gebhart/patrepeval huggingface dataset:
Single-cell analysis of dihydroartemisinin–induced apoptosis through reactive oxygen species–mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques (2010)

Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA-induced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future.
The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling (2006)

We studied antitumor effects of receptor tyrosine kinase inhibitor sunitinib (formerly SU11248) against a variety of hematologic malignancies including the following leukemias: eosinophilic (EOL-1), acute myeloid (THP-1, U937, Kasumi-1), biphenotypic (MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, PALL-2), blast crisis of chronic myeloid (KU812, Kcl-22, K562), and adult T-cell (MT-1, MT-2, MT-4), as well as non-Hodgkin's lymphoma (KS-1, Dauji, Akata) and multiple myeloma (U266). Thymidine uptake studies showed that sunitinib was active against EOL-1, MV4-11, and Kasumi-1 cells, which possessed activating mutations of the PDGFRalpha, FLT-3, and c-KIT genes, respectively, with IC(50)s of <30 nmol/L. In addition, sunitinib inhibited the proliferation of freshly isolated leukemia cells from patients possessing mutations in FLT3 gene. Annexin V staining showed that sunitinib induced apoptosis of these cells. Sunitinib inhibited phosphorylation of FLT3 and PDGFRalpha in conjunction with blockade of mammalian target of rapamycin signaling in MV4-11 and EOL-1 cells, respectively. Interestingly, rapamycin analogue RAD001 enhanced the ability of sunitinib to inhibit the proliferation of leukemia cells and down-regulate levels of mammalian target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 in these cells. Taken together, sunitinib may be useful for treatment of individuals with leukemias possessing activation mutation of tyrosine kinase, and the combination of sunitinib and RAD001 represents a promising novel treatment strategy.
Perspective layered visualization of collaborative workspaces (1999)

Visual shared workspaces will be always staying on users' screens in the near future. Users will be moving frequently between their personal workspaces for personal and asynchronous work and shared workspaces for communication and synchronous cooperation. Also the system should supports users' everyday awareness of co-workers. For supporting such situation, this paper proposes a new technique to visualize workspaces as a set of layered virtual screens in three-dimensional space. In this way, groups' shared spaces are shown as background of users' personal spaces like as looking from a top personal layer down to a bottom public layer. In conventional groupware, user's workspace is divided into some shared spaces and a personal space to show all of them simultaneously, so the size of the personal space is very restricted. This layered perspective visualization alleviates this problem and also supports users' awareness by always showing shared spaces in background.
Essential Role of Nuclear Factor (NF)-κB–Inducing Kinase and Inhibitor of κb (Iκb) Kinase α in Nf-κb Activation through Lymphotoxin β Receptor, but Not through Tumor Necrosis Factor Receptor I (2001)

Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB (IkappaB) kinase (IKK) have been implicated as essential components for NF-kappaB activation in response to many external stimuli. However, the exact roles of NIK and IKKalpha in cytokine signaling still remain controversial. With the use of in vivo mouse models, rather than with enforced gene-expression systems, we have investigated the role of NIK and IKKalpha in signaling through the type I tumor necrosis factor (TNF) receptor (TNFR-I) and the lymphotoxin beta receptor (LTbetaR), a receptor essential for lymphoid organogenesis. TNF stimulation induced similar levels of phosphorylation and degradation of IkappaBalpha in embryonic fibroblasts from either wild-type or NIK-mutant mice. In contrast, LTbetaR stimulation induced NF-kappaB activation in wild-type mice, but the response was impaired in embryonic fibroblasts from NIK-mutant and IKKalpha-deficient mice. Consistent with the essential role of IKKalpha in LTbetaR signaling, we found that development of Peyer's patches was defective in IKKalpha-deficient mice. These results demonstrate that both NIK and IKKalpha are essential for the induction of NF-kappaB through LTbetaR, whereas the NIK-IKKalpha pathway is dispensable in TNFR-I signaling.
Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations (2011)

Although approximately 95% of patients with polycythemia vera (PV) harbor the V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the remaining patients. We conducted a European collaborative study to define the molecular and clinical features of patients harboring these mutations. Overall, 106 PVs were recruited and 17 different mutations identified. Irrespective of the mutation, two-thirds of patients had isolated erythrocytosis, whereas the remaining subjects had erythrocytosis plus leukocytosis and/or thrombocytosis. Compared with JAK2 (V617F)-positive PV patients, those with exon 12 mutations had significantly higher hemoglobin level and lower platelet and leukocyte counts at diagnosis but similar incidences of thrombosis, myelofibrosis, leukemia, and death. In a multivariable analysis, age more than 60 years and prior thrombosis predicted thrombosis. These findings suggest that, despite the phenotypical difference, the outcome of JAK2 exon 12 mutations-positive PV is similar to that of JAK2 (V617F)-positive PV.
Cloning and sequencing of human λ immunoglobulin genes by the polymerase chain reaction (1990)

Universal oligonucleotide primers, designed for amplifying and sequencing genes encoding the rearranged human lambda immunoglobulin variable region, were validated by amplification of the lambda light chain genes from four human heterohybridoma cell lines and in the generation of a cDNA library of human V lambda sequences from Epstein-Barr virus-transformed human peripheral blood lymphocytes. This technique allows rapid cloning and sequencing of human immunoglobulin genes, and has potential applications in the rescue of unstable human antibody-producing cell lines and in the production of human monoclonal antibodies.
An information system based on distributed objects (1987)

The Telesophy system is intended to provide transparent access to all of a community's online information. The scale of the system requires that it be distributed across many machines via a network; the multiple types and formats of the information require that it be a multimedia system. We describe a prototype that uses objects to represent, query, display, and edit information. A two-level storage system is used to store the objects on multiple servers; queries are processed by indexing servers layered on top of the storage system. New media types and new indexing schemes can be added simply by defining new classes within the existing framework.
Engineering, characterization and phage display of hepatitis C virus NS3 protease and NS4A cofactor peptide as a single-chain protein (1998)

The polyprotein encoded by hepatitis C virus (HCV) genomic RNA is processed into functional polypeptides by both host- and virus-encoded proteases. The HCV-encoded NS3 protease and its cofactor peptide NS4A form a non-covalent complex, which participates in processing the viral polyprotein. This proteolytic activity is believed to be essential for virus proliferation and thus the NS3 protease is a prime target for developing anti-HCV pharmacological agents. Recent X-ray crystallography structural studies have revealed the nature of this non-covalent complex between NS3 protease and the 'active' central segment of NS4A, providing the opportunity to design a single-chain polypeptide. To this end, the DNA sequence encoding for the NS4A peptide (residues 21-34) was genetically fused via a short linker, capable of making a beta-turn, to the N-terminus of the NS3 protease domain. This engineered single-chain NS3-protease (scNS3) is fully active with kinetic parameters virtually identical with those of the NS3/ NS4A non-covalent complex. Moreover, the scNS3 protease can be displayed on filamentous phage and affinity selected using an immobilized specific inhibitor. The scNS3 expressed as a soluble protein and in a phage-display format facilitates enzyme engineering for further structural studies and in vitro selection of potential drug-resistant mutants. These are important steps towards developing effective anti-protease compounds.
Novel Thiazole Based Heterocycles as Inhibitors of LFA-1/ICAM-1 Mediated Cell Adhesion (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel Thiazole Based Heterocycles as Inhibitors of LFA-1/ICAM-1 Mediated Cell AdhesionPauline J. Sanfilippo, Michele C. Jetter, Richard Cordova, Robert A. Noe, Erika Chourmouzis, Catherine Y. Lau, and Elizabeth WangCite this: J. Med. Chem. 1995, 38, 7, 1057–1059Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/jm00007a002https://doi.org/10.1021/jm00007a002research-articleACS PublicationsRequest reuse permissionsArticle Views264Altmetric-Citations23LEARN 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-AlertscloseSupporting Info (3)»Supporting Information Supporting Information Get e-Alerts
Mutants carrying conditionally lethal mutations in outer membrane genes omsA and firA (ssc) are phenotypically similar, and omsA is allelic to firA (1992)

We have previously identified the gene (the ssc gene) defective in the thermosensitive and antibiotic-supersusceptible outer membrane permeability mutant SS-C of Salmonella typhimurium and shown that this gene is analogous to the Escherichia coli gene firA (L. Hirvas, P. Koski, and M. Vaara, EMBO J. 10:1017-1023, 1991). Others have tentatively implicated firA in a different function, mRNA synthesis. Here we report that the defect in the thermosensitive outer membrane omsA mutant of E. coli (T. Tsuruoka, M. Ito, S. Tomioka, A. Hirata, and M. Matsuhashi, J. Bacteriol. 170:5229-5235, 1988) is due to a mutation in firA; this mutation changed codon 271 from serine to asparagine. The omsA-induced phenotype was completely reverted by plasmids containing wild-type firA or ssc. Plasmids carrying the omsA allele, or an identical mutant allele prepared by localized mutagenesis, under the control of lac elicited partial complementation. Transcomplementation studies with plasmids carrying various mutant alleles of the S. typhimurium gene indicated that the ability of these plasmids to complement the omsA mutation was similar to their ability to complement the ssc mutation. The antibiotic-supersusceptible phenotype of the omsA mutant closely resembled that of the ssc mutant, i.e., the omsA mutant was supersusceptible to hydrophobic antibiotics and large-peptide antibiotics against which the intact outer membrane is an effective permeability barrier. As previously demonstrated with the omsA mutant, the outer membrane of the ssc mutant became selectively ruptured after incubation for 1 h at the growth-nonpermitting temperature; 82% of the periplasmic beta-lactamase and less than 3% of the cytoplasmic marker enzyme were released into the medium. All of these findings are consistent with our concept that firA is an essential gene involved in generation of the outer membrane.
Expression of progastrin‐derived peptides and gastrin receptors in a panel of gastrointestinal carcinoma cell lines (1998)

To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin-derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine-extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio-immunoassay. Low-affinity binding sites for glycine-extended gastrin and amidated gastrin were present, but high-affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine-extended gastrin nor amidated gastrin in the concentration range 10pmol/L-10nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine-extended gastrins as extracellular autocrine growth factors.
Cinéma et catholicisme (2015)

notamment par photocopie, n'est autorise que dans les limites des conditions gnrales d'utilisation du site ou, le cas chant, des conditions gnrales de la licence souscrite par votre tablissement. Toute autre reproduction ou reprsentation, en tout ou partie, sous quelque forme et de quelque manire que ce soit, est interdite sauf accord pralable et crit de l'diteur, en dehors des cas prvus par la lgislation en vigueur en France. Il est prcis que son stockage dans une base de donnes est galement interdit.
Prenatal Association between a Chemosensory Cue (Cineole) and Ethanol Postabsortive Effects Modulates Later Operant Responsiveness to Cineole-Flavored Milk in 1 Day Old Rats (2011)

"Los fetos de rata a término detectan, y asocian ent re sí, las propiedades sensoriales y farmacológicas del etanol. En el pre sente estudio se evaluaron cambios en un aprendizaje operante, en fu nción de las experiencias fetales con etanol. Los tratamientos p renatales fueron: Grupo "Apareado", las hembras fueron administradas con ci neol y 15-min después con etanol (2.0 g/kg); Grupo "Larga-Huella", se adm inistró cineol y 6 horas mas tarde, etanol y Grupo "Agua", las hembras recib ieron dos administraciones de agua separadas por 15 minutos. Las crías fueron entrenadas en una tarea operante. Se emplearon dos condiciones de aprendizaje (apareado y acoplado). Los sujetos "Apa reados" fueron entrenados bajo un esquema de reforzamiento continu o. Los sujetos "Acoplados” recibieron el reforzador de manera independiente de su conducta. Los reforzadores fueron leche o leche saborizada con cineol. Los resultados sugieren que las memorias prenatales relacionadas al alcohol pueden modular las respuestas operantes cuando las crías son re-expuestas a claves predictoras de los efectos tóxicos etílicos."
Thrombospondin‐1 as an endogenous inhibitor of angiogenesis and tumor growth (2002)

Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that influences cellular phenotype and the structure of the extracellular matrix. These effects are important components of the tissue remodeling that is associated with angiogenesis and neoplasia. The genetic mutations in oncogenes and tumor suppressor genes that occur within tumor cells are frequently associated with decreased expression of TSP-1. However, the TSP-1 that is produced by stromal fibroblasts, endothelial cells and immune cells suppresses tumor progression. TSP-1 inhibits angiogenesis through direct effects on endothelial cell migration and survival and through indirect effects on growth factor mobilization. TSP-1 that is present in the tumor microenvironment also acts to suppress tumor cell growth through activation of transforming growth factor beta in those tumor cells that are responsive to TGF beta. In this review, the molecular basis for the role of TSP-1 in the inhibition of tumor growth and angiogenesis is summarized.
Pyrrolidines. VII. 3-Hydroxy-1-Pyrrolidinecarboxylic Acid Esters (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPyrrolidines. VII. 3-Hydroxy-1-Pyrrolidinecarboxylic Acid EstersYao-Hua. Wu, William A. Gould, Walter G. Lobeck, Herbert R. Roth, and R. F. FeldkampCite this: J. Med. Chem. 1962, 5, 4, 752–762Publication Date (Print):July 1, 1962Publication History Published online1 May 2002Published inissue 1 July 1962https://pubs.acs.org/doi/10.1021/jm01239a007https://doi.org/10.1021/jm01239a007research-articleACS PublicationsRequest reuse permissionsArticle Views234Altmetric-Citations22LEARN 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 options Get e-Alerts
Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats (2013)

The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions.
The <inline-formula><math display="inline" overflow="scroll"><msub><mi>k</mi><mrow><mn>3</mn></mrow></msub></math></inline-formula> coefficient in nonparaxial λ/NA scaling equations for resolution, depth of focus, and immersion lithography (2002)

The Rayleigh's equations for resolution and depth of focus(DOF) have been the two pillars of optical lithography, defining the dependency of resolution and DOF to wavelength and to the numerical aperture (NA) of the imaging system. Scaling of resolution and DOF as well as determination of k 1 and k 2 have been depending on these two equations. However, the equation for DOF is a paraxial approximation. Rigorously solving the optical path difference as a function of wavelength and NA produces a DOF depending on the inverse of the square of the numerical half aperture instead of the numerical full aperture. Using this new DOF scaling equation and a new coefficient of DOF k 3 , the previously determined DOF have been shown to be overestimated by 10%-20% at NA of 0.6 and 0.8, respectively. The equation for resolution does not suffer from paraxial approximation but both new equations remove an ambiguity when the refractive index in the imaging medium is larger than unity. Application to immersion lithography using these equations is included.
Individualized Still-Picture Communication on a Two-Way Broad-Band CATV System (1975)

The principle and the equipment developed for the field trial on individualized still-picture communication applicable to a two-way CATV system are explained. Individualized still-picture communication is realized by a oneframe time-division-multiplex technique which enables many subscribers to share a television transmission channel. This technique will largely increase the capability of conventional CATV systems. Two kinds of new services, i.e., still-picture information retrieval and still-picture two-way communication between subscribers, have been successfully tested with a model system located at the Suzuka Telecommunication Training School, Nippon Telegraph and TelePhone Public Corporation. Brief explanation is also given about still-picture information retrieval system using a polling method which is currently under development.