gebhart/patrepeval huggingface dataset:
Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT-type) require CD40-mediated signaling and Th2-type cytokines for in vitro growth and differentiation. (1997)

To investigate the mechanisms of T cell dependence underlying the development of extranodal mucosa-associated lymphoid tissue (MALT)-type B cell lymphomas, the activation, proliferation, and differentiation of lymphoma B cells were studied using ligand binding to the CD40 membrane receptor. The activation and proliferative response of all investigated low-grade MALT-type lymphomas (n = 6) was strongly dependent on anti-CD40-mediated signals and was complemented by cytokines produced by T helper cells of the Th2 type (interleukin-4 (IL-4) and/or IL-10). Th1 cytokines (IL-2 and/or interferon-gamma) bad little effect. Low-grade, but less so high-grade, MALT-type lymphoma B cells were induced to secrete large amounts of tumor immunoglobulin in response to IL-10. In contrast, high-grade MALT-type lymphomas (n = 5) proliferated in response to both Th2- and Th1-type cytokines and CD40 stimulation, whereas Burkitt lymphomas (n = 3) could not be rescued from apoptosis by CD40 stimulation with or without cytokines. These results suggest that CD40 signaling in combination with Th2 cytokines are essential for the development and progression of low-grade MALT-type B cell lymphoma. We conclude that T cells, which activate B cells in a CD40-dependent fashion, may contribute to lymphoma pathogenesis.
Regeneration of Transgenic Soybean (Glycine max) Plants from Electroporated Protoplasts (1992)

Transgenic soybean (Glycine max [L.] Merr.) plants were regenerated from calli derived from protoplasts electroporated with plasmid DNA-carrying genes for a selectable marker, neomycin phosphotransferase (NPTII), under the control of the cauliflower mosaic virus 35-Svedberg unit promoter, linked with a nonselectable mannityl opine synthesis marker. Following electroporation and culture, the protoplast-derived colonies were subjected to kanamycin selection (50 micrograms per milliliter) beginning on day 15 for 6 weeks. Approximately, 370 to 460 resistant colonies were recovered from 1 x 10(6) electroporated protoplasts, giving an absolute transformation frequency of 3.7 to 4.6 x 10(-4). More than 80% of the kanamycin-resistant colonies showed NPTII activity, and about 90% of these also synthesized opines. This indicates that the linked marker genes were co-introduced and co-expressed at a very high frequency. Plants were regenerated from the transformed cell lines. Southern blot analysis of the transformed callus and leaf DNA demonstrated the integration of both genes. Single-plant assays performed with different plant parts showed that both shoot and root tissues express NPTII activity and accumulate opines. Experiments with NPTII and mannityl opine synthesis marker genes on separate plasmids resulted in a co-expression rate of 66%. These results indicate that electroporation can be used to introduce both linked and unlinked genes into the soybean to produce transformed plants.
Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships (1990)

A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.
Nuclear transport of plant potyviral proteins. (1990)

We have used immunoblotting, immunocytochemical, and gene fusion methods to examine the differential subcellular partitioning of tobacco etch potyvirus proteins that are potentially associated with RNA replication. From the earliest timepoints at which viral proteins could be detected, proteins Nla (49-kilodalton proteinase) and Nlb (58-kilodalton polymerase) were localized primarily in the nucleus, whereas the 71-kilodalton cylindrical inclusion protein was identified in the cytoplasm. The Nla and Nlb coding regions were fused to the beta-glucuronidase (GUS) sequence in a plant expression vector, resulting in synthesis of chimeric proteins in transfected protoplasts and in transgenic plants. In situ localization of GUS activity revealed nuclear localization of the GUS-Nla and GUS-Nlb fusion proteins and cytoplasmic localization of nonfused GUS. These results indicate that both Nla and Nlb contain nuclear targeting signals, and that they may serve as useful models for studies of plant cell nuclear transport. A discussion of the general utility of the nuclear transport system described here, as well as the role of nuclear translocation of potyviral proteins, is presented.
The positive prognostic effect of stromal CD8+ tumor-infiltrating T cells is restrained by the expression of HLA-E in non-small cell lung carcinoma (2015)

CD8+ T cell infiltration strongly contributes to a better prognosis in NSCLC when the tumor cells retain the expression of classical HLA class I and do not express HLA-E. Therefore, analysis of HLA-A, -B/C and HLA-E expression should be included as biomarkers to predict the response to immunotherapy.
Truncated glucagon‐like peptide I, an insulin‐releasing hormone from the distal gut (1987)

By hydrophobic gel permeation and high pressure liquid chromatography we isolated from pig intestinal mucosa a peptide which corresponds to proglucagon 78–107 as suggested by chromatography and determination of its N‐terminal sequence. Natural and synthetic proglucagon 78–107 dose dependently and potently increased insulin secretion from the isolated perfused pig pancreas. Proglucagon 78–107 also secreted by the small intestine may participate in the hormonal control of insulin secretion.
Translation of Poliovirus mRNA (1990)

Ribosome binding to cellular eukaryotic mRNAs is proposed to occur by initial attachment at or near the mRNA 5' cap structure (m7 GppN, where N is any nucleotide) followed by scanning till the appropriate initiator AUG is encountered. A pivotal aspect of this model is the obligatory entry of the ribosomes at the 5' end of the mRNA (regardless if it contains a cap structure). Recent experiments, however, demonstrated that ribosomes can access certain mRNAs by internal binding to the 5'-untranslated region. This was most clearly demonstrated for members of the picornavirus family such as poliovirus and encephalomyocarditis virus. Further experiments suggest that other viral mRNAs and even cellular mRNAs may use similar mechanisms of ribosome binding. Here we describe some features of the poliovirus 5'-untranslated region and possible trans-acting factors that are involved in this mechanism of translation.
Purification of Piscirickettsia salmonis and partial characterization of antigens (1998)

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, an economically significant disease affecting the salmon aquaculture industry. As with other rickettsial pathogens, antigenic analysis of P. salmonis has been limited by the inherent difficulties of purifying an intracellular organism away from host cell material. In this report, we describe the use of diatrizoate meglumine and diatrizoate sodium (DMDS) density gradient centrifugation to purify P. salmonis grown in chinook salmonis was consistently concentrated in a visible band within the DMDS density gradient at density of 1.15 to 1.16 g ml(-1). Recovery of purified, viable organisms from DMDS density gradients varied from 0.6 to 3%. Preparations of uninfected CHSE-214 cells, CHSE-214 cells infected with P. salmonis, and gradient-purified P. salmonis were compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis to assess the degree of purification and to identify P. salmonis-specific proteins. Although gradient-purified P. salmonis preparations were not completely free of host cell material, 8 bacterial proteins were identified. Polyclonal rabbit antiserum was used in an immunoblot of proteins from purified P. salmonis to identify 3 major and 5 minor antigens. The major antigens of 56, 30 and 20 kDa were potential candidates for experimental vaccines and development of novel diagnostic assays.
Ethereum: A Secure Decentralised Generalised Transaction Ledger (2013)

The blockchain paradigm when coupled with cryptographically-secured transactions has demonstrated its
utility through a number of projects, not least Bitcoin. Each such project can be seen as a simple application on a decentralised, but singleton, compute resource. We can call this paradigm a transactional singleton machine with shared-state.
Ethereum implements this paradigm in a generalised manner. Furthermore it provides a plurality of such resources, each with a distinct state and operating code but able to interact through a message-passing framework with others. We discuss its design, implementation issues, the opportunities it provides and the future hurdles we envisage.
Fucosyltransferase-producing sialyl Lea and sialyl Lex carbohydrate antigen in benign and malignant gastrointestinal mucosa (1994)

The expression of sialyl Le(a) and sialyl Le(x) antigens in the stomach and the colon was not controlled solely by fucosyltransferases but by a more complicated system involving other glycosyltransferases.
Phonetic training and language modeling for word spotting (1993)

The authors present a view of HMM (hidden Markov model)-based word spotting systems as described by three main components: the HMM acoustic model; the overall HMM structure, including nonkeyword modeling; and the keyword scoring method. They investigate and present comparative results for various approaches to each of these components and show that design choices for these components can be addressed separately. They also present a novel approach to word spotting that combines phonetic training, large vocabulary modeling, and statistical language modeling with a posterior probability approach to keyword scoring. They perform word spotting experiments using telephone quality conversational speech from the Switchboard corpus to examine the effect of different design choices for the three components and demonstrate that the proposed approach provides superior performance to previously used techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An Evolutionarily Conserved Region in the Second lntron of the Human Nestin Gene Directs Gene Exmession to CNS Progenitor Cells and to Early Neural Ciest Cells (1997)

Central nervous system (CNS) progenitor cells transiently proliferate in the embryonic neural tube and give rise to neurons and glial cells. A characteristic feature of the CNS progenitor cells is expression of the intermediate filament nestin and it was previously shown that the rat nestin second intron functions as an enhancer, directing gene expression to CNS progenitor cells. In this report we characterize the nestin enhancer in further detail. Cloning and sequence analysis of the rat and human nestin second introns revealed local domains of high sequence similarity in the 3' portion of the introns. Transgenic mice were generated with the most conserved 714 bp in the 3' portion of the intron, or with the complete, 1852 bp, human second intron, coupled to the reporter gene lacZ. The two constructs gave a very similar nestin-like expression pattern, indicating that the important control elements reside in the 714 bp element. Expression was observed starting in embryonic day (E)7.5 neural plate, and at E10.5 CNS progenitor cells throughout the neural tube expressed lacZ. At E12.5, lacZ expression was more restricted and confined to proliferating regions in the neural tube. An interesting difference, compared to the rat nestin second intron, was that the human intron at E10.5 mediated lacZ expression also in early migrating neural crest cells, which is a site of endogenous nestin expression. In conclusion, these data show that a relatively short, evolutionarily conserved region is sufficient to control gene expression in CNS progenitor cells, but that the same region differs between rodents and primates in its capacity to control expression in neural crest cells.
Novel Cyclopentadienyl Tricarbonyl99mTc Complexes Containing 1-Piperonylpiperazine Moiety: Potential Imaging Probes for Sigma-1 Receptors (2014)

We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl (99m)Tc complexes as potent σ1 receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for σ1 receptors and moderate to high selectivity for σ2 receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding (99m)Tc derivatives [(99m)Tc]23 and [(99m)Tc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [(99m)Tc]23 or [(99m)Tc]24 in the brain. Studies of the cellular uptake of [(99m)Tc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [(99m)Tc]23 to σ1 receptors in the tumor.
The QUIC Transport Protocol (2017)

We present our experience with QUIC, an encrypted, multiplexed, and low-latency transport protocol designed from the ground up to improve transport performance for HTTPS traffic and to enable rapid deployment and continued evolution of transport mechanisms. QUIC has been globally deployed at Google on thousands of servers and is used to serve traffic to a range of clients including a widely-used web browser (Chrome) and a popular mobile video streaming app (YouTube). We estimate that 7% of Internet traffic is now QUIC. We describe our motivations for developing a new transport, the principles that guided our design, the Internet-scale process that we used to perform iterative experiments on QUIC, performance improvements seen by our various services, and our experience deploying QUIC globally. We also share lessons about transport design and the Internet ecosystem that we learned from our deployment.
Arabidopsis Contains a Large Superfamily of Acyl-Activating Enzymes. Phylogenetic and Biochemical Analysis Reveals a New Class of Acyl-Coenzyme A Synthetases (2003)

Acyl-activating enzymes are a diverse group of proteins that catalyze the activation of many different carboxylic acids, primarily through the formation of a thioester bond. This group of enzymes is found in all living organisms and includes the acyl-coenzyme A synthetases, 4-coumarate:coenzyme A ligases, luciferases, and non-ribosomal peptide synthetases. The members of this superfamily share little overall sequence identity, but do contain a 12-amino acid motif common to all enzymes that activate their acid substrates using ATP via an enzyme-bound adenylate intermediate. Arabidopsis possesses an acyl-activating enzyme superfamily containing 63 different genes. In addition to the genes that had been characterized previously, 14 new cDNA clones were isolated as part of this work. The protein sequences were compared phylogenetically and grouped into seven distinct categories. At least four of these categories are plant specific. The tissue-specific expression profiles of some of the genes of unknown function were analyzed and shown to be complex, with a high degree of overlap. Most of the plant-specific genes represent uncharacterized aspects of carboxylic acid metabolism. One such group contains members whose enzymes activate short- and medium-chain fatty acids. Altogether, the results presented here describe the largest acyl-activating enzyme family present in any organism thus far studied at the genomic level and clearly indicate that carboxylic acid activation metabolism in plants is much more complex than previously thought.
Decrease in Activity of Glutathione Reductase Enhances Paraquat Sensitivity in Transgenic Nicotiana tabacum (1995)

Transgenic tobacco (Nicotiana tabacum L. cv SR1) with decreased activity of glutathione reductase exhibited enhanced sensitivity to paraquat in the light as evaluated by chlorophyll destruction and electrolyte leakage from leaf discs. This result indicates the involvement of glutathione reductase in the tolerance of plants to photooxidative stress caused by the herbicide.
Circular dichroism analysis of ligand-induced conformational changes in protein kinase C. Mechanism of translocation of the enzyme from the cytosol to the membranes and its implications (1993)

The structural changes following the binding to protein kinase C (PKC) of activators that promote its translocation to lipid environments were studied by far-u.v. c.d. and intrinsic fluorescence measurements of the protein. In the absence of activators, PKC contained 40% alpha-helix, with an average size of 13 amino acids per alpha-helix segment, and 12% beta-structure as deduced from c.d. spectral analysis while fitting a set of model proteins of known structure. Ligands that promote translocation and activation of the enzyme, such as Ca2+ ions and phorbol esters, produced drastic changes in the c.d. spectra which may be interpreted as a reduction in the average number of consecutive amino acids in the alpha-helix. Most of the total alpha-helix structure was conserved and an increase in beta-structure was produced by active phorbol esters. These activators differentially affected the fluorescence of PKC: phorbol esters shifted the emission maximum to the red, whereas Ca2+ produced a marked decrease in the intensity of the fluorescence emission, suggesting in both cases that tryptophan residues were exposed to increased polar environments after binding of the ligands.
Interkinase domain of kit contains the binding site for phosphatidylinositol 3' kinase. (1992)

Our previous analysis of the signal transduction pathway used by the c-kit-encoded receptor for the stem cell factor (SCF) indicated efficient coupling to the type I phosphatidylinositol 3' kinase (PI3K). In an attempt to localize the receptor's site of interaction with PI3K, we separately deleted either the noncatalytic 68-amino-acid-long interkinase domain or the carboxyl-terminal portion distal to the catalytic sequences. Loss of ligand-induced association of PI3K with the former deletion mutant and retention of the PI3K association by the carboxyl-terminally deleted receptor implied interactions of PI3K with the kinase insert. This was further supported by partial inhibition of the association by an anti-peptide antibody directed against the kinase insert and lack of effect of an antibody directed to the carboxyl tail of the SCF receptor. A bacterially expressed kinase insert domain was used as a fusion protein to directly test its presumed function as a PI3K association site. This protein bound PI3K from cell lysate as demonstrated by PI3K activity and by an associated phosphoprotein of 85 kDa. The association was dependent on phosphorylation of the tyrosine residues on the expressed kinase insert. On the basis of these observations, we conclude that the kinase insert domain of the SCF receptor selectively interacts with the p85 regulatory subunit of PI3K and that this association requires phosphorylation of tyrosine residues in the kinase insert region, with apparently no involvement of the bulk cytoplasmic structure or tyrosine kinase function of the receptor.
Impaired Generation of Anti‐Viral Cytotoxicity against Lymphocytic Choriomeningitis and Vaccinia Virus in Mice Treated with CD4‐Specific Monoclonal Antibody (1989)

The role of CD4 + helper T cells in induction of anti‐viral cytotoxic T‐cell response was investigated by treating normal and thymectomized C57B1/6 mice with CD4‐speciflc monoclonal antibodies (MoAb). In CD4‐specific MoAb‐treated mice infected with Vaccinia or lymphocytic choriomeningitis virus (LCMV), cytotoxic T‐cell activity was 5–15 times lower than in normal controls when measured in a 51 Cr release assay and computed as lytic units 6 and 8 days respectively after virus inoculation. This difference in the levels of effector T‐cell activities did not reflect slower kinetics of cytotoxic T‐cell induction in antibody‐treated versus control mice, since it was also obvious at 8 days after infection for Vaccinia virus and 10 and 12 days after inoculation with LCMV, CD4‐specific MoAb‐induced inhibition of cytotoxic T‐cell responses in vivo was seen up to 150 days after treatment in thymectomized mice. However, no significant suppressive effect of the same antibody treatment on T‐cell cytotoxicity could be observed in animals treated on day 3 or later after infection with Vaccinia virus. Injection of CD4‐depleted mice with recombinant interleukin 2 (rIL‐2) partially corrected the impaired virus‐specific cytotoxic T‐cell response, suggesting that IL‐2 supply may be limiting in mice licking T helper cells.
Molecular targets for existing and novel immunosuppressive drugs (2000)

Anti-neoplastic cytostatic antiproliferative agents, such as methotrexate, 6-mercaptopurine and cyclophosphamide, were originally used as immunosuppressive drugs. Although these agents induced only modest anti-rejection activity, they caused serious non-specific bone marrow suppression, impairing host resistance and increasing the incidence of infections. Unlike these non-selective agents, cyclosporine A, tacrolimus and sirolimus act more selectively on different stages of the T-lymphocyte (T-cell) and B-lymphocyte (B-cell) activation cycles; however, cyclosporine and tacrolimus are nephrotoxic, whereas sirolimus causes hypertriglyceridaemia. Thus, despite this progress, continued efforts must be made to develop and test new, potentially very selective agents. The agent 15-deoxyspergualin moderately inhibits both mitogen-stimulated T-cell proliferation and the generation of cytotoxic T lymphocytes (CTLs) but does not affect the production of interleukin 2 (IL-2). Another drug, FTY720, has a unique action to prevent rejection, by altering the homing of lymphocytes to the lymphoid compartments. The newest members of the family of antiproliferative agents, namely mycophenolate mofetil, leflunomide and brequinar, are potentially more selective than their predecessors. However, the most promising agents are produced using antisense technology. This approach involves the design of antisense oligodeoxynucleotides; these novel drugs are designed to block allograft rejection by blocking selected messenger RNA (mRNA). This review outlines the mechanisms of action, the limitations of application and the molecular or cellular targets of traditional agents, newly developed drugs and also antisense technology, which is an example of a new application of molecular medicine.