gebhart/patrepeval huggingface dataset:
Cell-mediated immune responses in healthy children with a history of subclinical infection with Japanese encephalitis virus: analysis of CD4+ and CD8+ T cell target specificities by intracellular delivery of viral proteins using the human immunodeficiency virus Tat protein transduction domain (2004)

Japanese encephalitis virus (JEV), a single-stranded positive-sense RNA virus of the family Flaviviridae, is the major cause of paediatric encephalitis in Asia. The high incidence of subclinical infections in Japanese encephalitis-endemic areas and subsequent evasion of encephalitis points to the development of immune responses against JEV. Humoral responses play a central role in protection against JEV; however, cell-mediated immune responses contributing to this end are not fully understood. The structural envelope (E) protein, the major inducer of neutralizing antibodies, is a poor target for T cells in natural JEV infections. The extent to which JEV non-structural proteins are targeted by T cells in subclinically infected healthy children would help to elucidate the role of cell-mediated immunity in protection against JEV as well as other flaviviral infections. The property of the Tat peptide of Human immunodeficiency virus to transduce proteins across cell membranes, facilitating intracellular protein delivery following exogenous addition to cultured cells, prompted us to express the four largest proteins of JEV, comprising 71 % of the JEV genome coding sequence, as Tat fusions for enumerating the frequencies of virus-specific CD4(+) and CD8(+) T cells in JEV-immune donors. At least two epitopes recognized by distinct HLA alleles were found on each of the non-structural proteins, with dominant antiviral Th1 T cell responses to the NS3 protein in nearly 96 % of the cohort. The data presented here show that non-structural proteins are frequently targeted by T cells in natural JEV infections and may be efficacious supplements for the predominantly antibody-eliciting E-based JEV vaccines.
Recommendations for the use of medications with continuous enteral nutrition (2009)

There was a lack of published data regarding drug-nutrient interactions for a majority of the drugs commonly administered to patients receiving continuous enteral nutrition. Clinicians should recognize potential drug-nutrient interactions and use available evidence to optimize patients' drug therapy.
Controlling biological interfaces on the nanometer length scale (2009)

A number of techniques currently exist that allow researchers to generate spatially resolved patterns of chemistry and topography on the nanometer length scale. Both chemically and topographically nanopatterned surfaces can be generated to more accurately mimic the natural extracellular environment. Chemically patterned surfaces can also be used to study tightly controlled and highly specific cell-cell and cell-substrate interactions or to create increasingly densely packed biosensors. From a biological standpoint, these methods enable fabrication of elaborate interfaces to mechanistically study the effects of cell adhesion ligand density, spacing, clustering, and spatial distribution on cell fate and function. The most commonly used nanopatterning techniques in the biomaterials arena are reviewed here, including scanning probe, electron beam, colloidal, and imprint lithographies, critically examining the resolution available and the scalability of the technique for generating the number of surfaces necessary for statistically relevant cell culture studies.
Distributed Source Localization in Wireless Underground Sensor Networks (2011)

Node localization plays an important role in many practical applications of wireless underground sensor networks (WUSNs), such as finding the locations of earthquake epicenters, underground explosions, and microseismic events in mines. It is more difficult to obtain the time-difference-of-arrival (TDOA) measurements in WUSNs than in terrestrial wireless sensor networks because of the unfavorable channel characteristics in the underground environment. The robust Chinese remainder theorem (RCRT) has been shown to be an effective tool for solving the phase ambiguity problem and frequency estimation problem in wireless sensor networks. In this paper, the RCRT is used to robustly estimate TDOA or range difference in WUSNs and therefore improves the ranging accuracy in such networks. After obtaining the range difference, distributed source localization algorithms based on a diffusion strategy are proposed to decrease the communication cost while satisfying the localization accuracy requirement. Simulation results confirm the validity and efficiency of the proposed methods.
Expression profiling in lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 reveals expression signatures related to the EGFR pathway (2005)

Background: Lung cancer is a leading cause of cancer morbidity and mortality worldwide related to advanced staging at the time of presentation or diagnosis. Epidermal Growth Factor Receptor (EGFR) with activating mutations is a potential new molecular therapeutic target responsive to tyrosine kinase inhibitor therapy. Our hypothesis is that there are differential expression gene signatures between lung adenocarcinomas with or without EGFR mutation Methods: Total RNA from 49 resected primary lung adenocarcinomas were analyzed individually for their expression profiles by Affymetrix GeneChip HG-U133 set according to standard protocols. EGFR mutations at exons 18-21 were evaluated by sequencing of cDNA. Expression data were analyzed with publicly available software packages for microarray analysis. Results: 29 tumors showed EGFR mutations (23/32 women, 6/17 men). The mutant cases were significantly associated with life time never smokers (26/32) compared to current or previous smokers. After data normalization across all cases and exclusion of genes showing significant proportion of absent call and genes showing low variance, differential gene expression was compared between tumors with or without EGFR mutations using log transformed signal intensities and two sample t-tests, yielding 318 genes that showed significantly (p&lt;=0.01) higher or lower expression by two fold difference between groups. Hierarchical clustering aiming at detection of co-regulated or co-expressed genes showed significant sample clustering including groups that contained predominantly tumors with or without EGFR mutation. Molecular classification was done with Support Vector Machine with Leave-one out analysis and the Machine Learning Performance was 96% sensitivity and 80% specificity in the prediction of tumours with EGFR mutation. Some examples of differentially expressed genes and molecular classifiers included EGFR, FGFR3, EREG, WIF3, INHBA and TNFSF10. Conclusion: We have identified differentially-expressed and class-predictive genes in primary lung adenocarcinomas with respect to EGFR gene mutation status at exons 18-21. These genes are potentially involved in the EGFR oncogenic pathway and serve as putative diagnostic or therapeutic targets in the management of lung cancer. (Supported by HKSAR RGC grants 7310/01M, 7486/03M, 7468/04M)
Participation of p53 protein in the cellular response to DNA damage. (1991)

The inhibition of replicative DNA synthesis that follows DNA damage may be critical for avoiding genetic lesions that could contribute to cellular transformation. Exposure of ML-1 myeloblastic leukemia cells to nonlethal doses of the DNA damaging agents, gamma-irradiation or actinomycin D, causes a transient inhibition of replicative DNA synthesis via both G1 and G2 arrests. Levels of p53 protein in ML-1 cells and in proliferating normal bone marrow myeloid progenitor cells increase and decrease in temporal association with the G1 arrest. In contrast, the S-phase arrest of ML-1 cells caused by exposure to the anti-metabolite, cytosine arabinoside, which does not directly damage DNA, is not associated with a significant change in p53 protein levels. Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma-irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Unlike ML-1 cells and normal bone marrow myeloid progenitor cells, hematopoietic cells that either lack p53 gene expression or overexpress a mutant form of the p53 gene do not exhibit a G1 arrest after gamma-irradiation; however, the G2 arrest is unaffected by the status of the p53 gene. These results suggest a role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage and thus suggest a new mechanism for how the loss of wild-type p53 might contribute to tumorigenesis.
In vivo T-cell ablation by a holo-immunotoxin directed at human CD3. (1992)

We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immunotoxin constructed with a diphtheria toxin binding-site mutant. Eighty percent of established human T-cell subcutaneous tumors in nude mice completely regressed following intraperitoneal injection of immunotoxin at a dose set at half the minimum lethal dose assayed in toxin-sensitive animals. Similar regressions produced by a 137Cs source required a dose in excess of 500 cGy. The high degree of in vivo T-cell ablation produced by this immunotoxin is apparently due to maintenance of the toxin translocation function provided by CRM9 and a necessary intracellular routing function supplied by CD3. This immunotoxin may be useful in treating conditions caused by pathologic oligoclonal T-cell expansion such as graft-versus-host disease, autoimmune diseases, and possibly AIDS.
Epigenetic regulation of theINK4b-ARF-INK4alocus (2010)

The INK4b-ARF-INK4a locus encodes for two cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a) and a regulator of the p53 pathway, ARF. In addition ANRIL, a non-coding RNA, is also transcribed from the locus. ARF, p15(INK4b) and p16(INK4a) are well-established tumor suppressors which function is frequently disabled in human cancers. Recent studies showed that single nucleotide polymorphisms mapping in the vicinity of ANRIL are linked to a wide spectrum of conditions, including cardiovascular disease, ischemic stroke, type 2 diabetes, frailty and Alzheimer's disease. The INK4b-ARF-INK4a locus is regulated by Polycomb repressive complexes (PRCs), and its expression can be invoked by activating signals. Other epigenetic modifiers such as the histone demethylases JMJD3 and JHDM1B, the SWI/SNF chromatin remodeling complex and DNA methyltransferases regulate the locus interplaying with PRCs. In view of the intimate involvement of the INK4b-ARF-INK4a locus on disease, to understand its regulation is the first step for manipulate it to therapeutic benefit.
Modifying the sugar icing on the transplantation cake (2016)

As a transplant surgeon, my interest in glycobiology began through my research into ABO-incompatible allotransplantation, and grew when my goal became overcoming the shortage of organs from deceased human donors by the transplantation of pig organs into patients with terminal organ failure (xenotransplantation/cross-species transplantation). The major target for human "natural" (preformed) anti-pig antibodies is galactose-α(1,3)-galactose (the "Gal" epitope), which is expressed on many pig cells, including the vascular endothelium. The binding of human IgM and IgG antibodies to Gal antigens initiates the process of hyperacute rejection, resulting in destruction of the pig graft within minutes or hours. This major barrier has been overcome by the production of pigs in which the gene for the enzyme α(1,3)-galactosyltransferase (GT) has been deleted by genetic engineering, resulting in GT knockout (GTKO) pigs. The two other known carbohydrate antigenic targets on pig cells for human anti-pig antibodies are (i) the product of the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene, i.e., N-glycolylneuraminic acid, and (ii) the product of the β1,4 N-acetylgalactosaminyltransferase gene, i.e., the Sd(a) antigen. Expression of these two has also been deleted in pigs. These genetic manipulations, together with others directed to overcoming primate complement and coagulation activation (the latter of which also relates to glycobiology) have contributed to the prolongation of pig graft survival in nonhuman primate recipients to many months rather than a few minutes. Clinical trials of the transplantation of pig cells are already underway and transplantation of pig organs may be expected within the relatively near future.
In Vitro Effect of Ultrasound on Bacteria and Suggested Protocol for Sonication and Diagnosis of Prosthetic Infections (2009)

Sonication of implants has been shown to be a promising method for diagnosis of prosthetic infections due to its improved sensitivity, simplicity, and low cost. The aim of the present study was to evaluate the effects of ultrasound performed under different conditions regarding temperature, duration, and composition of sonication tubes on bacterial species often associated with prosthetic infections. We found that ultrasound had an inhibitory effect on bacteria, of which gram-negative bacteria, in particular Escherichia coli, were almost eradicated after 5 min of sonication at 35 degrees C. Gram-positive bacteria were found to be resistant to the effect of ultrasound. Four factors were important for the inhibitory effect of sonication: the type of microorganism, the temperature of the sonication buffer, the duration of exposure to ultrasound (minutes), and the material and composition of the sonication tube in which sonication is performed. On the basis of the results from the present study, we propose a protocol for sonication and recovery of bacteria associated with biofilm on infected implants prior to conventional culture. From the present protocol, we recommend sonication for 7 min at 22 degrees C at the maximum effect which permits survival of gram-negative bacteria.
Drug Diffusion through Cystic Fibrotic Mucus: Steady-State Permeation, Rheologic Properties, and Glycoprotein Morphology (1996)

One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, isoniazid, and pyrazinamide through unpurified CF respiratory mucus and through purified pig gastric mucus solutions were compared in order to evaluate the relative barrier properties of these mucus solutions. These model compounds, while not often used clinically in CF, are used in other pulmonary diseases and have the potential to be administered by inhalation delivery systems. Permeability studies were carried out in Side-Bi-Side diffusion cells fitted with a custom membrane holder capable of retaining the mucus solutions. Permeabilities through CF mucus solution and its fractions were compared to those measured through buffer and reconstituted purified pig gastric mucus. There were 28--75% decreases in drug permeability when pig gastric mucus was replaced by different CF mucus solutions. This indicates that optimal drug delivery directly to the lungs must take into account the decreased drug transport rate across diseased mucus in addition to drug loss due to binding to the glycoproteins or inefficient delivery via aerosolization. Transmission electron microscopy revealed minor differences in the glycoprotein strand structure between reconstituted pig gastric mucus and CF mucus primarily with regard to glycoprotein chain length and extent of branching. Similar viscoelastic behaviors between the CF gel fraction and synthetic CF mucus were observed. This model CF mucus system can simulate diseased mucus and can be utilized for in vitro studies to optimize drug permeability.
Synthetic topiary (1994)

The paper extends Lindenmayer systems in a manner suitable for simulating the interaction between a developing plant and its environment. The formalism is illustrated by modeling the response of trees to pruning, which yields synthetic images of sculptured plants found in topiary gardens.
Incremental finite-state parsing (1997)

This paper describes a new finite-state shallow parser. It merges constructive and reductionist approaches within a highly modular architecture. Syntactic information is added at the sentence level in an incremental way, depending on the contextual information available at a given stage. This approach overcomes the inefficiency of previous fully reductionist constraint-based systems, while maintaining broad coverage and linguistic granularity. The implementation relies on a sequence of networks built with the replace operator. Given the high level of modularity, the core grammar is easily augmented with corpus-specific sub-grammars. The current system is implemented for French and is being expanded to new languages.
Phenotypic Correction of Diabetic Mice by Adenovirus-Mediated Glucokinase Expression (2001)

Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. GK levels are lowered in patients with maturity-onset diabetes of the young and in some diabetic animal models. Here, we explored the adenoviral vector-mediated overexpression of GK in a diet-induced murine model of type 2 diabetes as a treatment for diabetes. Diabetic mice were treated by intravenous administration with an E1/E2a/E3-deleted adenoviral vector encoding human hepatic GK (Av3hGK). Two weeks posttreatment, the Av3hGK-treated diabetic mice displayed normalized fasting blood glucose levels (95 +/- 4.8 mg/dl; P < 0.001) when compared with Av3Null (135 +/- 5.9 mg/dl), an analogous vector lacking a transgene, and vehicle-treated diabetic mice (134 +/- 8 mg/dl). GK treatment also resulted in lowered insulin levels (632 +/- 399 pg/ml; P < 0.01) compared with the control groups (Av3Null, 1,803 +/- 291 pg/ml; vehicle, 1,861 +/- 392 pg/ml), and the glucose tolerance of the Av3hGK-treated diabetic mice was normalized. No significant increase in plasma or hepatic triglycerides, or plasma free fatty acids was observed in the Av3hGK-treated mice. These data suggest that overexpression of GK may have a therapeutic potential for the treatment of type 2 diabetes.
High-throughput functional annotation of influenza A virus genome at single-nucleotide resolution (2014)

Abstract A novel genome-wide genetics platform is presented in this study, which permits functional interrogation of all point mutations across a viral genome in parallel. Here we generated the first fitness profile of individual point mutations across the influenza virus genome. Critical residues on the viral genome were systematically identified, which provided a collection of subdomain data informative for structure-function studies and for effective rational drug and vaccine design. Our data was consistent with known, well-characterized structural features. In addition, we have achieved a validation rate of 68% for severely attenuated mutations and 94% for neutral mutations. The approach described in this study is applicable to other viral or microbial genomes where a means of genetic manipulation is available.
BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009 (2008)

The BRENDA (BRaunschweig ENzyme DAtabase) (http://www.brenda-enzymes.org) represents the largest freely available information system containing a huge amount of biochemical and molecular information on all classified enzymes as well as software tools for querying the database and calculating molecular properties. The database covers information on classification and nomenclature, reaction and specificity, functional parameters, occurrence, enzyme structure and stability, mutants and enzyme engineering, preparation and isolation, the application of enzymes, and ligand-related data. The data in BRENDA are manually curated from more than 79,000 primary literature references. Each entry is clearly linked to a literature reference, the origin organism and, where available, to the protein sequence of the enzyme protein. A new search option provides the access to protein-specific data. FRENDA (Full Reference ENzyme DAta) and AMENDA (Automatic Mining of ENzyme DAta) are additional databases created by continuously improved text-mining procedures. These databases ought to provide a complete survey on enzyme data of the literature collection of PubMed. The web service via a SOAP (Simple Object Access Protocol) interface for access to the BRENDA data has been further enhanced.
Role of Rac-GTPase and Reactive Oxygen Species in Cardiac Differentiation of Stem Cells (2005)

In the life of a cell, there is a constant balance between generation of reactive oxygen species (ROS) and activity of antioxidant defense mechanisms. Besides the damaging effects of ROS on many biomolecules, ROS also play a significant role in signal transduction pathways of growth factors suggesting a role of oxidative species in cell differentiation. ROS have recently been involved in the process of cardiac differentiation of stem cells. Several molecular mechanisms, including ones mediated by the GTPase Rac that underlie the regulatory role of ROS in the process of stem cell differentiation toward a cardiac lineage, are reviewed.
Mass spectrometric analysis of glycans in elucidating the pathogenesis of CDG type IIx (2003)

The majority of secreted or membrane-bound proteins are glycosylated. The glycans attached to glycoproteins can affect a range of physicochemical and biological properties of the glycoprotein and appropriate glycosylation is essential for many normal cellular functions, with aberrant glycosylation often leading to disease. This short review briefly outlines the methodology used to release glycans from proteins and analyse them by mass spectrometry. The technology is illustrated by the description of a rapid and sensitive method for profiling glycoproteins of patients with congenital disorders of glycosylation type II. This methodology can rapidly pinpoint the defective step(s) in the processing pathway of N-linked glycans, thereby focusing the biochemical analyses that need to be performed to define the genetic basis of these diseases.
Gattermann reaction of 3,5-dimethoxyphenylacetonitrile. Synthesis of 6,8-dioxyisoquinolines (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGattermann reaction of 3,5-dimethoxyphenylacetonitrile. Synthesis of 6,8-dioxyisoquinolinesJames David White and D. S. StrausCite this: J. Org. Chem. 1967, 32, 9, 2689–2692Publication Date (Print):September 1, 1967Publication History Published online1 May 2002Published inissue 1 September 1967https://pubs.acs.org/doi/10.1021/jo01284a009https://doi.org/10.1021/jo01284a009research-articleACS PublicationsRequest reuse permissionsArticle Views203Altmetric-Citations8LEARN 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