gebhart/patrepeval huggingface dataset:
Time course and cytokine dependence of human T-cell lymphotropic virus type 1 T-lymphocyte transformation as revealed by a microtiter infectivity assay (1995)

Human T-cell lymphotropic virus type 1 (HTLV-1) enhances the growth of T lymphocytes, allowing the generation of T-lymphocyte cell lines. This report describes a limiting-dilution assay system which uses low input numbers of HTLV-1-producing cells for generation of T-lymphocyte cultures. The HTLV-1 transformants generated with this assay system produced high levels of HTLV-1 p24 antigen and required exogenous cytokines for maintenance. Clonal populations of CD4- or CD8-positive HTLV-1 transformants were generated with transformation efficiency rates as high as 78%. An exogenous cytokine is necessary for HTLV-1 T-lymphocyte transformation, and cytokine dependence is the most likely outcome of infection and transformation. HTLV-1 T-lymphocyte transformation can occur in the presence of cytokines other than interleukin-2 (IL-2), such as IL-4 or IL-7. IL-4- or IL-7-dependent HTLV-1 transformants underwent T-lymphocyte mitogenesis in response to their homologous cytokines but proliferated best in the presence of IL-2. Since the receptors for IL-2, IL-4, and IL-7 share the IL-2 gamma chain, this component may be the common element in the signaling pathway for HTLV-1-associated transformation.
Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. (1997)

Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the migration of HT29 colonic carcinoma cells requires the perturbation of E-cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (< 1 minute) and specific tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor was detected in cells treated with recombinant rat TFF3. No phosphorylation of E-cadherin or alpha-catenin was detected. Tyrosine phosphorylation of beta-catenin was associated with reduced membranous E-cadherin expression, perturbation of intercellular adhesion, and promotion of cell motility. These results suggest that TFF3 enhances cell migration through modulation of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involved in this process.
Neuroprotection for the Warrior: Dietary Supplementation With Omega-3 Fatty Acids (2011)

Nutrition has traditionally involved in supplying energy and hydration. An emerging concept developed by the authors is the concept of using omega-3 fatty acids (n-3 FAs) to increase the resilience of the brain. The n-3 FAs have numerous proven benefits including support of cardiovascular and psychiatric health. Docosahexaenoic acid in particular, is found in high concentrations in the brain. N-3 FAs provide benefits by exerting a protective mechanism at the cellular and neuronal levels including the modulation of inflammatory cascade following traumatic brain injury. Promising research and evolving clinical experience now indicate that n-3 FA is useful and effective for recovery following traumatic brain injury. More exciting is that new laboratory research shows the beneficial effects extend to when n-3 FA is given before injury. Given the safety profile, availability, and affordability of n-3 FA, Generally Recognized As Safe amounts of eicosapentaenoic acid and docosahexaenoic acid (up to 3,000 mg daily) should be considered for the athlete and soldier, not only for its general health benefits, but particularly also for those at risk or high exposure to brain impacts. A comprehensive, coordinated research program to evaluate the multiple uses of n-3 FA should be a high priority for the Department of Defense.
The role of cathepsin L in malignant transformation. (1990)

Procathepsin L is the major excreted protein of malignantly transformed mouse fibroblasts and it is one of the major acid cysteine proteases in mammalian cells. The broad general protease activity of cathepsin L against a variety of extracellular matrix proteins as well as other intracellular protein substrates, and its regulation by factors which stimulate growth, suggest that it contributes to the transformed phenotype. Possible functions in antigen processing, invasiveness, metastasis, and turnover of intracellular and secreted proteins involved in growth regulations have been proposed.
Architecture Support for Improving Bulk Memory Copying and Initialization Performance (2009)

Bulk memory copying and initialization is one of the most ubiquitous operations performed in current computer systems by both user applications and Operating Systems. While many current systems rely on a loop of loads and stores, there are proposals to introduce a single instruction to perform bulk memory copying. While such an instruction can improve performance due to generating fewer TLB and cache accesses, and requiring fewer pipeline resources, in this paper we show that the key to significantly improving the performance is removing pipeline and cache bottlenecks of the code that follows the instructions. We show that the bottlenecks arise due to (1) the pipeline clogged by the copying instruction, (2) lengthened critical path due to dependent instructions stalling while waiting for the copying to complete, and (3) the inability to specify (separately) the cacheability of the source and destination regions. We propose FastBCI, an architecture support that achieves the granularity efficiency of a bulk copying/ initialization instruction, but without its pipeline and cache bottlenecks. When applied to OS kernel buffer management, we show that on average FastBCI achieves anywhere between 23% to 32% speedup ratios, which is roughly 3x-4x of an alternative scheme, and 1.5x-2x of a highly optimistic DMA with zero setup and interrupt overheads.
The Aspergillus toxin restrictocin is a suitable cytotoxic agent for generation of immunoconjugates with monoclonal antibodies directed against human carcinoma cells (1989)

The protein toxin restriction, isolated from the mould Aspergillus restrictus, inactivates protein synthesis in eukaryotic cells by blocking the ribosome elongation cycle. This protein acts as a specific nuclease that cuts off a small fragment from the 28-S rRNA. Biochemical and biological characterization of this toxin indicated that it is a non-glycosylated polypeptide of Mr 16836, exhibiting in cell-free systems a protein synthesis inhibition capacity similar to that of the ricin A chain. This polypeptide seemed unable to penetrate most of the cancer cell lines tested, as measured by its low in vitro cytotoxicity. In addition in vivo studies in BALB/c mice demonstrated that restriction toxicity was very low and that in rabbits, after intravenous injection 15% of the toxin was still present in the blood stream 24 h later. After derivatization with N-succinimidyl 3-(2-pyridyldithio)propionate and reduction by dithiothreitol, the restrictocin maintained its protein synthesis inhibitory activity, as assayed in a cell-free system. This derivatized toxin was then coupled to monoclonal antibodies (MBr1, MLuC1, MLuC2, MOv17, MOv18, MOv19) which exhibited a restricted spectrum of reactivity against human carcinomas. The biochemical and biological characterization of the immunoconjugates indicated that (a) when restrictocin was coupled to monoclonal antibodies with an average molar ratio of about 2, the immunoconjugates maintained the binding activity of the antibody and protein synthesis inhibition activity of the toxin; (b) four immunoconjugates were tested for cytotoxicity and three of them obtained with the MBr1, MLuC1 and MOv17 monoclonal antibodies exhibited a good level of cytotoxicity for relevant target cells and low or no toxicity for the irrelevant cell lines. The MLuC2 monoclonal antibody which gave rise to a completely ineffective immunoconjugate, induced internalization of less than one tenth of the antigenic sites whereas the MBr1, MLuC1 and MOv17 monoclonal antibodies exhibited about one third of the antigenic sites interanalized. From these data it is concluded that, providing an appropriate target antigen and coupling procedure are selected, restrictocin can be considered a suitable toxin for immunoconjugate generation.
Evaluation of the Effect of Neptune Krill Oil on Chronic Inflammation and Arthritic Symptoms (2007)

The results of the present study clearly indicate that NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and 14 days.
Microarray Analysis of the Mycobacterium tuberculosis Transcriptional Response to the Acidic Conditions Found in Phagosomes (2002)

We used microarrays and real-time reverse transcription-PCR to analyze the global transcriptional response of Mycobacterium tuberculosis to low pH in vitro, which may mimic an environmental signal encountered by phagocytosed mycobacteria. Eighty-one genes were differentially expressed >1.5-fold, including many involved in fatty acid metabolism. The most highly induced genes showed homology with nonribosomal peptide synthetases/polyketide synthases.
Electrohydrodynamic Precipitator (1962)

A contaminated fluid is charged and pumped into an electrodeless collection space, where particulates are precipitated. An approximate theory of precipitation is given; it is supported by experimental evidence. The method is especially suited for cleaning insulating liquids.
Catalytic Asymmetric Synthesis of Alkynyl Aziridines: Both Enantiomers of cis‐Aziridines from One Enantiomer of the Catalyst (2014)

Alkynyl aziridines can be obtained from the catalytic asymmetric aziridination (AZ reaction) of alkynyl imines with diazo compounds in high yields and high asymmetric inductions mediated by a chiral boroxinate or BOROX catalyst. In contrast to the AZ reaction with aryl- and alkyl-substituted imines, alkynyl imines react to give cis-substituted aziridines with both diazo esters and diazo acetamides. Remarkably, however, the two diazo compounds give different enantiomers of the cis-aziridine from the same enantiomer of the catalyst. Theoretical considerations of the possible transition states for the enantiogenic step reveal that the switch in enantiomers results from a switch from Si-face to Re-face addition to the imine, which in turn is related to a switch from reaction with an E-imine in the former and a Z-isomer of the imine in the latter.
Course and outcome of hepatitis C (2002)

The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
Human β-Secretase (BACE) and BACE Inhibitors (2003)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTHuman β-Secretase (BACE) and BACE InhibitorsVarghese John, James P. Beck, Michael J. Bienkowski, Sukanto Sinha, and Robert L. HeinriksonView Author Information Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, California 94080, and Pfizer Corporation, 301 Henrietta Street, Kalamazoo, Michigan 49007 Cite this: J. Med. Chem. 2003, 46, 22, 4625–4630Publication Date (Web):September 24, 2003Publication History Received20 May 2003Published online24 September 2003Published inissue 1 October 2003https://pubs.acs.org/doi/10.1021/jm030247hhttps://doi.org/10.1021/jm030247hreview-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views2612Altmetric-Citations125LEARN 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 SUBJECTS:Central nervous system,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Robust Consensus in the Presence of Impulsive Channel Noise (2015)

A distributed average consensus algorithm robust to a wide range of impulsive channel noise distributions is proposed. This work is the first of its kind in the literature to propose a consensus algorithm which relaxes the requirement of finite moments on the communication noise. It is shown that the nodes reach consensus asymptotically to a finite random variable whose expectation is the desired sample average of the initial observations with a variance that depends on the step size of the algorithm and the receiver nonlinear function. The asymptotic performance is characterized by deriving the asymptotic covariance matrix using results from stochastic approximation theory. Simulations corroborate our analytical findings and highlight the robustness of the proposed algorithm.
Fluorescence lifetime imaging endoscopy (2011)

We present two FLIM endoscopes for clinical imaging and in vivo cell biology. For subcellular confocal imaging we demonstrated the first confocal FLIM endomicroscope, implementing TCSPC with a Cellvizio&#174;GI, which we have now developed as a self-contained wheeled instrument (1.0 &times; 0.7 m) incorporating a tunable excitation laser and acquiring images in &lt; 10 s. This has been applied to image FRET in live cells and to image tissue autofluorescence, for which we are implementing "FIFO" for image montaging. For diagnostic screening/guided biopsy, we have developed a complementary wide-field FLIM endoscope employing time-gated detection with violet and UV excitation for imaging over mm-cm fields of view.
Long-Term High-Titer Neutralizing Activity Induced by Octameric Synthetic HIV-1 Antigen (1991)

A titer for homologous viral neutralization activity (greater than 1:19,683) was observed after a 3.5-year immunization period with an octameric, branching peptide representing the principal neutralizing determinant (PND) of the human immunodeficiency virus-1IIIB envelope protein. Booster immunizations elicited persistent and potent antibodies in guinea pigs, exceeding responses produced by a conventional bovine serum albumin conjugate by 100-fold. Peptide length, central presentation of a conserved sequence, and inclusion of an upstream sequence contributed to immunogenicity. Titers (greater than 1:1,000) of heterotypic neutralizing antibodies also developed. Octameric PND peptides are a promising approach for an acquired immunodeficiency syndrome (AIDS) vaccine.
Neutralizing antibody response during acute and chronic hepatitis C virus infection (2004)

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximately 50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication.
Principles of Plant Breeding (1961)

INTRODUCTORY TOPICS. Darwinian Evolution. Origins of Agriculture. Evolution During Domestication. Mating Systems of Plants. Overview of Plant Breeding. BIOLOGICAL FOUNDATIONS OF PLANT BREEDING. Heredity and Environment. Genetic Consequences of Hybridization. Inheritance of Continuously Varying Characters: Biometrical Genetics. Evolution During Cultivation. Marker-Assisted Analysis of Adaptedness in Nature. Marker-Assisted Dissection of Adaptedness in Cultivation. MODERN BREEDING PLANS. Reproductive Systems and Breeding Plans. Breeding Self-Pollinated Plants. Breeding Hybrid Varieties of Outcrossing Plants. Breeding Clonally Propagated Plants. Breeding Hybrid Varieties of Selfing Plants and Plants that Are Clonally Propagated in Nature. Plant Breeding for Low-Input Agricultures. Glossary. References. Index.
Histone Deacetylases Specifically Down-regulate p53-dependent Gene Activation (2000)

p53, the most commonly mutated gene in cancer cells, directs cell cycle arrest or induces programmed cell death (apoptosis) in response to stress. It has been demonstrated that p53 activity is up-regulated in part by posttranslational acetylation. In agreement with these observations, here we show that mammalian histone deacetylase (HDAC)-1, -2, and -3 are all capable of down-regulating p53 function. Down-regulation of p53 activity by HDACs is HDAC dosage-dependent, requires the deacetylase activity of HDACs, and depends on the region of p53 that is acetylated by p300/CREB-binding protein (CBP). These results suggest that interactions of p53 and HDACs likely result in p53 deacetylation, thereby reducing its transcriptional activity. In support of this idea, GST pull-down and immunoprecipitation assays show that p53 interacts with HDAC1 both in vitro and in vivo. Furthermore, a pre-acetylated p53 peptide was significantly deacetylated by immunoprecipitated wild type HDAC1 but not deacetylase mutant. Also, co-expression of HDAC1 greatly reduced the in vivo acetylation level of p53. Finally, we report that the activation potential of p53 on the BAX promoter, a natural p53-responsive system, is reduced in the presence of HDACs. Taken together, our findings indicate that deacetylation of p53 by histone deacetylases is likely to be part of the mechanisms that control the physiological activity of p53.
Preclinical evaluation of gemcitabine/paclitaxel-interactions in human bladder cancer lines. (2004)

The combination of gemcitabine and paclitaxel in vitro yields superior cytotoxic efficacy, if given simultaneously or with gemcitabine first. While in vitro cell models may not necessarily predict clinical outcome, they do provide a basis for rational scheduling of drugs in clinical trials.
Establishment, Maintenance, and In Vitro and In Vivo Applications of Primary Human Glioblastoma Multiforme (GBM) Xenograft Models for Translational Biology Studies and Drug Discovery (2011)

Development of clinically relevant tumor model systems for glioblastoma multiforme (GBM) is important for advancement of basic and translational biology. One model that has gained wide acceptance in the neuro-oncology community is the primary xenograft model. This model entails the engraftment of patient tumor specimens into the flank of nude mice and subsequent serial passage of these tumors in the flank of mice. These tumors are then used to establish short-term explant cultures or intracranial xenografts. This unit describes detailed procedures for establishment, maintenance, and utilization of a primary GBM xenograft panel for the purpose of using them as tumor models for basic or translational studies.
Cellular Immunotherapy of Cancer: An Overview and Future Directions (2017)

The clinical success of checkpoint inhibitors has led to a renaissance of interest in cancer immunotherapies. In particular, the possibility of ex vivo expanding autologous lymphocytes that specifically recognize tumor cells has attracted much research and clinical trial interest. In this review, we discuss the historical background of tumor immunotherapy using cell-based approaches, and provide some rationale for overcoming current barriers to success of autologous immunotherapy. An overview of adoptive transfer of lymphocytes, tumor infiltrating lymphocytes and dendritic cell therapies is provided. We conclude with discussing the possibility of gene-manipulating immune cells in order to augment therapeutic activity, including silencing of the immune-suppressive zinc finger orphan nuclear receptor, NR2F6, as an attractive means of overcoming tumor-associated immune suppression.