gebhart/patrepeval huggingface dataset:
Tumor-Specific CD4+ T Lymphocytes from Cancer Patients Are Required for Optimal Induction of Cytotoxic T Cells Against the Autologous Tumor (2000)

This study focuses on the specific CD4+ T cell requirement for optimal induction of cytotoxicity against MHC class II negative autologous tumors (AuTu) collected from patients with various types of cancer at advanced stages. CD4+ T cells were induced in cultures of cancer patients' malignant effusion-associated mononuclear cells with irradiated AuTu (mixed lymphocyte tumor cultures (MLTC)) in the presence of recombinant IL-2 and recombinant IL-7. Tumor-specific CD4+ T cells did not directly recognize the AuTu cells, but there was an MHC class II-restricted cross-priming by autologous dendritic cells (DCs), used as APC. CD8+ CTL, also induced during the MLTC, lysed specifically AuTu cells or DCs pulsed with AuTu peptide extracts (acid wash extracts (AWE)) in an MHC class I-restricted manner. Removal of CD4+ T cells or DCs from the MLTC drastically reduced the CD8+ CTL-mediated cytotoxic response against the AuTu. AWE-pulsed DCs preincubated with autologous CD4+ T cells were able, in the absence of CD4+ T cells, to stimulate CD8+ T cells to lyse autologous tumor targets. Such activated CD8+ T cells produced IL-2, IFN-gamma, TNF-alpha, and GM-CSF. The process of the activation of AWE-pulsed DCs by CD4+ T cells could be inhibited with anti-CD40 ligand mAb. Moreover, the role of CD4+ T cells in activating AWE-pulsed DCs was undertaken by anti-CD40 mAb. Our data demonstrate for the first time in patients with metastatic cancer the essential role of CD4+ Th cell-activated DCs for optimal CD8+ T cell-mediated killing of autologous tumors and provide the basis for the design of novel protocols in cellular adoptive immunotherapy of cancer, utilizing synthetic peptides capable of inducing T cell help in vivo.
Evaluating the levels of CSF and serum factors in ALS (2017)

We demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.
Engineering of Human Pluripotent Stem Cells by AAV-mediated Gene Targeting (2010)

Precise genetic manipulation of human pluripotent stem cells will be required to realize their scientific and therapeutic potential. Here, we show that adeno-associated virus (AAV) gene targeting vectors can be used to genetically engineer human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Different types of sequence-specific changes, including the creation and correction of mutations, were introduced into the human HPRT1 and HMGA1 genes (HPRT1 mutations being responsible for Lesch-Nyhan syndrome). Gene targeting occurred at high frequencies in both ESCs and iPSCs, with over 1% of all colony-forming units (CFUs) undergoing targeting in some experiments. AAV vectors could also be used to target genes in human fibroblasts that were subsequently used to derive iPSCs. Accurate and efficient targeting took place with minimal or no cytotoxicity, and most of the gene-targeted stem cells produced were euploid and pluripotent.
Peptide synthesis using the four-component condensation (Ugi reaction) (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPeptide synthesis using the four-component condensation (Ugi reaction)Michinori Waki and Johannes MeienhoferCite this: J. Am. Chem. Soc. 1977, 99, 18, 6075–6082Publication Date (Print):August 1, 1977Publication History Published online1 May 2002Published inissue 1 August 1977https://pubs.acs.org/doi/10.1021/ja00460a039https://doi.org/10.1021/ja00460a039research-articleACS PublicationsRequest reuse permissionsArticle Views966Altmetric-Citations49LEARN 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
Protection against trojan horses by source code analysis (1994)

Abstract The technology of security in computer networks has far‐reaching implications. In this paper, assuming a UNIX network system, which is the most popular currently, we enumerate the threats against security and classify the problems. Among the problems so defined, we consider particularly the Trojan horse problem, which is important when a program is received from the outside; and we propose a method of protection against Trojan horses. In the proposed protection method, objects which have been modified by the source program are extracted and are compared with a previously prepared list (the condition list) of objects which should not have been modified. In this method, verification of the security of the program needs to be done only at the time of its installation, so there is no loss in efficiency of performance at run time. Also, we can prevent security violations which cannot be regulated by controlling access and flow. In the proposed method, the major problem is determining the extent to which altered objects can be detected. In this regard, we perform soine experiments on the free software X11R4 and TeX. Finally, based on the results of the experiments, we evaluate the proposed protection method on the security of programs imported from the outside.
Independent folding of the carboxyl-terminal fragment 228-316 of thermolysin (1984)

The COOH-terminal fragment 206-316 of thermolysin was shown previously to maintain a stable folded structure in aqueous solution comparable to that of the corresponding region in native thermolysin and thus to possess protein domain characteristics [Fontana, A., Vita, C., & Chaiken, I. M. (1983) Biopolymers 22, 69-78]. In order to study the effect of polypeptide chain length on folding and stability of an isolated domain, the 111 amino acid residue fragment was shortened on the NH2-terminal side by removal of a 22-residue segment. Treatment of fragment 206-316 with hydroxylamine under alkaline conditions permitted selective cleavage of the Asn227-Gly228 peptide bond, and from the reaction mixture fragment 228-316 was isolated in homogeneous form. This fragment appeared to attain in aqueous solution the folding properties of the corresponding segment in the intact protein, as indicated by quantitative analysis of secondary structure from far-ultraviolet circular dichroism spectra and immunological properties. Thus, double-immunodiffusion analyses showed that fragment 228-316 is able to recognize and precipitate anti-thermolysin antibodies raised in rabbits with native thermolysin as immunogen. The fragment displayed fully reversible and cooperative conformational transitions mediated by pH, heat, and guanidine hydrochloride (Gdn.HCl), as expected for a globular protein species. Thermal denaturation of the fragment in aqueous solution at pH 7.8 showed a Tm of 66 degrees C and the Gdn.HCl-mediated unfolding a midpoint transition at 2.2 M denaturant concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Near-infrared optical imaging of proteases in cancer. (2003)

Near-infrared optical imaging is a newer imaging technique that, coupled with sensitive enzymatically specific fluorescent beacons, shows much promise for earlier detection of many cancers and their in situ characterization. On the basis of animal studies demonstrating visualization of micrometastasis-sized tumors and the ability to evaluate therapeutic enzyme inhibition real-time, such imaging may be incorporated in the clinical imaging paradigm in the future, both to improve cancer screening as well as for monitoring therapy in individual patients. This review details some of the related biology, optical probe design, and required hardware, with in vivo cathepsin and matrix metalloprotinease imaging used as examples.
Intrapericardial administration of basic fibroblast growth factor: Myocardial and tissue distribution and comparison with intracoronary and intravenous administration (2003)

Growth factor-induced angiogenesis is being investigated in ischemic heart disease. Intracoronary and intravenous delivery are the most practical, but are limited by low myocardial uptake and significant systemic recirculation. The pericardial space may act as a drug delivery reservoir with increased myocardial uptake and reduced systemic toxicities. This study was designed to investigate the myocardial and tissue deposition and retention of basic fibroblast growth factor (FGF-2) after intrapericardial administration in normal and chronically ischemic animals. Twelve Yorkshire pigs were used for the study [six normal and six animals with chronic myocardial ischemia (ameroid constrictor on LCx)] with bolus intrapericardial administration of (125)I-FGF-2 (25 micro Ci) with 30 micro g of cold FGF-2 and 3 mg of heparin. Tissue and myocardial distribution was determined at 1 and 24 hr by measuring (125)I-bFGF-specific activity. In addition, regional myocardial deposition was determined using (125)I-bFGF activity and organ level autoradiography. The heart (pericardium and myocardium) accounted for the majority of (125)I-bFGF activity in ischemic animals (30.9% at 1 hr and 23.9% at 24 hr). Left anterior descending artery territory activity/gm of tissue for nonischemic and ischemic animals was 0.01% and 0.01% at 1 hr and 0.0009% and 0.12% at 24 hr, respectively. LCx territory activity for nonischemic and ischemic animals was 0.006% and 0.008% at 1 hr and 0.03% and 0.05% at 24 hr, respectively. Endocardial activity was low at all time points. Liver uptake was 0.47% (nonischemic) and 0.34% (ischemic) at 1 hr and 0.23% (nonischemic) and 0.54% (ischemic) at 24 hr. Intrapericardial delivery of FGF-2 provides markedly higher myocardial deposition and retention and lower systemic recirculation than intracoronary or intravenous delivery at the expense of poor subendocardial penetration. This limitation, however, did not affect its efficacy.
Survivin antisense compound inhibits proliferation and promotes apoptosis in liver cancer cells (2005)

Down-regulation of survivin expression induced by the antisense compounds reduces tumor growth potential, promotes apoptosis and affects the localization of survivin proteins in HepG2 cells. Furthermore, survivin protein is a key molecule associated with proliferation and apoptosis, and antisense oligonucleotides targeting survivin have a bright prospect in the therapy of liver cancer.
Reliable prediction of T‐cell epitopes using neural networks with novel sequence representations (2003)

In this paper we describe an improved neural network method to predict T-cell class I epitopes. A novel input representation has been developed consisting of a combination of sparse encoding, Blosum encoding, and input derived from hidden Markov models. We demonstrate that the combination of several neural networks derived using different sequence-encoding schemes has a performance superior to neural networks derived using a single sequence-encoding scheme. The new method is shown to have a performance that is substantially higher than that of other methods. By use of mutual information calculations we show that peptides that bind to the HLA A*0204 complex display signal of higher order sequence correlations. Neural networks are ideally suited to integrate such higher order correlations when predicting the binding affinity. It is this feature combined with the use of several neural networks derived from different and novel sequence-encoding schemes and the ability of the neural network to be trained on data consisting of continuous binding affinities that gives the new method an improved performance. The difference in predictive performance between the neural network methods and that of the matrix-driven methods is found to be most significant for peptides that bind strongly to the HLA molecule, confirming that the signal of higher order sequence correlation is most strongly present in high-binding peptides. Finally, we use the method to predict T-cell epitopes for the genome of hepatitis C virus and discuss possible applications of the prediction method to guide the process of rational vaccine design.
Human gut microbiota does not ferment erythritol (2005)

Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.
Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. (1988)

Inhibitors of DNA methylation, such as 5-azacytidine, induce gene expression. We have previously reported that cloned T cells treated with 5-azacytidine lose the requirement for Ag and can be activated by autologous HLA-D molecules alone, thus becoming auto-reactive. This phenomenon could potentially mediate an autoimmune disease in vivo. Inasmuch as several drugs are known to cause autoimmune disease, we asked whether they exert the same effects on T cells as 5-azacytidine. We report that hydralazine and procainamide, two drugs associated with a lupus-like autoimmune disease, also inhibit DNA methylation and induce self-reactivity in cloned T cell lines. These results suggest that drug-induced autoimmune disease may be due to activation of as yet unidentified genes through mechanisms involving DNA methylation.
Activated nitriles in heterocyclic synthesis. The reaction of cinnamonitrile derivatives with active methylene reagents (1984)

Abstract The reaction of substituted cinnamonitrile derivatives with cyanoacetanilide and with ethyl acetoacetate produced several new polyfunctional pyridine and pyran derivatives. Evidence for assigned structure of the reaction products and the possible mechanisms of their formation is presented.
Development of integrated cable/telephony in the United Kingdom (1995)

The United Kingdom offers franchised cable television operators the unique opportunity to provision a competitive telephony service in addition to multichannel television services. The TeleWest Communications Group Plc., a joint venture between Telecommunication Inc. (TCI) and US West, have taken advantage of this opportunity to invest, operate, and assist in the operation of CATV/telephony in the United Kingdom. TeleWest owns or invests in 24 franchises, totalling approximately 3.6 million homes passed. Twenty-one of the 24 franchises wholly owned or invested in by TeleWest are offering competitive telephony as of the end of 1994. Others are set to start in the 1995-96 time frame. The article discusses the development of network architectures in support of TeleWest's cable/telephony opportunities in the United Kingdom. The article begins with an account of the history of U.K. cable/telephony, continues with the early developments and drivers of the architecture, discusses the current architecture and build, and concludes with an overview of future development and directions for the architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Medical treatment of epilepsy (2003)

The licensing of new antiepileptic drugs (AEDs) has led to a marked increase in the pharmaceutical armamentarium available for the treatment of epilepsy since 1990. The new drugs have now secured their place in the pharmacotherapy of epilepsy. The main reason for their success is their good general tolerability (especially with regard to cognitive function), the low rate of drug–drug interaction and the high anticonvulsant potency of some of the compounds. It is fortunate that many of the new AEDs have also proven effective in the treatment of generalised seizures, although they were originally developed for the treatment of focal seizures. However, the wide treatment choice has not solved the problems associated with the medical treatment of epilepsy. In monotherapy, none of the new AEDs have been shown to be superior in their potency to control seizures to older AEDs in comparative studies. Nonetheless, the greater choice of drugs allows treatment to be better tailored to the requirements of individual patients. Now there is a need to study patients whose seizures were not controlled by initial or alternative monotherapy to create an evidence-base for truly rational combination therapy in the future. Additional improvements in the medical treatment of epilepsy may come from AEDs currently in development, many of which use novel or unknown modes of action. So far, however, there is no evidence that any of these compounds will have radically different effects from the drugs currently available, or that they will have antiepileptic rather than purely anticonvulsant potential.
Emergency Decisionmaking During the State of Florida's Response to Hurricane Andrew* (1993)

This article focuses attention on emergency decisionmaking during the State of Florida's response to Hurricane Andrew, the nation's costliest natural disaster.
Structure of Acyl Carrier Protein Bound to FabI, the FASII Enoyl Reductase from Escherichia coli (2006)

Acyl carrier proteins play a central role in metabolism by transporting substrates in a wide variety of pathways including the biosynthesis of fatty acids and polyketides. However, despite their importance, there is a paucity of direct structural information concerning the interaction of ACPs with enzymes in these pathways. Here we report the structure of an acyl-ACP substrate bound to the Escherichia coli fatty acid biosynthesis enoyl reductase enzyme (FabI), based on a combination of x-ray crystallography and molecular dynamics simulation. The structural data are in agreement with kinetic studies on wild-type and mutant FabIs, and reveal that the complex is primarily stabilized by interactions between acidic residues in the ACP helix alpha2 and a patch of basic residues adjacent to the FabI substrate-binding loop. Unexpectedly, the acyl-pantetheine thioester carbonyl is not hydrogen-bonded to Tyr(156), a conserved component of the short chain alcohol dehydrogenase/reductase superfamily active site triad. FabI is a proven target for drug discovery and the present structure provides insight into the molecular determinants that regulate the interaction of ACPs with target proteins.
Heat Shock Protein 90 Mediates Protein-protein Interactions between Human Aminoacyl-tRNA Synthetases (2000)

Heat shock protein 90 (hsp90) is a molecular chaperone responsible for protein folding and maturation in vivo. Interaction of hsp90 with human glutamyl-prolyl-tRNA synthetase (EPRS) was found by genetic screening, co-immunoprecipitation, and in vitro binding experiments. This interaction was sensitive to the hsp90 inhibitor, geldanamycin, and also ATP, suggesting that the chaperone activity of hsp90 is required for interaction with EPRS. Interaction of EPRS with hsp90 was targeted to the region of three tandem repeats linking the two catalytic domains of EPRS that is also responsible for the interaction with isoleucyl-tRNA synthetase (IRS). Interaction of EPRS and IRS also depended on the activity of hsp90, implying that their association was mediated by hsp90. EPRS and IRS form a macromolecular protein complex with at least six other tRNA synthetases and three cofactors. hsp90 preferentially binds to most of the complex-forming enzymes rather than those that are not found in the complex. In addition, inactivation of hsp90 interfered with the in vivo incorporation of the nascent aminoacyl-tRNA synthetases into the multi-ARS complex. Thus, hsp90 appears to mediate protein-protein interactions of mammalian tRNA synthetases.
Metabolism, Nutrition, and Function of Carotenoids (1986)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Purification and Properties of Extracellular and Cell-bound Cellulase Components of Pseudomonas fluorescens var. cellulosa (1970)

Journal Article Purification and Properties of Extracellular and Cell-bound Cellulase Components of Pseudomonas fluorescens var. cellulosa Get access KUNIO YAMANE, KUNIO YAMANE Botanical Institute, Tokyo Kyoiku UniversityOtsuka, Tokyo Search for other works by this author on: Oxford Academic PubMed Google Scholar HIROSHI SUZUKI, HIROSHI SUZUKI Botanical Institute, Tokyo Kyoiku UniversityOtsuka, Tokyo Search for other works by this author on: Oxford Academic PubMed Google Scholar KAZUTOSI NISIZAWA KAZUTOSI NISIZAWA Botanical Institute, Tokyo Kyoiku UniversityOtsuka, Tokyo Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 67, Issue 1, January 1970, Pages 19–35, https://doi.org/10.1093/oxfordjournals.jbchem.a129231 Published: 01 January 1970 Article history Received: 24 May 1969 Published: 01 January 1970
Distinct Mechanisms Contribute to Stringent Substrate Specificity of Tissue-type Plasminogen Activator (1996)

Tissue-type plasminogen activator (t-PA) has evolved to optimize cleavage of plasminogen (Plg) while minimizing cleavage of other potential protein and peptide substrates. We find that the S2 and S2 subsites of t-PA are important determinants of specificity, and occupancy of the S3 subsite is essential for catalysis. t-PA efficiently hydrolyzes a protein substrate which incorporates an optimized substrate sequence, revealing the ability of the protease to participate in the highly selective cleavage of protein fusions. Surprisingly, t-PA cleaves this engineered protein substrate with a Km that is reduced 950-fold relative to the Km for hydrolysis of the same target sequence within a peptide. This reduction of Km suggests that binding is facilitated by interactions between protein substrate and protease that are distant from the P4-P2' residues. We use this kinetic data to derive a model in which several distinct mechanisms contribute to the remarkable specificity of t-PA.