gebhart/patrepeval huggingface dataset:
Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF‐R1‐Flt1 and VEGF‐R2‐Flk1/KDR) in non‐small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival (1999)

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I–II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0·018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0·0001) and VEGF-R2 ( p = 0·0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0·0001) and VEGF-R2 ( p = 0·04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0·0028) and VEGF-R2 ( p = 0·01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I–II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC. Copyright © 1999 John Wiley & Sons, Ltd.
Field Application of Lignosulfonate Gels to Reduce Channeling, South Swan Hills Miscible Unit, Alberta, Canada (1986)

ABSTRACT Following initiation by Amoco in 1973 of a secondary miscible (WAG) flood in the South Swan Hills Unit, tracer performance indicated severe channeling of solvent and water, particularly in the northwest quarter of the Unit. In 1975 and 1977, problem zones at 9 injectors were isolated and selectively treated with chrome-lignosulfonate time-set gels in an attempt to reduce solvent and water cycling. The treatment volumes varied between 8500 and 14,000 bb1s (1350 and 2225 m3) per well. As part of an evaluation of the gel treatments, incremental oil production responses observed at a number of the 56 producers offset to the 9 treated injectors were examined. The responses which could not be explained by other contributory factors, such as the drilling of infill seam injection wells, well workovers (e.g. acid jobs and asphaltene treatments), casing repairs, and pump changeouts, were considered to be the result of improved sweep due to the gel treatments. Thirteen of the 56 offset producers (23%) were found to have responded to the gel treatments, and these were rated as to the duration of response. Response durations of up to 18 months were rated as "good," and those lasting longer were rated as "excellent." Although a detailed economic analysis was not performed, a comparison of the total cost of the 9 injector gel treatments with the gross revenues generated by the total calculated incremental oil from the 13 responding producers indicates that the treatments were an economic success.
T-bet is required for optimal proinflammatory CD4+ T-cell trafficking (2005)

Inflammatory responses are controlled by T helper 1 (Th1) lymphocytes. An important function of this polarity is the ability of T cells to traffick appropriately in vivo. This differential trafficking is dependent upon the binding of P-selectin glycoprotein ligand-1 to P- and E-selectin on inflamed endothelium as well as the expression of specific chemokine receptors. Here we show that in the absence of T-box expressed in T cells (T-bet), selective migration of T cells in vivo is completely abrogated and that T-bet regulates the binding of CD4(+) T cells to P-selectin. T-bet is also required for the expression of the chemokine receptor CXCR3. Thus, T-bet controls Th1-cell migration to inflammatory sites, which has fundamental consequences for the control of immunologic disease.
Immunosuppression with FTY720 is insufficient to prevent secondary progressive neurodegeneration in experimental autoimmune encephalomyelitis (2011)

This study indicates that early intervention with immunosuppressive agents may inhibit the generation of the neurodegenerative microenvironment, which is no longer responsive to potent immunosuppression. However, if treatment is initiated too late, progressive, neurological-disease continues unabated. This suggests that immunosuppression is insufficient to control secondary progression in animals, as has been found so far to be the case in MS, and may warrant early intervention with FTY720 for optimal treatment benefit.
Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation (2015)

De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusing mechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.
Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning (2021)

Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P<0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P<0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P<0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P<0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.
[Chronic sacral bilateral neuromodulation. Using a minimal invasive implantation technique in patients with disorders of bladder function]. (2002)

The implantable neuromodulation system described by Tanagho and Schmidt enables unilateral sacral nerve stimulation. Reports have been made on sacral neuromodulation failures of up to 50% in patients undergoing this procedure. We chose the bilateral electrode implantation and a minimal invasive laminectomy to ensure a more effective modulation and better placement and fixation of the electrodes. After successful assessment using a peripheral nerve evaluation test, 20 patients (14 with detrusor instability, 6 with hypocontractile detrusor) underwent minimally invasive laminectomy and bilateral electrode placement. In the patients with detrusor instability, the incontinence episodes were reduced from 7.2 to 1 per day and the bladder capacity improved from 198 to 352 ml. In patients with hypocontractile detrusor, the initial residual urine level of 450 ml dropped to 108 ml. Maximum detrusor pressure during micturition rose from 12 cmH2O initially to 34 cmH2O. The average follow up period was 17.5 months. There was no sign of deterioration in the modulation effect in any of the patients. Bilateral electrode implantation and the new sacral approach allow optimal neuromodulation in patients with bladder dysfunction. Laminectomy enables optimum electrode placement and fixation with minimal trauma.
A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon. (1992)

We previously established that the expression of a thymic c-myb mRNA species requires the intermolecular recombination of coding sequences expressed from transcriptional units localized on different chromosomes, in both chicken and human. We now report that a putative splicing factor (PR264), extremely well conserved in chicken and human, is encoded by the opposite strand of the c-myb trans-spliced exon. The PR264 polypeptide, which contains a typical ribonucleoprotein 80 and an arginine/serine-rich domain, is highly homologous to the Drosophila splicing regulators tra, tra-2, and su(wa) and to the human alternative splicing factor ASF/SF2. Furthermore, we show that PR264-specific mRNAs are expressed in normal hematopoietic cells of chicken and human origin and that the relative proportion of the PR264 transcripts is developmentally regulated in chicken.
Massively Parallel Parsing: A Strongly Interactive Model of Natural Language Interpretation* (1985)

This is a description of research in developing a natural language processing system with modular knowledge sources but strongly interactive processing. The system offers insights into a variety of linguistic phenomena and allows easy testing of a variety of hypotheses. Language interpretation takes place on a activation network which is dynamically created from input, recent context, and long‐term knowledge. Initially ambiguous and unstable, the network settles on a single interpretation, using a parallel, analog relaxation process. We also describe a parallel model for the representation of context and of the priming of concepts. Examples illustrating contextual influence on meaning interpretation and “semantic garden path” sentence processing, among other issues, are included.
Purification and Properties of Bacterial Chondroitinases and Chondrosulfatases (1968)

Abstract 1. An enzyme, has been purified to apparent homogeneity from extracts of Proteus vulgaris, NCTC 4636, which was adapted on a medium containing chondroitin sulfate C. It has the following properties. (a) At pH 8, it degrades chondroitin sulfates A, B, and C at greater rates than chondroitin and hyaluronic acid. It does not attack keratosulfate, heparin, or heparitin sulfate. (b) It carries out an elimination reaction, yielding Δ4,5-unsaturated disaccharides. (c) In the crude extract it is accompanied by two different types of sulfatase, which are removed during purification. 2. The two sulfatases, chondro-4-sulfatase and chondro-6-sulfatase, have been separated from chondroitinase-ABC and from each other; both are required for the hydrolytic desulfation of chondroitinase products, Δ4,5-unsaturated disaccharide sulfates. They do not attack polymer chondroitin sulfates, hexa-, penta-, tetra-, or trisaccharides derived from chondroitin sulfates A and C by digestion with crude testicular hyaluronidase, or acetylgalactosamine 4-and 6-sulfates. One of these enzymes, chondro-4-sulfatase, catalyzes the conversion of Δ4,5-unsaturated disaccharide 4-sulfate (i.e. the product from the degradation of chondroitin sulfate A or B by chondroitinase-ABC) and its saturated analogue (i.e. acetylchondrosin 4-sulfate) to the corresponding nonsulfated disaccharides and inorganic sulfate, but does not attack Δ4,5-unsaturated disaccharide 6-sulfate (i.e. the product from the degradation of chondroitin sulfate C by chondroitinase-ABC) or its saturated analogue (i.e. acetylchondrosin 6-sulfate). In contrast, chondro-6-sulfatase carries out the desulfation of the disaccharide 6-sulfates and acetylgalactosamine 4,6-disulfate at position 6 while it does not attack the disaccharide 4-sulfate isomers. 3. Another type of chondroitinase, chondroitinase-AC, has been purified also to apparent homogeneity from extracts of Flavobacterium heparinum, ATCC 13125, which was adapted on a medium containing chondroitin sulfate C. Its properties have been compared with those of chondroitinase-ABC from P. vulgaris. (a) Unlike chondroitinase-ABC, it has no measurable activity with chondroitin sulfate B; like chondroitinase-ABC it carries out essentially the same reactions with chondroitin sulfates A and C, chondroitin, and hyaluronic acid. (b) In the crude extract it is accompanied by an enzyme similar to chondroitinase-ABC, an enzyme similar to chondro-4-sulfatase, and a glucuronidase which hydrolyzes the β-glucuronidic bond of unsaturated disaccharides but not the bond of saturated disaccharides. All these accompanying enzymes are removed during purification.
Sequential Immunization With Live-Attenuated Chimeric Hemagglutinin-Based Vaccines Confers Heterosubtypic Immunity Against Influenza A Viruses in a Preclinical Ferret Model (2019)

Due to continuous antigenic drift and occasional antigenic shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity and mortality in humans. Therefore, to avoid the need for annual reformulation and readministration of seasonal influenza virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccine, which is comprised of sequential immunization with antigens containing a conserved stalk domain derived from a circulating pandemic H1N1 strain in combination with "exotic" head domains. Here, we show that this prime-boost sequential immunization strategy redirects antibody responses toward the conserved stalk region. We compared the vaccine efficacy elicited by distinct vaccination approaches in the preclinical ferret model of influenza. All ferrets immunized with cHA-based vaccines developed stalk-specific and broadly cross-reactive antibody responses. Two consecutive vaccinations with live-attenuated influenza viruses (LAIV-LAIV) conferred superior protection against pH1N1 and H6N1 challenge infection. Sequential immunization with LAIV followed by inactivated influenza vaccine (LAIV-IIV regimen) also induced robust antibody responses. Importantly, the LAIV-LAIV immunization regimen also induced HA stalk-specific CD4<sup>+</sup>IFN-γ<sup>+</sup> and CD8<sup>+</sup>IFN-γ<sup>+</sup> effector T cell responses in peripheral blood that were recalled by pH1N1 viral challenge. The findings from this preclinical study suggest that an LAIV-LAIV vaccination regimen would be more efficient in providing broadly protective immunity against influenza virus infection as compared to other approaches tested here.
Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV (2020)

Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
Human ErbB-2 (Her-2) Transgenic Mice: A Model System for Testing Her-2 Based Vaccines (2003)

Her-2 transgenic (Tg) mice were generated with wild-type human c-ErbB-2 (Her-2) under the whey acidic protein promoter. They are tolerant to Her-2 and appropriate for testing Her-2 vaccines. The expression of transmembrane ErbB-2 from the whey acidic protein-Her-2 cassette and its up-regulation by insulin and hydrocortisone was verified by in vitro transfection. The transgene cassette was microinjected into fertilized eggs from B6C3 (C3H x C57BL/6) females mated with B6C3 males. Transgene-positive mice were backcrossed onto C57BL/6 mice. Human ErbB-2 was expressed in the secretory mammary epithelia during pregnancy and lactation and expressed constitutively in the Bergman glia cells within the molecular layer of the cerebellum. Overt, neoplastic transformation was not detected in any tissue examined. Tolerance to Her-2 was demonstrated by inoculating mice with a syngenic tumor expressing high levels of human ErbB-2. Tumors grew exclusively in Her-2 Tg mice without inducing an Ab response, while the nontransgenic littermates remained tumor free for 10 mo and mounted a robust anti-ErbB-2 Ab response. When immunized five times with plasmid DNA encoding secErbB-2 and GM-CSF, respectively, approximately 33% of the Her-2 Tg mice rejected a lethal challenge of EL-4/E2 tumor cells, whereas all immunized littermates rejected the tumor. Therefore, Her-2 Tg mice express human ErbB-2 in the brain and mammary gland and demonstrated tolerance to ErbB-2 which was partially overcome by DNA vaccination. The breakable tolerance of Her-2 Tg mice resembles that in human and these mice are particularly suited for testing human ErbB-2 based vaccines.
Useful diene for the Diels-Alder reaction (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUseful diene for the Diels-Alder reactionS. Danishefsky and T. KitaharaCite this: J. Am. Chem. Soc. 1974, 96, 25, 7807–7808Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://doi.org/10.1021/ja00832a031Request reuse permissionsArticle Views8809Altmetric-Citations419LEARN 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 InReddit PDF (282 KB) Get e-Alertsclose Get e-Alerts
Ceftazidime, gentamicin, and rifampicin, in combination, kill biofilms of mucoidPseudomonas aeruginosa (1997)

In continuous flow biofilm cultures in medium resembling cystic fibrosis bronchial secretions, Pseudomonas aeruginosa was not eradicated from biofilms by 1 week of treatment with high concentrations of ceftazidime and gentamicin, to which the strains were sensitive on conventional testing. The addition of rifampicin, which has little activity against the strains as measured by the minimum inhibitory concentration, led to the apparent elimination of the bacteria from the biofilms. The effect was not strain specific.
Killing the messenger: new insights into nonsense-mediated mRNA decay (2002)

A When the accession numbers are entered at the National Center for Biotechnology Information home site (http://www.ncbi.nlm.nih.gov/)they will provide direct links to nucleotide and protein sequences as well as references to the identification of these genes.B UPF3B (XM_016123) and UPF3X (NM_023010) appear to represent two additional copies of the UPF3 gene.How they differ in function from the UPF3A gene and transcript is not understood.C The web address for WormBase, the database for C. elegans genome information, is http://www.wormbase.org/.EST, expressed sequence tag.
Enhancements to the RADAR User Location and Tracking System (2000)

Recent developments in neurobiology, diagnostic classification, and drug/psychotherapy trials have increased our ability to manage patients with anxiety disorders. These recent developments, along with epidemiologic surveys showing the high frequency of anxiety disorders in the general population as well as in the primary care population, have reemphasized the importance of anxiety disorders in family practice. This review presents treatment recommendations, including dosage, products, guidelines for monitoring, and discontinuation. Advances in the neurobiology of anxiety are also included.
Transcriptome and proteome responses in RNAlater preserved tissue of Arabidopsis thaliana (2017)

Tissue preservation is a minimal requirement for the success of plant RNA and protein expression studies. The standard of snap-freezing in liquid nitrogen is not always practical or possible. RNAlater, a concentrated solution of ammonium and cesium sulfates, has become a standard preservative in the absence of liquid nitrogen. Here, we demonstrate the effectiveness of RNAlater in preserving both RNA and proteins in Arabidopsis thaliana tissues for use in RNAseq and LC-MS/MS analysis of proteins. While successful in preserving plant material, a transcriptomic and proteomic response is evident. Specifically, 5770 gene transcripts, 84 soluble proteins, and 120 membrane-bound proteins were found to be differentially expressed at a log-fold change of ±1 (P ≤ 0.05). This response is mirrored in the abundance of post-translational modifications, with 23 of the 108 (21.3%) phosphorylated proteins showing altered abundance at a log-fold change of ±1 (P ≤ 0.05). While RNAlater is effective in preserving biological information, our findings warrant caution in its use for transcriptomic and proteomic experiments.