gebhart/patrepeval huggingface dataset:
An Acidic Motif within the Third Intracellular Loop of the .alpha.2C2 Adrenergic Receptor Is Required for Agonist-Promoted Phosphorylation and Desensitization (1995)

The alpha 2C2 adrenergic receptor contains a highly acidic stretch of amino acids (EDEAEEEEEEEEEEEE) within the third intracellular loop. To investigate the role of this region, we utilized site-directed mutagenesis to delete these 16 amino acids as well as to substitute them with glutamine, thereby conserving size but not charge. The wild-type and mutated alpha 2C2 receptors were permanently expressed in CHO cells. Neither substitution nor deletion of this region affected receptor expression, agonist or antagonist binding affinities, guanine nucleotide-sensitive formation of the high-affinity agonist-receptor-G protein complex, or functional coupling of the receptor to Gi. We considered that since alpha 2C2 agonist-promoted desensitization is due to phosphorylation by the beta-adrenergic receptor kinase (or a related kinase), that this region may be important for establishing the acidic mileau required by this kinase. Therefore, the consequences of 30 min of agonist preexposure on subsequent alpha 2C2-mediated inhibition of adenylyl cyclase and on high-affinity agonist binding were determined for the wild-type and these two mutants. The wild-type alpha 2C2 receptor underwent approximately 52% functional desensitization and a approximately 40% loss of high-affinity binding after such exposure. In contrast, deletion and substitution of this acidic stretch of amino acids ablated desensitization as assessed by both approaches. These results correlated with those obtained in whole cell phosphorylation experiments. Cells expressing each receptor were incubated with [32P]orthophosphate and exposed to agonist, and receptors were purified by immunoprecipitation. The deletion and the substitution mutant receptors underwent agonist-promoted phosphorylation at levels of only 44 +/- 5% and 50 +/- 15%, respectively, relative to wild-type alpha 2C2.(ABSTRACT TRUNCATED AT 250 WORDS)
Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein (2002)

Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.
The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein. (1991)

Stimulation of the T-cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including phospholipase C (PLC) gamma 1 and the TCR zeta chain. We describe here a 70-kDa tyrosine phosphoprotein (ZAP-70) that associates with zeta within 15 sec following TCR stimulation. The phosphorylation of ZAP-70 and its association with zeta is independent of the other TCR chains since stimulation of a functional CD8/zeta chimeric receptor in a TCR-negative T cell leads to coprecipitation of ZAP-70 with the chimeric protein. In a Jurkat cell expressing the TCR and the CD8/zeta chimeric protein, tyrosine phosphorylation and association of ZAP-70 occurs exclusively with the stimulated receptor complex. In addition, a tyrosine kinase that does not appear to be fyn associates with the cytoplasmic domain of zeta and phosphorylates zeta and ZAP-70 in vitro.
Control of Hepatitis C:  A Medicinal Chemistry Perspective (2004)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTControl of Hepatitis C: A Medicinal Chemistry PerspectiveChristopher P. Gordon and Paul A. KellerView Author Information Department of Chemistry, University of Wollongong, Wollongong 2522, Australia Cite this: J. Med. Chem. 2005, 48, 1, 1–20Publication Date (Web):December 9, 2004Publication History Received16 January 2004Published online9 December 2004Published inissue 1 January 2005https://pubs.acs.org/doi/10.1021/jm0400101https://doi.org/10.1021/jm0400101review-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views1796Altmetric-Citations103LEARN 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:Genetics,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients (2015)

NIH and Astellas.
Noncytolytic Clearance of Sindbis Virus Infection from Neurons by Gamma Interferon Is Dependent on Jak/Stat Signaling (2009)

The alphavirus Sindbis virus (SINV) causes encephalomyelitis in mice by infecting neurons of the brain and spinal cord. The outcome is age dependent. Young animals develop fatal disease, while older animals recover from infection. Recovery requires noncytolytic clearance of SINV from neurons, and gamma interferon (IFN-gamma) is an important contributor to clearance in vivo. IFN-gamma-dependent clearance has been studied using immortalized CSM14.1 rat neuronal cells that can be differentiated in vitro. Previous studies have shown that differentiated, but not undifferentiated, cells develop prolonged SINV replication and respond to IFN-gamma treatment with noncytolytic clearance of virus preceded by suppression of genomic viral RNA synthesis and reactivation of cellular protein synthesis. To determine the signaling mechanisms responsible for clearance, the responses of SINV-infected differentiated neurons to IFN-gamma were examined. IFN-gamma treatment of SINV-infected differentiated CSM14.1 cells, AP-7 olfactory neuronal cells, and primary dorsal root ganglia neurons triggered prolonged Stat-1 Tyr(701) phosphorylation, Stat-1 Ser(727) phosphorylation, and transient Stat-5 phosphorylation. Inhibition of Jak kinase activity with Jak inhibitor I completely reversed the neuroprotective and antiviral activities of IFN-gamma in differentiated cells. We conclude that activation of the Jak/Stat pathway is the primary mechanism for IFN-gamma-mediated clearance of SINV infection from mature neurons.
Differential requirements for cell-specific elastase I enhancer domains in transfected cells and transgenic mice. (1989)

The 134-bp enhancer region of the pancreatic elastase I gene is sufficient to direct pancreatic acinar cell-specific transcription in transgenic mice and in transfected cells in culture. Ten-base-pair scanner mutations in three separate enhancer domains that inactivate enhancer function in transfected pancreatic cells in culture have no significant effect in transgenic mice. Because any pair of the three domains is sufficient to direct pancreas-specific expression in mice, no one domain is required for pancreas-specific transcription. Disruption of any two domains does inactivate the enhancer function in transgenic mice. Therefore, the elastase I enhancer domains essential for function in transfected cells in culture are not essential in animals but have a redundant function not apparent in transfected cells. This redundant function is not because of the particular acinar cell line used for transfections, the nature of the reporter gene, or the state of integration of the foreign test gene. We conclude that a trans-acting transcription factor or a modification of a factor(s) present in pancreatic cells of an animal is absent in pancreatic acinar cell lines.
Low Threshold Optical Oscillations in a Whispering Gallery ModeCaF2Resonator (2004)

We have observed low-threshold optical hyperparametric oscillations in a high-Q fluorite whispering gallery mode resonator. The oscillations result from the resonantly enhanced four-wave mixing occurring due to Kerr nonlinearity of the material. We demonstrate that, because of the narrow bandwidth of the resonator modes as well as the high efficiency of the resonant frequency conversion, the oscillations produce stable narrow-band beat-note of the pump, signal, and idler waves. A theoretical model for this process is described.
Innovative Techniques For Two-Phase Flow Measurements (2008)

Two-phase flow is important in an increasing number of applications and industries. For example, the safety analysis codes for the nuclear energy industry require closure relations for the vapor-liquid interfacial transfer terms, while accurate two-phase pressure drop models are necessary to design the piping systems in the oil and gas industry. Also, two-phase flow occurs in heat exchangers, steam generators, chemical reactors, oil transportation and many other process equipments. In addition, development of accurate and suitable instrumentations for on-line monitoring and measurement of the solids concentration and velocity in gas-solid two-phase flows has proven to be a challenging problem with many scientists and engineers worldwide developing novel techniques for this application. This paper presents a review on the electrical-based measurement techniques for gas-solid and gas-liquid two-phase flows along with the most recent patents developed for two-phase flow measurements. Also, development of a novel method for the design of capacitance sensors for void fraction measurement and flow pattern identification was presented in detail. Keywords: void fraction, recent patents, capacitance sensor, novel design method, gas-liquid flow, gas-solid flow, Two-phase flow
Highly purified primitive hematopoietic stem cells are PML-RARA negative and generate nonclonal progenitors in acute promyelocytic leukemia (1995)

The hierarchical level of stem cell involvement in acute promyelocytic leukemia (APL) characterized by the pathognomonic PML-RARA fusion gene is unknown. To determine if the cells of the primitive hematopoietic stem cell compartment are involved in the leukemic process, we have used molecular and cell sorting techniques in peripheral blood and bone marrow (BM) cells at diagnosis from three patients with APL and t(15; 17). In two of them, clonality analysis was also possible using the BstXI polymorphic site of the PGK gene. The PML-RARA fusion gene was readily identified by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of BM cells obtained at diagnosis in all three patients. These same samples were then used to sort CD34+ cells and their CD38+ and CD38- subsets by fluorescence-activated cell sorting. In both female patients, CD34+/CD38+ and CD34+/CD38- cell fractions were polyclonal using PCR, whereas a monoclonal pattern was identified at the BM sample obtained at diagnosis either by Southern blotting or by PCR. Because of the high sensitivity of the PCR analysis, the polyclonal pattern of these cell populations could mask the presence of a minor clone. To detect this clone, we preformed RT-PCR analysis for t(15; 17). In one female patient, the abnormal PML-RAR fusion gene was found only in the more mature CD34+/CD38+ cell fraction using a nested PCR approach, whereas the polyclonal CD34+/CD38- fraction was PML-RARA negative. These findings were confirmed in a third patient with APL in whom the PML-RARA transcripts were absent in the CD34+/CD38- cell fraction. To study the clonality at the level of clonogenic progenitors, we used in one patient PGK analysis by PCR of individual burst-forming units-erythroid and colony-forming units-granulocyte-macrophage obtained from the CD34+/CD38- and CD34+/CD38+ cell populations at diagnosis and from the BM sample obtained during remission. The two highly purified cell populations gave rise to morphologically normal colonies clonal for both the BstXI site containing (A) and the BstXI site lacking (B) PGK allelles, indicating their polyclonal content, a pattern that was also found in clonogenic progenitors obtained at remission. These findings strongly suggest that the primitive hematopoietic stem cells as defined by the CD34+/CD38- antigens are not involved by the neoplastic process in APL. These results may have important implications for autografting strategies of retinoic acid/chemotherapy-resistant or relapsed patients.
On the representation of query term relations by soft Boolean operators (1985)

The language analysis component in most text retrieval systems is confined to a recognition of noun phrases of the type normally included in back-of-the-book indexes, and an identification of related terms included in a preconstructed thesaurus of quasi-synonyms. Even such a restricted language analysis is fraught with difficulties because of the well-known problems in the analysis of compound nominals, and the hazards and cost of constructing word synonym classes valid for large text samples.In this study an extended (soft) Boolean logic is used for the formulation of information retrieval queries which is capable of representing both the use of compound noun phrases as well as the inclusion of synonym constructions in the query statements. The operations of the extended Boolean logic are described, and evaluation output is included to demonstrate the effectiveness of the extended logic compared with that of ordinary text retrieval systems.
Evaluation of the Charge-Collection Efficiency of Dye-Sensitized Nanocrystalline TiO2 Solar Cells (1999)

Intensity modulated photovoltage spectroscopy (IMVS) and intensity modulated photocurrent spectroscopy (IMPS) are used to evaluate the charge-collection efficiency of dye-sensitized nanocrystalline TiO2 solar cells. The charge-collection efficiency of the photoinjected electrons from dye sensitization is estimated from the respective time constants for charge recombination at open circuit τoc and the combined processes of charge collection and charge recombination at short circuit τsc obtained by IMVS and IMPS measurements. Three models are developed for relating the charge-collection efficiency to τoc/τsc. The first model determines the charge-collection efficiency from τoc/τsc without considering the underlying physical processes measured by IMVS and IMPS. The second model obtains τoc/τsc by simulating the frequency response of IMVS and IMPS from the time-dependent continuity equation for simplified conditions. The third model determines the time constants for IMVS and IMPS from electron-concentration profiles calculated for constant light intensity and more realistic conditions. To obtain a realistic steady-state electron concentration profile, a nonlinear dependence of the rate of recombination on the electron concentration in the TiO2 film is considered. Furthermore, the continuity equation is modified to account for charge trapping and detrapping. For the first time, expressions are derived for calculating the time constants from the steady-state electron concentration profile. The validity of this method is demonstrated for the second model from which the exact IMPS and IMVS responses are calculated. The three models are compared with each other. A simple expression is derived for calculating the charge-collection efficiency from the measured values of τoc/τsc and the light intensity dependence of τoc.
Expression of Semliki Forest virus capsid protein from SV40 recombinant virus (1985)

Here, the proteolytic processing of the Semliki Forest virus (SFV) capsid protein was studied in the absence of other viral functions. Two different fragments of the SFV messenger cDNA, coding for capsid protein and 174 and 38 extra amino acids from the envelope proteins, respectively, were cloned in the late region of the SV40 viral DNA. Cells infected with the SV40 recombinant virus stocks were analyzed for the production of SFV capsid mRNA and polypeptide. Immunofluorescence staining of the infected cells indicated that the produced SFV capsid protein accumulated mainly in the nucleus. Polyacrylamide gel electrophoresis of the immunoprecipitated SFV capsid proteins showed that both recombinants yielded a labelled band equivalent in size to the SFV capsid protein. Thus the proteolytic processing takes place even under conditions where the capsid protein is the only virus-specified protein synthesized.
Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex (2012)

Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.
Transcriptional targeting of replication-defective adenovirus transgene expression to smooth muscle cells in vivo. (1997)

Gene transfer using replication-defective adenoviruses (RDAd) holds promise for the treatment of vascular proliferative disorders, but is potentially limited by the capacity of these viruses to infect multiple cell lineages. We have generated an RDAd vector, designated AdSM22-lacZ, which encodes the bacterial lacZ reporter gene under the transcriptional control of the smooth muscle cell (SMC)-specific SM22alpha promoter. Here, we show that in vitro AdSM22-lacZ programs expression of the lacZ reporter gene in primary rat aortic SMCs and immortalized A7r5 SMCs, but not in primary human umbilical vein endothelial cells (HUVECs) or NIH 3T3 cells. Consistent with these results, after intraarterial administration of AdSM22-lacZ to control and balloon-injured rat carotid arteries, beta-galactosidase activity was detected within SMCs of the tunica media and neointima, but not within endothelial or adventitial cells. Moreover, intravenous administration of AdSM22-lacZ did not result in lacZ gene expression in the liver or lungs. Finally, we have shown that direct injection of AdSM22-lacZ into SMC-containing tissues such as the ureter and bladder results in high-level transgene expression in visceral SMCs. Taken together, these results demonstrate that transgene expression after infection with an RDAd vector can be regulated in an SMC lineage-restricted fashion by using a transcriptional cassette containing the SMC-specific SM22alpha promoter. The demonstration of an efficient gene delivery system targeted specifically to SMCs provides a novel means to restrict expression of recombinant gene products to vascular or visceral SMCs in vivo.
Highly parallel SNP genotyping reveals high-resolution landscape of mono-allelic Ube3a expression associated with locus-wide antisense transcription (2010)

We investigated the allele- and strand-specific transcriptional landscape of a megabase-wide genomic region of mouse Ube3a (ubiquitin protein ligase E3A) by means of a highly parallel SNP genotyping platform. We have successfully identified maternal-specific expression of Ube3a and its antisense counterpart (Ube3a-ATS) in brain, but not in liver. Because of the use of inter-subspecies hybrid mice, this megabase-wide analysis provided high-resolution picture of the transcriptional patterns of this region. First, we showed that brain-specific maternal expression of Ube3a is restricted to the second half part of the locus, but is absent from the first half part. Balance of allelic expression is altered in the middle of the locus. Second, we showed that expression of the brain-specific Ube3a-ATS appeared to be terminated in the region upstream to the Ube3a transcription start site. The present study highlights the importance of locus-wide competition between sense and antisense transcripts.
Synthesis and pyrolytic behaviour of thiazolidin-2-one 1,1-dioxides (1997)

Four examples of the chiral thiazolidin-2-one 1,1-dioxides 5 have been prepared by reaction of the appropriate amino alcohols 11 with CS2 in aqueous sodium hydroxide to give the thiazolidine-2-thiones 12, followed by oxidation with KMnO4 under phase-transfer conditions in the presence of benzoic acid, either directly or via the thiazolidin-2-ones 13. Upon flash vacuum pyrolysis (FVP) at 650 °C, 5a–c decompose mainly by loss of SO2 to give an alkene and benzyl isocyanate together with other products from fragmentation of the N-benzyl group. A significant minor pathway involves net loss of CO2 and water to give the 2-phenyl-4,5-dihydrothiazoles 21 together with their aromatisation products 22 and 23. A mechanism for this new heterocyclic transformation is proposed involving initial expansion to a cyclic carbamic–sulfinic anhydride (2,1,4-oxathiazin-3-one 1-oxide). The fully assigned 13C NMR spectra are presented for 5, 12 and 13 and the 33S NMR spectrum has been obtained for 5c.
Chelation-Controlled Bergman Cyclization:  Synthesis and Reactivity of Enediynyl Ligands (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChelation-Controlled Bergman Cyclization: Synthesis and Reactivity of Enediynyl LigandsAmit Basak, Subrata Mandal, and Subhendu Sekhar BagView Author Information Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India Cite this: Chem. Rev. 2003, 103, 10, 4077–4094Publication Date (Web):September 13, 2003Publication History Received12 September 2002Published online13 September 2003Published inissue 1 October 2003https://doi.org/10.1021/cr020069kCopyright © 2003 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2869Altmetric-Citations173LEARN 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 Read OnlinePDF (686 KB) Get e-AlertsSUBJECTS:Cyclization,Ions,Ligands,Metals,Reactivity Get e-Alerts