gebhart/patrepeval huggingface dataset:
Effects of Learning on Smooth Pursuit During Transient Disappearance of a Visual Target (2003)

Previous research has demonstrated learning in the pursuit system, but it is unclear whether these effects are the result of changes in visual or motor processing. The ability to maintain smooth pursuit during the transient disappearance of a visual target provides a way to assess pursuit properties in the absence of visual inputs. To study the long-term effects of learning on nonvisual signals for pursuit, we used an operant conditioning procedure. By providing a reinforcing auditory stimulus during periods of accurate tracking, we increased the pursuit velocity gain during target blanking from 0.59 in the baseline session to 0.89 after 8 to 10 daily sessions of training. Learning also reduced the occurrence of saccades. The learned effects generalized to untrained target velocities and persisted in the presence of a textured visual background. In a yoked-control group, the reinforcer was independent of the subjects' responses, and the velocity gain remained unchanged (from 0.6 to 0.63, respectively, before and after training). In a control group that received no reinforcer, gain increased slightly after repetition of the task (from 0.63 to 0.71, respectively, before and after training). Using a model of pursuit, we show that these effects of learning can be simulated by modifying the gain of an extra-retinal signal. Our results demonstrate that learned contingencies can increase eye velocity in the absence of visual signals and support the view that pursuit is regulated by extra-retinal signals that can undergo long-term plasticity.
Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs (1984)

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.
(Invited) Crystalline Oxide Semiconductor Using CAAC-IGZO and its Application (2014)

It is revealed that c-axis aligned crystal In-Ga-Zn oxide(CAAC-IGZO) and nanocrystalline IGZO films are suitable for practical use due to their high-density crystalline morphologies and stability under electron beam irradiation in transmission electron microscope observation. We attempted to reproduce an amorphous IGZO film with no ordering. However, we found nanocrystals in the film and this film has low density and is soft, so that it is an unstable material in which crystals grow when subjected to electron beam irradiation in TEM observation. We fabricated field-effect transistors using CAAC-IGZO and examined their switching characteristics. As a result of microfabrication scaling, cutoff frequencies of 2 GHz and 1.5 GHz were obtained when the channel lengths were 60 nm and 100 nm, respectively. This opens new possibilities for oxide semiconductor large-scale integration.
An analytical model for the above-threshold characteristics of polysilicon thin-film transistors (1995)

An analytical model for the above-threshold characteristics of long-channel, small-grain and thin channel polysilicon thin film transistors (TFT's) is presented. This model is constructed by considering the barrier potential and the carrier trapping effect at grain boundaries of the channel. A band tail state located at E/sub c/-0.15 eV is taken into account to simulate the I-V characteristics. Based on the model, the theoretically simulated results show good agreement with experimental data of plasma-passivated and unpassivated TFT devices in a wide range of gate and drain biases and temperature. The correlation of transconductance to gate bias is also investigated. It is found that the decrease of grain-boundary barrier potential with gate voltage enhances the transconductance, while this enhancement effect becomes insignificant and causes a decrease of transconductance at high gate bias.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
T Lymphocyte-Directed Gene Therapy for ADA − SCID: Initial Trial Results After 4 Years (1995)

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.
Synthesis of some 3-(4-styryl-6-aryl-pyridin-2-yl)- and 3-(6-styryl-4-aryl-pyridin-2-yl) coumarins (2003)

Various 3-(4-styryl-6-aryl-pyridin-2-yl) coumarin s 4a-f and 3-(6-styryl-4-aryl-pyridin-2-yl) coumarins 5a-f have been sy nthesized by th e reaction of 3-coumarinoyl methyl pyridinium salt 1 with pentadienones 2a-f and 3a-f re spectectively in th e presence of ammonium acetate in refluxing aceti c acid. Coumarins having pyridine as a substituent group at 3 or 4 pos ition possess important biological activities like CNS depressants, monoamine oxidase inhibitors I, antifungal 2 , moth proofi ng 3 and bactericidal 4 . With a view to sy nth esizing such pyridyl coumarins having furth er substitution in the pyridine part, earlier we had reported the sy nthesis of variou s 3-(4,6-diary l pyridin2-yl )- and 8-(4,6-diaryl-pyridin-2-yl) coumarins 5 . In con tinu at ion of our interes t in the synthesis of pyridyl coumarins hav in g further sub stitution in pyridine moi ety we herein report th e sy nth es is of some 3-(4styryl-6- aryl-pyridin-2-yl ) coumarins 4a-f and 3-(6styryl-4-ary l-pyridin -2-yl) coumarins Sa-f. Styryl pyridines themse lv es possess varied biologi ­ cal properties like anthelmentics 6 , antimicrobial ?, plant growth regulators 8 , inhibitors of choline acetyl­ tran sferase 9 (CNS depressan t) and have interesting applications like liquid crystals 10, biosensors , acti va­ tors in detection of leukocytes in body fluid s '2 . Hence, it was thought worthwhile to incorporate a styryl pyridine moi ety in the coumarin nucleus. Thus in the present work various styryl sub stituted pyridy! cou­ marins 4a-f and 5a-f have been synthesized utili zin g the Krohenke' s pyridine synthesis l3 . To serve the pur­ pose two pentadienones viz. I,S -diaryl-2,4-pentadien­ I-one 2a-f and I ,S-diaryl-l ,4-pentadien-3-one 3a-f were se lected . The reaction of 3-cournarinoyl methyl pyridinium salt 1 with I ,S-diaryl-2,4-pent adi en-I-ones 2a-f in the presence of NH40Ac in refluxing acetic acid may re­ sult in the expected styryl pyridyl coumarins 4a-f (path-B) or may give ri se to a Michael adduct 6 (path­ A), as the pentadienones have two reactive sites for the Michael attack. Similarly the reaction of salt 1 with 1 ,5 -diaryl- l ,4-pentadien-3 -ones 3a-f in the pres ence of NH40Ac/AcOH may provide the expected coumarins 5a-f or may undergo doubi e Michael addi­ tion 14 to give 7 (Scheme I). Experimentally it was observed that the reaction of pyridinium salt 1 with the pentadienones 2a-f and 3a-f under Krohenke' s reaction condition afford a sin gle product correspond­ ing to the expected styryl pyridyl cournarins 4a-f and 5a-f respectiv ely. The structures of 3-(4-styryl-6-aryl­ pyridin-2-yl )coumari ns 4a-f and 3-(6-sty ryl-4- ary l­ pyridin-2- yl)cou marin s 5a-f were fully supported by physical data and spectral evidences (Tables I and II).
Detailed characterization of a cyclophilin from the human malaria parasite Plasmodium falciparum (1998)

Cyclosporin (Cs) A has pronounced antimalarial activity in vitro and in vivo. In other organisms, the drug is thought to exert its effects either by inhibiting the peptidylprolyl cis/trans isomerase activity of cyclophilin (CyP) or by forming a CyP-CsA complex that inhibits the phosphatase activity of calcineurin. We have cloned and overexpressed in Escherichia coli a gene encoding a CyP from Plasmodium falciparum (PfCyP19) that is located on chromosome 3. The sequence of PfCyP19 shows remarkable sequence identity with human CyPA and, unlike the two previously identified CyPs from P. falciparum, PfCyP19 has no signal peptide or N-terminal sequence extension, suggesting a cytosolic localization. All the residues implicated in the recognition of the synthetic substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide are conserved, resulting in characteristically high Michaelis-Menten and specificity constants (Km>>120 microM, kcat/Km=1.2x10(7) M-1.s-1 respectively). As the first line in the functional characterization of this enzyme, we have assessed its binding affinity for CsA. In accordance with its tryptophan-containing CsA-binding domain, PfCyP19 binds CsA with high affinity (Kd=13 nM, Ki=6.9 nM). Twelve CsA analogues were also found to possess Ki values similar to CsA, with the notable exceptions of Val2-Cs (Ki=218 nM) and Thr2-Cs (Ki=690 nM). The immunosuppressants rapamycin and FK506 were inactive as inhibitors, consistent with other members of the CyP family of rotamases. The CsA analogues were also assessed as inhibitors of P. falciparum growth in vitro. Although their antimalarial activity did not correlate with inhibition of enzyme activity, residues 3 and 4 of CsA appeared to be important for inhibition of parasite growth and residues 1 and 2 for PfCyP19 inhibition. We propose that a malarial CyP-CsA complex presents residues 3 and 4 as part of an 'effector surface' for recognition by a downstream target, similar to the proposed mechanism for T-cell immunosuppression.
Factors affecting the propagation of a B Cell Clone forming antibody to the 2,4‐dinitrophenyl group (1972)

Abstract We have studied the factors controlling the propagation and sequential transfer of B cell clone, E9, forming IgGI antibody to DNP in syngeneic CBA/H mice. The history of this clone is documented here in detail. E9 antibody was recognized by its isoelectric spectrum, detected by binding of 131 ‐DNP hapten after isoelectric focusing. During the life of this clone, induction of anti‐DNP depended on the presence of antigen (1 – 10 μg provided an optimum dose) and on cooperation with T‐derived cells recognizing carrier molecules. T cells contribute no information towards antibody formed by the B cells. During the first three transfer generations the clone produced high levels of E9 anti‐DNP (2 – 3 mg/ml serum) and the reliability of clonal transfer was high; 53/54 recipient mice formed large amounts of E9 antibody. As the proliferative capacity of the clone decreased, transfer became less reliable. The optimum interval between consecutive spleen cell transfers was 3 – 5 weeks, although successful transfer of memory cells could still be accomplished 65 days after last contact with antigen. The pI spectrum of E9 anti‐DNP remained constant throughout the life span of the clone, covering a period of one year and eight transfer generations and passage into 300 mice. We have therefore no evidence for any change or improvement in antibody produced by a single clone due to selective pressure. In other experimental series, limiting numbers (0.5 × 10 6 ‐ 2 × 10 6 ) of spleen cells primed with DNP‐BGG were distributed into irradiated syngeneic CBA/H mice. The incidence of single anti‐DNP‐forming clones sufficiently expanded for reliable sequential transfer is low; in 300 irradiated recipients we found 9 clones which produced high levels (0.3 ‐ 3 mg/ml) of anti‐DNP; some of these have been propagated by serial transfer. The high protein production appears to reflect overall expansion of the clone and to be a useful indicator of large numbers of memory cells. In general, low producing clones are not sufficiently expanded for effective propagation of the clone by serial spleen cell transfer.
A general and efficient route for chemical aminoacylation of transfer RNAs (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA general and efficient route for chemical aminoacylation of transfer RNAsStephanie A. Robertson, Jonathan A. Ellman, and Peter G. SchultzCite this: J. Am. Chem. Soc. 1991, 113, 7, 2722–2729Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/ja00007a055https://doi.org/10.1021/ja00007a055research-articleACS PublicationsRequest reuse permissionsArticle Views2165Altmetric-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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Webs of Research: Putting the User in Control (1998)

For over 40 years the citation databases from the Institute for Scientific Information (ISI) have provided a unique and incisive tool not just for researching the academic literature but for measuring and evaluating it as well. With the emergence of the World Wide Web this tool has been developed to place cited reference searching directly within the control of the user. Improved access to information is one feature of the Web, in particular through the mechanism of the Web link. The convergence of citation searching and Web linking towards citation linking will be examined in the paper with reference to two examples: Web of Science, a new service for scientists and social scientists from ISI, and an Open Journal of Cognitive Science developed by the Open Journal project. Web of Science provides links to the literature, links to holdings, to document delivery, and integration with bibliographic tools. Using citations -- the links made by authors themselves -- users can navigate between their current work and a priori work in the archives of the research literature or take a recent paper and move forward, tracking the citations dynamically. Literature searching is incomplete without links to the primary journal literature. The Open Journal of Cognitive Science, a collaborative work between the project and ISI, illustrates how the Web model of linking has been extended, linking from the abstracted literature to the full-text journal. Both implementations are illustrated in the paper.
The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas (2015)

Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204(+) tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14(+) monocytes upon long-term stimulation with RCC cells, and TIM-3-expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti-TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC.
PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases (1996)

The replication fidelities of Pfu, Taq, Vent, Deep Vent and UlTma DNA polymerases were compared using a PCR-based forward mutation assay. Average error rates (mutation frequency/bp/duplication) increased as follows: Pfu (1.3 x 10(-6)) < Deep Vent (2.7 x 10(-6)) < Vent (2.8 x 10(-6)) < Taq (8.0 x 10(-6)) < < exo- Pfu and UlTma (approximately 5 x 10(-5)). Buffer optimization experiments indicated that Pfu fidelity was highest in the presence of 2-3 mM MgSO4 and 100-300 microM each dNTP and at pH 8.5-9.1. Under these conditions, the error rate of exo- Pfu was approximately 40-fold higher (5 x 10(-5)) than the error rate of Pfu. As the reaction pH was raised from pH 8 to 9, the error rate of Pfu decreased approximately 2-fold, while the error rate of exo- Pfu increased approximately 9-fold. An increase in error rate with pH has also been noted for the exonuclease-deficient DNA polymerases Taq and exo- Klenow, suggesting that the parameters which influence replication error rates may be similar in pol l- and alpha-like polymerases. Finally, the fidelity of 'long PCR' DNA polymerase mixtures was examined. The error rates of a Taq/Pfu DNA polymerase mixture and a Klentaq/Pfu DNA polymerase mixture were found to be less than the error rate of Taq DNA polymerase, but approximately 3-4-fold higher than the error rate of Pfu DNA polymerase.
Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach. (1999)

Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese type 2 diabetic patients. Four patients were treated with sulfonylureas, and the remaining seven with diet therapy alone. None had diabetic retinopathy and microalbuminuria. Their fasting glucose level was 117+/-7 mg/dl (mean +/- SE), and HbA1c was 6.6+/-0.3%. Age-, sex-, and BMI-matched subjects with normal glucose tolerance served as control subjects. Plasma insulin response to the stimuli and insulin sensitivity indexes (S(I), S(I)*, and S(I)2* were derived from a minimal model and single- and two-compartment-labeled minimal models) were impaired in the type 2 diabetic patients. The combined ability of glucose, per se, to increase its own uptake and suppress EGP (glucose effectiveness [SG]), which was derived from kinetic analysis of plasma glucose by a minimal model, was significantly lower in the type 2 diabetic patients (0.0132+/-0.0015 vs. 0.0203+/-0.0022; P<0.05). However, the ability of glucose, per se, to stimulate glucose uptake, assessed as S(G)* and S(G)2* from the kinetic analysis of labeled glucose by single- and two-compartment minimal model, was not impaired in those patients. EGP of the type 2 diabetic patients as a whole was suppressed to the level similar to that of the control subjects despite a higher plasma glucose level throughout FSIGT. When EGP in the diabetic subjects was analyzed, considering their recent glycemic control, the initial suppression was blunted in the patients with higher HbA1c levels. In conclusion, glucose mass action to stimulate glucose uptake remains near-normal in the lean Japanese type 2 diabetic patients of this study, whereas ability of glucose to suppress EGP is impaired in the patients with recent hyperglycemia. This blunted suppression of EGP might be one of the conspirators for decreased S(G) in subjects with type 2 diabetes.
p53 expression during normal tissue regeneration in response to acute cutaneous injury in swine. (1994)

The present studies investigated the in vivo expression of the p53 suppressor gene and protein product in response to acute cutaneous injury in swine, along with the parallel expression of the c-sis/PDGF-B mitogen and its receptor beta (PDGF-R beta). p53 expression was shown to be suppressed during the period of active cellular proliferation in the injured tissue and to reemerge during the stages of healing. In contrast, c-sis/PDGF-B and PDGF-R beta were expressed during the early phase of active cellular proliferation and they were suppressed upon healing. This inverse relationship between mitogenic growth factors and p53 suggests the presence of well-controlled physiologic mechanisms that regulate in vivo the processes of normal tissue repair in response to injury. At the stages of tissue regeneration, these mechanisms include both the expression of growth factors that promote cell proliferation and the suppression of p53 that downregulates proliferation. At the stages of healing, the expression of the mitogenic growth factors is suppressed and that of p53 reemerges, reaching its peak at the time of complete epithelialization and healing of the injured tissue. These studies are the first to link the response of p53 protein to physiologic processes of tissue regeneration in vivo.
Synthesis and antitumor activity of 7-(N-glycosylamino)-indolo(3,2-b)quinolines. (1991)

Novel indolo[3,2-b]quinolines (1d-g), introduced at the 7-position with an N-glycosylamino group, were prepared and their antitumor activities against leukemia P388 in mice were examined. The N-Galactopyranosylamino derivative (1e) was a much more potent anti-leukemia compound (optimal dose = 25 mg/kg, T/C greater than 333%, cure 5/6) than lead compound 1a.