternative membrane-anchored isoforms. The transmembrane CD16 receptor forms a heteromeric structure with the Fc epsilon RI (gamma) and/or CD3 (zeta) subunits on the surface of activated monocytes/macrophages, NK cells, and a subset of T cells. The expression of the glycosylphosphatidylinositol-anchored CD16 isoform encoded by the Fc gamma RIII-B gene is restricted to polymorphonuclear leukocytes and can be induced by Me2SO differentiation of HL60 cells. We have isolated and sequenced genomic clones of the human Fc gamma RIII-A and Fc gamma RIII-B genes, located their transcription initiation sites, identified a different organization of their 5' regions, and demonstrated four distinct classes of Fc gamma RIII-A transcripts (a1-a4) compared with a single class of Fc gamma RIII-Bb1 transcripts. Both CD16 promoters (positions -198 to -10) lack the classical "TATA" positioning consensus sequence but confer transcriptional activity when coupled to the human lysozyme enhancer. Both promoters also display different tissue-specific transcriptional activities reflecting the expected gene expression of Fc gamma RIII-A and Fc gamma RIII-B in NK cells versus polymorphonuclear leukocytes. Within the -198/-10 fragments, the sequences of the two CD16 genes have been identified to differ in 10 positions. It is suggested that these nucleotide differences might contribute to cell type-specific transcription of Fc gamma RIII genes.
OSP: a computer program for choosing PCR and DNA sequencing primers. (1991)

OSP (Oligonucleotide Selection Program) selects oligonucleotide primers for DNA sequencing and the polymerase chain reaction (PCR). The user can specify (or use default) constraints for primer and amplified product lengths, %(G+C), (absolute or relative) melting temperatures, and primer 3' nucleotides. To help minimize nonspecific priming and primer secondary structure, OSP screens candidate primer sequences, using user-specifiable cutoffs, against potential base-pairing with a variety of sequences present in the reaction, including the primer itself, the other primer (for PCR), the amplified product, and any other sequences desired (e.g., repetitive element sequences in genomic templates, vector sequence in cloned templates, or other primer pair sequences in multiplexed PCR reactions). Base-pairing involving the primer 3' end is considered separately from base-pairing involving internal sequences. Primers meeting all constraints are ranked by a "combined score," a user-definable weighted sum of any of the above parameters. OSP is being routinely and extensively used to select sequencing primers for the Caenorhabditis elegans genome sequencing project and human genomic PCR primer pairs for the Washington University Genome Center mapping project, with success rates exceeding 96% and 81%, respectively. It is available for research purposes from the authors, at no cost, in both text output and interactive graphics (X windows) versions.
IL-10 Deficiency Increases Renal Ischemia-Reperfusion Injury (2014)

These data reveal an important role for IL-10 in the improvement of renal IR injury, acting through suppression of inflammatory mediators, and that IL-10 would be a crucial target for the treatment of IR injury.