gebhart/patrepeval huggingface dataset:
TRAIL/Apo-2-ligand-induced apoptosis in human T cells (1998)

Members of the tumor necrosis factor (TNF) family such as CD95 (APO-1/Fas) ligand (L) trigger apoptosis in lymphoid cells. Recently, a new member of apoptosis-inducing ligands, TRAIL (TNF-related-apoptosis-inducing-ligand)/Apo-2 ligand, was identified that might act in a similar way. We compared TRAIL and CD95L-induced apoptosis in human lymphoid cells. Expression of TRAIL was found in CD4+ and CD8 T cells following activation, suggesting that TRAIL participates in T cell-mediated induction of apoptosis. Similar to CD95L, TRAIL-induced apoptosis in target cells is mediated by activation of caspases (ICE/Ced-3 proteases). However, different human lymphoid cell lines and peripheral T cells differ in sensitivity towards induction of apoptosis by TRAIL and CD95L. In addition, T cells are highly sensitive towards CD95L-induced apoptosis after prolonged activation in vitro, but remain completely resistant to TRAIL-induced apoptosis. In contrast, T cells from HIV-1-infected patients previously shown to exhibit increased CD95 sensitivity are even more susceptible towards TRAIL-induced cell death. These data suggest that TRAIL might participate in CD95-independent apoptosis of lymphoid cells and might be involved in deregulated apoptosis in diseases such as leukemias and HIV-1 infection.
The Trifluoromethyl Group in Medical Chemistry (1959)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTThe Trifluoromethyl Group in Medical ChemistryHarry L. YaleCite this: J. Med. Chem. 1958, 1, 2, 121–133Publication Date (Print):April 1, 1959Publication History Published online1 May 2002Published inissue 1 April 1959https://pubs.acs.org/doi/10.1021/jm50003a001https://doi.org/10.1021/jm50003a001research-articleACS PublicationsRequest reuse permissionsArticle Views3323Altmetric-Citations166LEARN 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
Reducing the Dimensionality of Data with Neural Networks (2006)

High-dimensional data can be converted to low-dimensional codes by training a multilayer neural network with a small central layer to reconstruct high-dimensional input vectors. Gradient descent can be used for fine-tuning the weights in such "autoencoder" networks, but this works well only if the initial weights are close to a good solution. We describe an effective way of initializing the weights that allows deep autoencoder networks to learn low-dimensional codes that work much better than principal components analysis as a tool to reduce the dimensionality of data.
Role of interleukin‐7 in T‐cell development from hematopoietic stem cells (1998)

All lymphocytes are derived from hematopoietic stem cells (HSC). The interleukin-7 receptor (IL-7R) transduces non-redundant signals for both T and B-cell development from HSC. The upregulation of the IL-7R occurs at the stage of the clonogenic common lymphoid progenitor, a recently identified population that can give rise to all lymphoid lineages (T, B and natural killer cells) at a single cell level. The IL-7R plays a critical role in the rearrangement of immunoglobulin heavy chain genes required for B-cell development. IL-7R expression is critically regulated in developing thymocytes; thymocytes that fail the positive selection process downregulate the IL-7R, but those undergoing positive selection upregulate or maintain IL-7R expression. Recent data indicate that IL-7 signaling enhances the survival of developing thymocytes and mature T cells, presumably by its upregulating Bcl-2. Detailed analysis of the signaling cascades activated by the IL-7R may help to reveal the differential roles of IL-7 signaling in T and B-cell development.
Cell surface receptor binding of phospholipid . protein complexes containing different ratios of receptor-active and -inactive E apoprotein. (1980)

Previous data have shown that apo-E HDL, a lipoprotein containing only the E apoprotein, bind to fibroblast cell surface receptors with a higher affinity than do the apo-€3-containing low density lipoproteins (LDL).The enhanced affinity of apo-E NDL, results from multiple receptor binding (four receptors per HDL, particle).To study the molecular interaction of the E apoprotein with the lipoprotein receptors, apo-E was formed in a complex with dimyristoylphosphatidylcholine vesicles, and the equilibrium dissociation constants (&) for the binding of these complexes with the receptor were determined.In the dimyristoylphosphatidylcholine apoprotein complexes, the ratio of active apo-E, which was capable of receptor binding, to inactive apo-E, which was made incapable of receptor binding by acetoacetylation of the lysine residues, was varied.No differences were noted in the physicochemical properties of the complexes formed with either the active apo-E, inactive apo-E, or different ratios of the two.The complexes had a molecular weight of 760,000 and contained approximately 4 apo-E molecules/disk.Complexes which contained 4 active apo-E molecules bound with a & of 0.10 X IO-' M, a binding affinity similar to that of apo-E HDL, ( K d = 0.12 X lo-' M).Reduction in the number of active apo-E molecules per complex resulted in a reduction in binding affinity and an increase in the number of disks bound per cell.Complexes with 1 active and 3 inactive apo-E molecules/disk bound with an affinity (& --2.6 x IO-' M)similar to the binding affinity of LDL (& --2.7 X lo-' M).The data show that the higher binding affinity of apo-E HDL, resulted from binding to multiple LDL receptors and that the binding affinity of complexes containing 1 active apo-E molecule was similar to the binding affinity of the apo-B-containing LDL.The original work of Goldstein and Brown (1) has shown that cultured human fibroblasts, as well as other cell types, possess specific receptors on their cell surface that bind to the apo-B-containing low density lipoproteins (LDL)' with high * The costs of publication of this article were defrayed in part b. y the payment of page charges.
The Fetal Glycoprotein, Fetuin, Counteracts Ill-Effects of the Bacterial Endotoxin, Lipopolysaccharide, in Pregnancy (1998)

We show that fetuin, a fetal glycoprotein present in fetal plasma in concentrations substantially higher than in the adult, can exert a protective function against ill-effects of the bacterial endotoxin, lipopolysaccharide (LPS), in pregnancy. The concentration of fetuin in plasma of pregnant rats (E17 gestation) was artificially increased by repeated intraperitoneal administration of this protein. This was followed by an injection of a standard dose of LPS, a dose that produced in control animals (no additional fetuin) nearly 50% abortions and 40% maternal deaths. None of the females exposed to increased fetuin died following LPS injection. Nine out of 10 multigravida animals carried their pregnancy to full term but all primagravidas aborted.
Rationalizable Strategic Behavior (1984)

This paper examines the nature of rational choice in strategic games.Although there are many reasons why an agent might select a Nash equilibrium strategy in a particular game, rationality alone does not require him to do so.A natural extension of widely accepted axioms for rational choice under uncertainty to strategic environments generates an alternative class of strategies, labelled "rationalizable."It is argued that no rationalizable strategy can be discarded on the basis of rationality alone, and that all rationally justifiable strategies are members of the rationalizable set.The properties of rationalizable strategies are studied, and refinements are considered.PROOF OF PROPOSITION 5.5: Since under the specified conditionsf(-) is a contraction mapping, Nash equilibrium is unique.We need only show P(G) = N*(G).Since P(G) is the intersection of an infinite sequence of compact, nested sets, it is compact.Consequently, we can define di = max d(s,, s,).s,,s, E-P,(G) Assume without loss of generality that d, > di Vi > 1.If point rationalizable strategies are not unique, then di > 0. Let s' and sj' be the strategies for which d(s'1, sj') = dl.There must exist t', t' e P(G)such that fl(t') = sj, and fl(t") = sj', with g,(t') = v1(t") (the first component doesn't effect fl( )).Now d(t', t") < ( d2 ) < d1(I-1)1/2. (i=2 J Further, d(f(t'), f(t")) > d(s', sj') = dl.So d(f(t), ft"))> d(t, t"I(I 1 ,/2
Improved synthesis of 4-alkoxybenzyl alcohol resin (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImproved synthesis of 4-alkoxybenzyl alcohol resinGui-shen Lu, Svetlana Mojsov, James P. Tam, and R. B. MerrifieldCite this: J. Org. Chem. 1981, 46, 17, 3433–3436Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August 1981https://pubs.acs.org/doi/10.1021/jo00330a009https://doi.org/10.1021/jo00330a009research-articleACS PublicationsRequest reuse permissionsArticle Views944Altmetric-Citations73LEARN 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
Arterial pulse wave haemodynamics (2012)

The shape of the arterial pulse wave is intimately related to the physical properties of the cardiovascular system. Understanding the mechanisms underlying this relation is clinically relevant, since pulse waveforms carry valuable information for the diagnosis and treatment of disease. We overview some numerical, theoretical and experimental efforts (using in vivo and in vitro data) made in this field of research, focusing on the physical aspects of arterial pulse wave propagation in the systemic circulation. The mathematical and numerical tools that we describe are based on the one-dimensional formulation in the time-domain.
Immunological characterization of recombinant antigens isolated from a Mycobacterium avium lambda gt11 expression library by using monoclonal antibody probes (1991)

Nontuberculous mycobacteria, particularly Mycobacterium avium, have been isolated from a significant percentage of patients with AIDS. Early detection of M. avium infection is difficult, and treatment regimens are often ineffective. Much needs to be learned about antigens and factors responsible for immunity to and pathogenesis of the disease. Specific antigens and diagnostic procedures for infection need to be developed. To address some of these problems, we have generated 25 different monoclonal antibodies against a serovar 4 strain of M. avium isolated from a patient with AIDS. Protease sensitivity studies have demonstrated that each of these antibodies recognizes a protein-associated epitope. Immunoblot analyses suggest that seven of these monoclonal antibodies react specifically with M. avium and M. intracellular epitopes. Immunoreactive bacteriophages were identified from an M. avium lambda gt11 expression library with two of these monoclonal antibodies (3808 C3 and 3954 B12). Lambda lysogens, generated from the immunoreactive bacteriophages, overproduced beta-galactosidase fusion proteins which were reactive with the two monoclonal antibodies in immunoblot assays. The purified fusion proteins were shown to elicit skin test reactions in sensitized guinea pigs.
Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D 1 antagonists (2001)

The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (S(D)) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and S(D)s were withheld. The effects of reexposure to the S(D) on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine S(D), but not the non-reward S(D), elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine S(D) were both reversed by selective dopamine D(1) receptor antagonists. The undiminished efficacy of the cocaine S(D) to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D(1)-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.
Aminoboranediyl-Bridged Zirconocenes:  Highly Active Olefin Polymerization Catalysts (1999)

Novel aminoboranediyl-bridged zirconocenes [i-Pr2NB(η5-C5H4)2]ZrCl2 (8b) and [i-Pr2NB(η5-1-C9H8)2]ZrCl2 (4b) have been prepared and structurally characterized. When activated by excess methylaluminoxane, 4b and 8b form highly active catalysts for the polymerization of ethylene. The catalyst derived from 4b converts propylene to isotactic polypropylene.
Augmentation strategies in treatment-resistant affective disorders (1991)

Treatment resistance contributes significantly to the morbidity associated with mood disorders. We examined the recent literature on augmentation of standard treatments with thyroid hormone, lithium, carbamazepine, fluoxetine or fenfluramine. While the efficacy of lithium augmentation is supported, thyroid augmentation is disappointing other than for a subgroup of rapid cyclers. Preliminary evidence for the efficacy of other strategies is also discussed
Botulinum toxin therapy for neurologic disorders (1992)

In the last 20 years, the therapeutic uses of botulinum toxin, a potent neurotoxin, have been investigated. The agent produces chemical denervation of muscle, thereby causing atrophy and weakness. Studies have shown that injection of this agent is an effective therapy for focal dystonias, particularly blepharospasm, hemifacial spasm, and torticollis. Investigation continues into the role of botulinum toxin in the treatment of anismus, detrusor-sphincter dyssynergia, writers' cramp, and other disorders in which focal weakening of selected muscles could be useful.
Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. (1996)

We have investigated responses to extracellular ATP (ATPe) in the microglial cell lines N9 and N13 and in freshly isolated mouse microglial cells. Upon stimulation with this nucleotide, N9 and N13 cells underwent an increase in the cytoplasmic free Ca2+ concentration ([Ca2+]i), a sustained depolarization of the plasma membrane, and an uptake of extracellular markers such as ethidium bromide and lucifer yellow; increases in plasma membrane permeability were paralleled by striking morphologic changes. ATPe, as well as other nucleotides, activated a spiking Ca2+ release from intracellular stores; however, only ATPe was also able to cause a massive transmembrane Ca2+ influx. The ATP analogue 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) triggered a sustained Ca2+ influx accompanied by little release from stores. The ATP derivative oxidized ATP (oATP) strongly inhibited Ca2+ influx, minimally affecting Ca2+ release. From ATPe-sensitive microglial cell lines, we selected several ATPe-resistant clones that showed complete lack of ATPe-mediated plasma membrane permeability changes, although they retained the Ca2+ mobilization response from intracellular stores. ATPe-dependent plasma membrane permeability changes were also greatly reduced in growth-arrested microglial cells. Finally, ATPe triggered IL-1 beta release from wild-type but not ATPe-resistant microglial cells. These results show that microglial cells express at least two purinergic receptor subtypes, metabotropic (P2Y) and ionotropic (P2Z), and that the latter is modulated during cell cycle and coupled to IL-1 beta release.
Protein-sequence studies on Rh-related polypeptides suggest the presence of at least two groups of proteins which associate in the human red-cell membrane (1988)

The Rh D blood-group antigen forms part of a complex, involving several other polypeptides, that is deficient in the red cells of individuals who lack all the antigens of the Rh blood-group system (Rhnull red cells). These include components recognized by anti-(Rh D) antibodies and the murine monoclonal antibodies R6A and BRIC 125. We have carried out protein-sequence studies on the components immunoprecipitated by these antibodies. Anti-(Rh D) antibodies immunoprecipitate an Mr-30,000-32,000 polypeptide (the D30 polypeptide) and an Mr-45,000-100,000 glycoprotein (D50 polypeptide). Antibody R6A immunoprecipitates two glycoproteins of Mr 31,000-34,000 (R6A32 polypeptide) and Mr 35,000-52,000 (R6A45 polypeptide). The D30 and R6A32 polypeptides were found to have the same N-terminal amino acid sequences, showing that they are closely related proteins. The D50 polypeptide and the R6A45 polypeptide also had indistinguishable N-terminal amino acid sequences that differed from that of the D30 and R6A32 polypeptides. The putative N-terminal membrane-spanning segments of the two groups of proteins showed homology in their amino acid sequence, which may account for the association of each of the pairs of proteins during co-precipitation by the antibodies. Supplementary data related to the protein sequence have been deposited as Supplementary Publication SUP 50417 (6 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1988) 249, 5.
Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with activation of cyclin-dependent kinases 1 and 2. (1995)

7-Hydroxystaurosporine (UCN-01) is a potent inhibitor of protein kinase C (PKC) isozymes alpha, beta, and gamma [Seynaeve et al., Mol. Pharmacol, 45: 1207-1214, 1994] that also has antitumor effects in vivo. To determine whether inhibition of PKC can be related to inhibition of cell growth with induction of apoptosis, we compared the effects of UCN-01 to those of the highly selective bisindolylmaleimide PKC antagonist GF 109203X in leukemic T-cell lines. Both compounds potently inhibited PKC activity when added to T-cell membrane preparations and reversed phorbol ester-induced c-fos gene expression in intact cells. However, whereas UCN-01 potently inhibited growth of Jurkat, Molt-3, Molt-4, and Hut-78 cells (IC50 = 20-65 nM, irreversible after 24 h of exposure), GF 109203X had IC50s for cell growth of 3.6-5.0 muM. Less than 3 h after addition, UCN-01 but not GF 109203X-treated cells displayed loss of cells with G2-M DNA content, appearance of a hypodiploid DNA fraction, and evidence of internucleosomal DNA fragmentation. Six h after treatment, cells appeared to accumulate with S-phase DNA content. These effects correlated with selective UCN-01 but not GF 109203X-induced decrease in total and tyrosine phosphorylation of cyclin-dependent kinases (cdks) 1 and 2, and with increases in the histone H1 kinase activities of cdk1 and cdk2. UCN-01 was relatively less potent in inhibition of properly activated cdk1 and cdk2 when added in vitro to H1 kinase assays (IC50 = 1000 and 600 nM, respectively). We conclude that inhibition of PKC alone is not sufficient to account for the actions of UCN-01 and are led to the hypothesis that inappropriate cdk activation either correlates with or actually mediates cell growth inhibition with apoptosis in T lymphoblasts exposed to UCN-01.
Nuclear Export of NF-ATc Enhanced by Glycogen Synthase Kinase-3 (1997)

The transcription factor NF-AT responds to Ca2+-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). GSK-3 phosphorylates conserved serines necessary for nuclear export, promotes nuclear exit, and thereby opposes Ca2+-calcineurin signaling. Because GSK-3 responds to signals initiated by Wnt and other ligands, NF-AT family members could be effectors of these pathways.
Do photobleached fluorescent microtubules move?: re-evaluation of fluorescence laser photobleaching both in vitro and in growing Xenopus axon. (1993)

We previously documented differences in the behavior of microtubules in growing axons of two types of neurons, adult mouse sensory neurons and Xenopus embryonal spinal cord neurons. Namely, the bulk of microtubules was stationary in mouse sensory neurons both by the method of photoactivation of caged-fluorescein-labeled tubulin and photobleaching of fluorescein-labeled tubulin, but the bulk of microtubules did translocate anterogradely by the method of photoactivation. Although these results indicated that the stationary nature of photobleached microtubules in mouse neurons is not an artifact derived from the high levels of energy required for the procedure, it has not yet been settled whether the photobleaching method can detect the movement of microtubules properly. Here we report photobleaching experiments on growing axons of Xenopus embryonal neurons. Anterograde movement of photobleached microtubules was observed at a frequency and translocation rate similar to the values determined by the method of photoactivation. Our results suggest that, under appropriate conditions, the photobleaching method is able to reveal the behavior of microtubules as accurately as the photoactivation method.