gebhart/patrepeval huggingface dataset:
The role of ATP and adenosine in the brain under normoxic and ischemic conditions (2007)

By taking advantage of some recently synthesized compounds that are able to block ecto-ATPase activity, we demonstrated that adenosine triphosphate (ATP) in the hippocampus exerts an inhibitory action independent of its degradation to adenosine. In addition, tonic activation of P2 receptors contributes to the normally recorded excitatory neurotransmission. The role of P2 receptors becomes critical during ischemia when extracellular ATP concentrations increase. Under such conditions, P2 antagonism is protective. Although ATP exerts a detrimental role under ischemia, it also exerts a trophic role in terms of cell division and differentiation. We recently reported that ATP is spontaneously released from human mesenchymal stem cells (hMSCs) in culture. Moreover, it decreases hMSC proliferation rate at early stages of culture. Increased hMSC differentiation could account for an ATP-induced decrease in cell proliferation. ATP as a homeostatic regulator might exert a different effect on cell trophism according to the rate of its efflux and receptor expression during the cell life cycle. During ischemia, adenosine formed by intracellular ATP escapes from cells through the equilibrative transporter. The protective role of adenosine A(1) receptors during ischemia is well accepted. However, the use of selective A(1) agonists is hampered by unwanted peripheral effects, thus attention has been focused on A(2A) and A(3) receptors. The protective effects of A(2A) antagonists in brain ischemia may be largely due to reduced glutamate outflow from neurones and glial cells. Reduced activation of p38 mitogen-activated protein kinases that are involved in neuronal death through transcriptional mechanisms may also contribute to protection by A(2A) antagonism. Evidence that A(3) receptor antagonism may be protective after ischemia is also reported.
Localization of the high affinity calcium binding protein and an intrinsic glycoprotein in sarcoplasmic reticulum membranes. (1980)

Several proteins in sarcoplasmic reticulum preparations move in a band with a mobility, in sodium dodecyl sulfate-polyacrylamide gels (0.1 M phosphate buffer, pH 7.0), corresponding to a molecular mass of about 55,000 daltons. Only one of these proteins is the high affinity calcium binding protein. An intrinsic glycoprotein is also present in this band, and it is this glycoprotein which is found in vesicles reconstituted after dissolution of sarcoplasmic reticulum in deoxycholate. Both of these proteins are found in rather constant ratios with the ATPase in light, intermediate, and heavy sarcoplasmic reticulum vesicles. Transverse tubular vesicles can be isolated from the heavy sarcoplasmic reticulum vesicles after disruption of the membrane in a French pressure cell (Lau, Y.H., Caswell, A.H., and Brunschwig, J.P. (1977) J. Biol. Chem. 252, 5565-5574). These vesicles are enriched in their content of the high affinity calcium binding and depleted of the intrinsic glycoprotein. Cycloheptaamylose . fluorescamine complex (CFC) labels the intrinsic glycoprotein heavily indicating that it is at least partially exposed on the cytoplasmic surface of sarcoplasmic reticulum membranes. Since the carbohydrate component of the protein must lie in luminal spaces, it is inferred that the intrinsic glycoprotein is a transmembrane protein. The high affinity calcium binding protein is not labeled by CFC indicating that it is not exposed on the cytoplasmic surface of sarcotubular vesicles. The protein is also not affected by proteolytic digestion of sarcoplasmic reticulum vesicles and can be isolated intact from trypsin-digested vesicles. It is not removed from sarcoplasmic-reticulum vesicles by washing with buffers containing Chelex 100 or ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA). These data show that the high affinity calcium binding protein is localized in the interior of the sarcotubular system and suggest that it might be common to both sarcoplasmic reticulum and transverse tubular membranes.
Immunological and Virological Analyses of Rhesus Macaques Immunized with Chimpanzee Adenoviruses Expressing the Simian Immunodeficiency Virus Gag/Tat Fusion Protein and Challenged Intrarectally with Repeated Low Doses of SIVmac (2013)

Human adenovirus (AdHu)-based candidate AIDS vaccine can provide protection from simian immunodeficiency virus (SIV) transmission and disease progression. However, their potential use may be limited by widespread preexisting immunity to the vector. In contrast, preexisting immunity to chimpanzee adenoviruses (AdC) is relatively rare. In this study, we utilized two regimens of prime-boost immunizations with AdC serotype SAd-V23 (also called AdC6) and SAd-V24 (also called AdC7) expressing SIV Gag/Tat to test their immunogenicity and ability to protect rhesus macaques (RMs) from a repeated low-dose SIVmac239 challenge. Both AdC6 followed by AdC7 (AdC6/7) and AdC7 followed by AdC6 (AdC7/6) induced robust SIV Gag/Tat-specific T cell responses as measured by tetramer staining and functional assays. However, no significant protection from SIV transmission was observed in either AdC7/6- or AdC7/6-vaccinated RMs. Interestingly, in the RMs showing breakthrough infections, AdC7/6-SIV immunization was associated with a transient but significant (P = 0.035 at day 90 and P = 0.033 at day 120 postinfection) reduction in the setpoint viral load compared to unvaccinated controls. None of the measured immunological markers (i.e., number or functionality of SIV-specific CD8(+) and CD4(+) T cell responses and level of activated and/or CCR5(+) CD4(+) target cells) at the time of challenge correlated with protection from SIV transmission in the AdC-SIV-vaccinated RMs. The robust immunogenicity observed in all AdC-immunized RMs and the transient signal of protection from SIV replication exhibited by AdC7/6-vaccinated RMs even in the absence of any envelope immunogen suggest that AdC-based vectors may represent a promising platform for candidate AIDS vaccines.
The Memory Cytotoxic T-Lymphocyte (CTL) Response to Human Cytomegalovirus Infection Contains Individual Peptide-Specific CTL Clones That Have Undergone Extensive Expansion In Vivo (1999)

Human cytomegalovirus (HCMV)-specific CD8(+) cytotoxic T lymphocytes (CTL) appear to play an important role in the control of virus replication and in protection against HCMV-related disease. We have previously reported high frequencies of memory CTL precursors (CTLp) specific to the HCMV tegument protein pp65 in the peripheral blood of healthy virus carriers. In some individuals, the CTL response to this protein is focused on only a single epitope, whereas in other virus carriers CTL recognized multiple epitopes which we identified by using synthetic peptides. We have analyzed the clonal composition of the memory CTL response to four of these pp65 epitopes by sequencing the T-cell receptors (TCR) of multiple independently derived epitope-specific CTL clones, which were derived by formal single-cell cloning or from clonal CTL microcultures. In all cases, we have observed a high degree of clonal focusing: the majority of CTL clones specific to a defined pp65 peptide from any one virus carrier use only one or two different TCRs at the level of the nucleotide sequence. Among virus carriers who have the same major histocompatibility complex (MHC) class I allele, we observed that CTL from different donors that recognize the same peptide-MHC complex often used the same Vbeta segment, although other TCR gene segments and CDR3 length were not in general conserved. We have also examined the clonal composition of CTL specific to pp65 peptides in asymptomatic human immunodeficiency virus-infected individuals. We have observed a similarly focused peptide-specific CTL response. Thus, the large population of circulating HCMV peptide-specific memory CTLp in virus carriers in fact contains individual CTL clones that have undergone extensive clonal expansion in vivo.
Prevalence of Pasteurella haemolytica in transported calves. (1983)

In 2 different years, calves from individual farms were sampled by nasal swab for Pasteurella haemolytica at the farm, at an auction barn, and at a feedyard after they had been transported 1,600 km. Serum antibody titers were determined and P haemolytica isolates were serotyped. The frequencies of P haemolytica isolations were low at the farm, greater at the auction barn, and markedly high at the feedyard. Serotype 2 was the predominant isolate at the farm, and serotype 1 was the predominant isolate at the feedyard and from the pneumonic lungs of the calves that died of acute respiratory tract disease. There was a significant farm-to-farm variation in the percentages of calves that developed respiratory tract disease.
Metal Binding Specificity of the MntABC Permease ofNeisseria gonorrhoeaeand Its Influence on Bacterial Growth and Interaction with Cervical Epithelial Cells (2008)

mntABC from Neisseria gonorrhoeae encodes an ABC permease which includes a periplasmic divalent cation binding receptor protein of the cluster IX family, encoded by mntC. Analysis of an mntC mutant showed that growth of N. gonorrhoeae could be stimulated by addition of either manganese(II) or zinc(II) ions, suggesting that the MntABC system could transport both ions. In contrast, growth of the mntAB mutant in liquid culture was possible only when the medium was supplemented with an antioxidant such as mannitol, consistent with the view that ion transport via MntABC is essential for protection of N. gonorrhoeae against oxidative stress. Using recombinant MntC, we determined that MntC binds Zn(2+) and Mn(2+) with almost equal affinity (dissociation constant of approximately 0.1 microM). Competition assays with the metallochromic zinc indicator 4-(2-pyridylazo)resorcinol showed that MntC binds Mn(2+) and Zn(2+) at the same binding site. Analysis of the N. gonorrhoeae genome showed that MntC is the only Mn/Zn metal binding receptor protein cluster IX in this bacterium, in contrast to the situation in many other bacteria which have systems with dedicated Mn and Zn binding proteins as part of distinctive ABC cassette permeases. Both the mntC and mntAB mutants had reduced intracellular survival in a human cervical epithelial cell model and showed reduced ability to form a biofilm. These data suggest that the MntABC transporter is of importance for survival of Neisseria gonorrhoeae in the human host.
Transient Inhibition of ATM Kinase Is Sufficient to Enhance Cellular Sensitivity to Ionizing Radiation (2008)

In response to DNA damage, the ATM protein kinase activates signal transduction pathways essential for coordinating cell cycle progression with DNA repair. In the human disease ataxia-telangiectasia, mutation of the ATM gene results in multiple cellular defects, including enhanced sensitivity to ionizing radiation (IR). This phenotype highlights ATM as a potential target for novel inhibitors that could be used to enhance tumor cell sensitivity to radiotherapy. A targeted compound library was screened for potential inhibitors of the ATM kinase, and CP466722 was identified. The compound is nontoxic and does not inhibit phosphatidylinositol 3-kinase (PI3K) or PI3K-like protein kinase family members in cells. CP466722 inhibited cellular ATM-dependent phosphorylation events and disruption of ATM function resulted in characteristic cell cycle checkpoint defects. Inhibition of cellular ATM kinase activity was rapidly and completely reversed by removing CP466722. Interestingly, clonogenic survival assays showed that transient inhibition of ATM is sufficient to sensitize cells to IR and suggests that therapeutic radiosensitization may only require ATM inhibition for short periods of time. The ability of CP466722 to rapidly and reversibly regulate ATM activity provides a new tool to ask questions about ATM function that could not easily be addressed using genetic models or RNA interference technologies.
Angiotensin-1 Receptor Autoantibodies (2000)

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Entheses--the bony attachments of tendons and ligaments. (2001)

Most tendons and ligaments have fibrocartilaginous entheses where there are 4 zones of tissue at their bony attachments--dense fibrous connective tissue, uncalcified fibrocartilage, calcified fibrocartilage and bone. Such entheses leave smooth, circumscribed markings on dried bones. The uncalcified fibrocartilage dissipates the bending of collagen fibres away from the bone, ensures that a stretched tendon or ligament does not narrow too close to the bone and acts as a mini growth plate. The zone is thickest at entheses where a great deal of bending of the tendon/ligament accompanies joint movement. The calcified fibrocartilage anchors the tendon/ligament to the bone and enables it to withstand shear. Enthesis fibrocartilage may be accompanied by sesamoid and periosteal fibrocartilages that similarly protect the enthesis from wear and tear and dissipate stress. Nevertheless, each fibrocartilage can show distinctive pathological changes. A wide variety of ECM molecules has been reported in enthesis fibrocartilage, but it is best characterised by its content of type II collagen and aggrecan which account for its compression-tolerance properties.
In vivo effects of the 5‐HT6 antagonist SB‐271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5‐HT, glutamate and aspartate (2000)

Although the 5-HT(6) receptor subtype was identified some 5 years ago, very little is known about its function within the brain. Here we demonstrate, for the first time, the neurochemical effects of a selective 5-HT(6) receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5-HT(6) receptor antagonist SB-271046 by simultaneous measurement of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NA), glutamate and aspartate from the striatum and frontal cortex. SB-271046 did not alter basal levels of 5-HT, DA and NA in either brain region. Similarly, there was no change basal levels of either of the excitatory amino acids within the striatum. In contrast, administration of SB-271046 (10 mg kg(-1) s.c.) produced a significant (P<0.05), tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex, reaching maximum values of 375.4+/-82.3 and 215. 3+/-62.1% of preinjection values, respectively.
Non-A, Non-B Hepatitis Unrelated to the Hepatitis C Virus (Non-ABC) (1995)

The history of non-ABC hepatitis is a kaleidoscope of intriguing, but often conflicting and confounding data. Studies of transfusion-associated non-ABC hepatitis are less convincing than they originally seemed. Chimpanzee cross-challenge studies, once the bastion for the theory of multiple NANB hepatitis agents, now have an alternative explanation in the impaired immune response associated with HCV infection and the ability of this agent to reinfect individuals previously assumed to be immune. Nonetheless, there are so many cases of acute and chronic NANB hepatitis that cannot currently be attributed to HCV that it is hard to avoid the implication of at least one, and possibly more, non-ABC hepatitis agents. There are now some transmission studies in small primates to support this contention, though recent chimpanzee transmission studies have been disappointingly negative. As with the hepatitis C virus, the breakthrough in this disease will not come from classic serology or virology, but from molecular biology. Similar molecular approaches to those that elucidated HCV are in progress and are promising in preliminary experiments. It is anticipated that the pace of molecular biology is such that a great deal more will be known about non-ABC in a relatively brief time, and perhaps one or more non-ABC agents will prove to be real and clinically relevant.
Clinical Utility of Real-Time Compression Ultrasonography for Diagnostic Management of Patients with Recurrent Venous Thrombosis (1992)

In the diagnostic management of patients with clinically suspected recurrent deep-vein thrombosis (DVT), there are potential limitations to all available diagnostic techniques. Since venous abnormalities may persist for some time after an acute thrombosis, the usefulness of compression ultrasonography (US) for the detection of recurrent DVT may be jeopardized. We determined the rate of normalization of an abnormal compression US test of the popliteal and the common femoral veins in patients after a first episode of proximal DVT. In a cohort of 60 consecutive patients, the test result was normalized in only 29, 44, 54, and 60% of patients at 3, 6, 9, and 12 months, respectively. The investigation shows that for the detection of recurrent DVT of the leg, real-time compression US (using the single criterion of compression of the common femoral and popliteal vein) is of limited value. Future studies need to be performed, using more subtle interpretation of the compression US result, by quantifying the extent of residual thrombus, which may increase the usefulness of this test in patients with recurrent symptoms.
Molecular Basis for Cyclooxygenase Inhibition by the Non-steroidal Anti-inflammatory Drug Naproxen (2010)

Naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid) is a powerful non-selective non-steroidal anti-inflammatory drug that is extensively used as a prescription and over-the-counter medication. Naproxen exhibits gastrointestinal toxicity, but its cardiovascular toxicity may be reduced compared with other drugs in its class. Despite the fact that naproxen has been marketed for many years, the molecular basis of its interaction with cyclooxygenase (COX) enzymes is unknown. We performed a detailed study of naproxen-COX-2 interactions using site-directed mutagenesis, structure-activity analysis, and x-ray crystallography. The results indicate that each of the pendant groups of the naphthyl scaffold are essential for COX inhibition, and only minimal substitutions are tolerated. Mutation of Trp-387 to Phe significantly reduced inhibition by naproxen, a result that appears unique to this inhibitor. Substitution of S or CH(2) for the O atom of the p-methoxy group yielded analogs that were not affected by the W387F substitution and that exhibited increased COX-2 selectivity relative to naproxen. Crystallization and x-ray analysis yielded structures of COX-2 complexed to naproxen and its methylthio analog at 1.7 and 2.3 Å resolution, respectively. The combination of mutagenesis, structure analysis, and x-ray crystallography provided comprehensive information on the unique interactions responsible for naproxen binding to COX-2.
High level heterologous expression inE.coliusing the anaerobically-activatednirBpromoter (1991)

The anaerobically-regulated nirB promoter was used to express heterologous genes in Escherichia coli. Under anaerobic conditions the promoter was able to express tetanus toxin fragment C at approximately 20% total cell protein (tcp) and the Bordetella pertussis antigen pertactin at greater than 30% tcp. These levels are comparable to those obtained for the same products using the tac promoter. The nirB promoter is very well regulated, giving almost two orders of magnitude increase in fragment C on complete removal of oxygen. The use of this anaerobically-induced promoter in the production of recombinant proteins in E. coli is discussed.
한,일 간 왜곡된 상호인식과 분쟁의 연동성에 대한 고찰 (2013)

한·일 관계는 그 역사가 오래된 만큼 그 안에 내포된 상호에 대한 감정이나 이미지가 다양하며 때로는 공존 공생하는 이웃으로 때로는 침략자의 얼굴로서 시대에 따라 그 이미지를 바꾸어 가며 지금까지도 그 관계성을 유지하고 있다. 그러나 이러한 관계성 안에서 지금의 한·일 관계에 큰 영향을 미치고 있는 것은 전쟁이나 침략의 기억들이며 이러한 기억의 잔상으로부터 파생된 상호에 대한 부정적 인식은 우호적 한·일 관계를 가로막는 커다란 방해물이 되고 있다. 본 논문에서는 이러한 한·일 간의 부정적 상호인식에 주목하고 선행연구로서 시게무라 (重村)·이이무라(飯村)의 한·일식 오리엔탈리즘에 주목하고 이 이론을 바탕으로 실제의 한·일 역사를 검토해 보는 것으로 한·일 관계에 있어 긴 시간동안 존속되어왔던 왜곡된 상호인식의 원류를 찾는 것을 그 목적으로 하고 있다. 그간 한·일 간의 부정적 상호 인식 및 불편한 관계성에 대해서는 중세, 근세에 일어난 전쟁이나 침략의 기억에서 파생된 피해의식 그리고 지배자의 우월 의식에서 그 원인을 찾으려하는 연구가 많았으나, 한·일 역사에서 나타나는 상호에 대한 부정적 인식의 기록은 이러한 예상을 훨씬 뛰어넘는 것으로 고대의 한·일 관계에서조차 확인된다. 고대 왕권 강화를 위한 전설의 창작 그리고 이러한 지배이데올로기의 구축과정에서 부수 적으로 발생된 상호에 대한 왜곡된 의식이 한·일 간의 부정적 상호인식의 시발점이라고 생각되며 이러한 왜곡된 상호 인식은 천황으로부터 지배 권력을 빼앗은 무가(武家)권력에 의해 사용되어 국내의 지배권의 강화 및 조선 침략의 대의명분으로서 이용되어 왔다. 힘에 의해 권력을 쟁취한 무가 권력으로서는 지배 정통성의 확보가 시급한 과제였으며 권력 기반 및 지배권이 불안정한 정권이 집권할 경우 천황의 권위에 대한 의존은 가속화되었다. 이러한 천황권위의 의존이야말로 일본의 왜곡된 한국 인식과 한국인에 대한 차별의식을 재생산시키는 촉매제 역할을 했으며 지배권력이 취약한 정권이 들어 설 때마다 예외없이 한·일 간에는 불행한 역사가 반복되었다. 현재, 한·일 관계는 어느 시대보다도 친밀한 관계를 유지하고 있으며 좋은 이웃으로서 공존번영하고 있다. 그러나 천황제도의 유지 및 천황을 중심으로 한 일본식 세계관의 존속, 그리고 이를 지배에 이용하려는 정치 권력의 존재는 한·일 관계에 있어서 커다란 불안 요소이며 언젠가 국내 지배의 이유로 천황권위에 대한 의존이 가속화 될 경우 과거의 불행한 역사가 반복될 가능성 또한 배제하지 못할 상황이다. 본 논문에서는 이러한 내용을 중심으로 한·일 역사를 검토하며 한·일 간에 있었던 전쟁이나 대립상황을 분석하는 것으로서 부정적 상호 인식의 역사적 전개 과정을 검토해본다.
Structure of the antibiotic OA-7653 (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of the antibiotic OA-7653Peter W. Jeffs, Benjamin Yellin, Luciano Mueller, and Sarah L. HealdCite this: J. Org. Chem. 1988, 53, 3, 471–477Publication Date (Print):February 1, 1988Publication History Published online1 May 2002Published inissue 1 February 1988https://pubs.acs.org/doi/10.1021/jo00238a002https://doi.org/10.1021/jo00238a002research-articleACS PublicationsRequest reuse permissionsArticle Views338Altmetric-Citations15LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts