gebhart/patrepeval huggingface dataset:
Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis (2013)

Patients suffering from cardiovascular disease have well-established atherosclerotic lesions, rendering lesion regression of therapeutic interest. The OX40 (TNFRSF4)-OX40 ligand (OX40L; TNFSF4) pathway is important for the proliferation and survival of T cells, stimulates B cells, and is associated with cardiovascular disease. We hypothesized that interference with the OX40-OX40L pathway, in combination with decreases in cholesterol, may induce regression of atherosclerosis. LDLr(-/-) mice were fed a Western-type diet for 10 wk, after which they received chow diet and were treated with anti-OX40L or PBS for 10 wk. A significant regression of lesions was observed in the aorta and aortic arch of anti-OX40L-treated mice compared with control mice. Interference of the OX40-OX40L pathway reduced Th2 responses, as shown by decreases in GATA-3 and IL-4 levels. Also, IgE levels were decreased, as demonstrated by reduced mast cell presence and activation. Notably, IL-5 production by T and B1 cells was increased, thus enhancing atheroprotective oxidized low-density lipoprotein-specific IgM production. The increase in IL-5 production and IgM was mediated by IL-33 production by APCs upon OX40L blockade. We conclude that interruption of the OX40-OX40L signaling pathway, combined with decreases in dietary cholesterol, induces the regression of atherosclerosis through induction of IL-5-producing T cells and oxidized low-density lipoprotein-specific IgM and reductions in Th2 and mast cells.
Breast Cancer in Vivo: Contrast Enhancement with Thermoacoustic CT at 434 MHz—Feasibility Study (2000)

The authors performed thermoacoustic computed tomography (CT) with 434-MHz radio waves in five patients with documented breast cancer. Three of the patients underwent imaging before chemotherapy was initiated and two at the conclusion of their primary chemotherapy. In the former three patients, thermoacoustic CT demonstrated contrast enhancement in the region of the tumor. In the latter two patients, no contrast enhancement was seen, and pathologic examination after surgical resection of the area of original tumor confirmed complete remission of disease.
The Color of the Sky (2012)

The color of the sky in day-time and at twilight is studied by means of spectroscopy, which provides an unambiguous way to understand and quantify why a sky is blue, pink, or red. The colors a daylight sky can take primarily owe to Rayleigh extinction and ozone absorption. Spectra of the sky illuminated by the sun can generally be represented by a generic analytical expression which involves the Rayleigh function , ozone absorption, and, to a lesser extend, aerosol extinction. This study is based on a representative sample of spectra selected from a few hundred observations taken in different places, times, and dates, with a portable fiber spectrometer.
Robust stepwise regression (2002)

The selection of an appropriate subset of explanatory variables to use in a linear regression model is an important aspect of a statistical analysis. Classical stepwise regression is often used with this aim but it could be invalidated by a few outlying observations. In this paper, we introduce a robust F-test and a robust stepwise regression procedure based on weighted likelihood in order to achieve robustness against the presence of outliers. The introduced methodology is asymptotically equivalent to the classical one when no contamination is present. Some examples and simulation are presented.
A General Method for Making Peptide Therapeutics Resistant to Serine Protease Degradation: Application to Dipeptidyl Peptidase IV Substrates (2013)

Bioactive peptides have evolved to optimally fulfill specific biological functions, a fact which has long attracted attention for their use as therapeutic agents. While there have been some recent commercial successes fostered in part by advances in large-scale peptide synthesis, development of peptides as therapeutic agents has been significantly impeded by their inherent susceptibility to protease degradation in the bloodstream. Here we report that incorporation of specially designed amino acid analogues at the P1' position, directly C-terminal of the enzyme cleavage site, renders peptides, including glucagon-like peptide-1 (7-36) amide (GLP-1) and six other examples, highly resistant to serine protease degradation without significant alteration of their biological activity. We demonstrate the applicability of the method to a variety of proteases, including dipeptidyl peptidase IV (DPP IV), dipeptidyl peptidase 8 (DPP8), fibroblast activation protein α (FAPα), α-lytic protease (αLP), trypsin, and chymotrypsin. In summary, the "P1' modification" represents a simple, general, and highly adaptable method of generating enzymatically stable peptide-based therapeutics.
Signaling System in Porphyromonas gingivalis Based on a LuxS Protein (2001)

The luxS gene of quorum-sensing Vibrio harveyi is required for type 2 autoinducer production. We identified a Porphyromonas gingivalis open reading frame encoding a predicted peptide of 161 aa that shares 29% identity with the amino acid sequence of the LuxS protein of V. harveyi. Conditioned medium from a late-log-phase P. gingivalis culture induced the luciferase operon of V. harveyi, but that from a luxS insertional mutant did not. In P. gingivalis, the expression of luxS mRNA was environmentally controlled and varied according to the cell density and the osmolarity of the culture medium. In addition, differential display PCR showed that the inactivation of P. gingivalis luxS resulted in up-regulation of a hemin acquisition protein and an arginine-specific protease and reduced expression of a hemin-regulated protein, a TonB homologue, and an excinuclease. The data suggest that the luxS gene in P. gingivalis may function to control the expression of genes involved in the acquisition of hemin.
Regulation of MyoD gene transcription and protein function by the transforming domains of the adenovirus E1A oncoprotein. (1993)

It has been demonstrated that the adenovirus E1A gene products inhibit myogenic differentiation in the mouse C2 muscle cell line. During myogenic differentiation, cell growth and tissue-specific gene expression are mutually exclusive. Since E1A exerts multiple effects on different cellular pathways through alteration of cell growth control and transcriptional regulation, we investigated in more detail the molecular mechanisms underlying the inhibitory effect of E1A on myogenic differentiation. To this end, we used mutant derivatives of E1A that lack the 'conserved domain' sequences to which the functional domains of E1A have been mapped, and we observed the effect of constitutive expression of these E1A mutants on myogenesis in the murine C2 muscle cell line. Our results demonstrate that E1A interferes with myogenesis through at least two mechanisms: (i) the inhibition of MyoD expression; (ii) the repression of MyoD-dependent transcriptional activation. In addition, we demonstrate also that the repression of MyoD transcription depends upon sequences located in the N-terminus of E1A and correlates well with the site of E1A/p300 association. Further, the inhibition of transcriptional activation by MyoD depends both on conserved region 1 and on conserved region 2, the two transforming domains of E1A. We demonstrate also that a similar inhibitory effect on the MyoD transactivating function is provided by the polyomavirus and SV40 large T oncoproteins.
Photopheresis: a Clinically Relevant Immunobiologic Response Modifier (1991)

Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is an effective new treatment for certain disorders caused by aberrant T lymphocytes. It has become a standard therapy for advanced cutaneous T cell lymphoma and shows promise in the treatment of four autoimmune disorders (pemphigus vulgaris, the progressive systemic sclerosis form of scleroderma, rheumatoid arthritis, systemic lupus erythematosus) and in reversal of immunologic rejection of transplanted organs. Positive immunologic alterations observed in patients with AIDS-related complex merit further investigation, and preliminary trials in the management of patients with multiple sclerosis, myasthenia gravis and autoimmune insulin-dependent diabetes mellitus have recently been initiated. The inability of the treatment to meaningfully alter the course of the B cell malignancy, chronic lymphocytic leukemia, suggests that B cell proliferations, at least those involving malignant cells, may be more resistant to this treatment. The mechanism of action of photopheresis is likely to be multifaceted, but at least in experimental systems appears to involve an immunization against the pathogenic T cells, in a highly specific manner. Photoactivated 8-MOP initiates a cascade of cellular events by forming covalent photoadducts with nuclear DNA, with cell surface molecules and possibly with other cytoplasmic components of the ultraviolet exposed leukocytes. For reasons not yet clear, exposure of populations of T cells containing expanding a clone(s) of pathogenic T cells to photoactivated 8-MOP alters these cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the same pathogenic clone(s). It is suggested that the specificity of the induced immunologic reaction may result, in sequence, from the exquisitely titratable damage that 8-MOP inflicts upon cells of the pathogenic clone(s), the return of these cells to an immunocompetent individual, the removal of the photo-damaged cells from the blood by the reticuloendothelial system and the preferential induction of an immune response against cells of the pathologically expanded clone(s).
Evaluation of the immunogenicity of protein hydrolysate formulas using laboratory animal hyperimmunization (1994)

The rabbit hyperimmunization model has previously been used to evaluate candidate hypoallergenic protein ingredients. Use of the model has been expanded to include the evaluation of protein hydrolysate formulas. Each formula's immunological reactivity was determined by ELISA measurement of formula-specific rabbit antibody. Animals hyperimmunized with formulas containing extensively hydrolyzed proteins (Alimentum, Nutramigen, and Pregestimil) generated very weak immune responses (< 100 fold antibody increase). Products containing intact or partially hydrolyzed proteins (Similac, Enfamil, Good Start, Beba HA, and Nidina HA) elicited high level (> 10,000 fold increase) immune responses. Immunogenicity results were then compared to measurements of residual antigen content (by inhibition ELISA) and clinical performance. Correlation of formula immunogenicity, antigenicity and clinical performance indicates that the rabbit model is useful for screening "hypoallergenic" formulas to predict allergenic reactivity.
Blended Acquisition – A potential step-change in geophysical flexibility and operational efficiency (2017)

PreviousNext No Access15th International Congress of the Brazilian Geophysical Society & EXPOGEF, Rio de Janeiro, Brazil, 31 July-3 August 2017Blended Acquisition – A potential step-change in geophysical flexibility and operational efficiencyAuthors: Eivind FromyrEivind FromyrPGShttps://doi.org/10.1190/sbgf2017-151 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Abstract The introduction of additional sources in marine seismic acquisition can lead to more versatile geometries including longer offsets and more diverse azimuth coverage. It also has the potential to make some acquisition templates more efficient and reduce the need for infill as well as reducing the technical risk and HSE exposure. To avoid reduction in fold and shot density the sources can be fired simultaneously. The challenge is to preserve the geophysical integrity of the data, in particular in the pre stack domain, through a robust randomization scheme and subsequent de-blending methodology. Keywords: deblending, offset, acquisitionPermalink: https://doi.org/10.1190/sbgf2017-151FiguresReferencesRelatedDetailsCited byReferences4 February 2021 15th International Congress of the Brazilian Geophysical Society & EXPOGEF, Rio de Janeiro, Brazil, 31 July-3 August 2017ISSN (online):2159-6832Copyright: 2017 Pages: 1876 publication data© 2017 Published in electronic format with permission by the Brazilian Geophysical SocietyPublisher:Society of Exploration Geophysicists HistoryPublished Online: 03 Aug 2017 CITATION INFORMATION Eivind Fromyr, (2017), "Blended Acquisition – A potential step-change in geophysical flexibility and operational efficiency," SEG Global Meeting Abstracts : 768-771. https://doi.org/10.1190/sbgf2017-151 Plain-Language Summary KeywordsdeblendingoffsetacquisitionPDF DownloadLoading ...
Seven evolutionarily conserved human rhodopsin G protein‐coupled receptors lacking close relatives (2003)

We report seven new members of the superfamily of human G protein-coupled receptors (GPCRs) found by searches in the human genome databases, termed GPR100, GPR119, GPR120, GPR135, GPR136, GPR141, and GPR142. We also report 16 orthologues of these receptors in mouse, rat, fugu (pufferfish) and zebrafish. Phylogenetic analysis shows that these are additional members of the family of rhodopsin-type GPCRs. GPR100 shows similarity with the orphan receptor SALPR. Remarkably, the other receptors do not have any close relative among other known human rhodopsin-like GPCRs. Most of these orphan receptors are highly conserved through several vertebrate species and are present in single copies. Analysis of expressed sequence tag (EST) sequences indicated individual expression patterns, such as for GPR135, which was found in a wide variety of tissues including eye, brain, cervix, stomach and testis. Several ESTs for GPR141 were found in marrow and cancer cells, while the other receptors seem to have more restricted expression patterns.
Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation1 (2003)

Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.
Adoptive T-Cell Therapy for EBV-Associated Post-Transplant Lymphoproliferative Disease (2003)

Increased understanding of the mechanisms by which T lymphocytes recognize virus and tumor-specific antigens has fueled the use of adoptive immunotherapy for viral and malignant diseases. An ideal candidate for such treatment is Epstein-Barr virus (EBV). EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication post-solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). The disease is essentially the result of suppression of cytotoxic T-cell function and despite various treatment strategies the course may still be fulminant and lethal. Therefore, an adoptive immunotherapeutic approach using ex vivo derived EBV-specific CTL offers a promising solution not only for the treatment but also as prophylaxis for PTLD. The infusion of EBV-CTL has been demonstrated to be safe and effective in allogeneic HSCT recipients and their use post-SOT is being evaluated.
Yellow Fever/Japanese Encephalitis Chimeric Viruses: Construction and Biological Properties (1999)

A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties when expressed with its prM protein together with the YF capsid; however, viable chimeric viruses incorporating the entire JE structural region (C-prM-E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 10(6) PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than JE-N. Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neurovirulence in this chimeric system. This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.
Long-Term Engraftment and Fetal Globin Induction upon BCL11A Gene Editing in Bone-Marrow-Derived CD34 + Hematopoietic Stem and Progenitor Cells (2017)

To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the <i>BCL11A</i> gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34<sup>+</sup> hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of <i>BCL11A</i> resulting from bi-allelic frameshift mutations in <i>BCL11A</i> exon 2 adversely affected erythroid enucleation. In contrast, bi-allelic disruption of the GATAA motif in the erythroid enhancer of <i>BCL11A</i> did not negatively impact enucleation. Furthermore, <i>BCL11A</i> exon 2-edited BM-CD34<sup>+</sup> cells demonstrated a significantly reduced engraftment potential in immunodeficient mice. Such an adverse effect on HSPC function was not observed upon <i>BCL11A</i> erythroid-enhancer GATAA motif editing, because enhancer-edited CD34<sup>+</sup> cells achieved robust long-term engraftment and gave rise to erythroid cells with elevated levels of fetal globin expression when chimeric BM was cultured ex vivo. Altogether, our results support further clinical development of the <i>BCL11A</i> erythroid-specific enhancer editing in BM-CD34<sup>+</sup> HSPCs as an autologous stem cell therapy in SCD patients.
A Cell Culture Model for T Lymphocyte Clonal Anergy (1990)

T lymphocytes respond to foreign antigens both by producing protein effector molecules known as lymphokines and by multiplying. Complete activation requires two signaling events, one through the antigen-specific receptor and one through the receptor for a costimulatory molecule. In the absence of the latter signal, the T cell makes only a partial response and, more importantly, enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation. Our current understanding at the molecular level of this modulatory process and its relevance to T cell tolerance are reviewed.
[An observation on pathological changes in retinal ultrastructure of rat with hypertension and after its life-long treatment with captopril]. (1995)

The fundus and retinal ultrastructural changes of rats with hypertension and such rats having taken life-long captopril treatment were examined by funduscope, light and transmission electron microscopes. The normal rats were the controls. The results showed that in the hypertension group, the ratio of the diameter of the retinal artery to that of the vein was 1:2, the arteries were spastic and narrowed, their light reflexes were widened and their calibers of the lumens were uneven, the fundus appearances being consistent with grade I and II retinal changes of systemic hypertension. Under the light microscope, it was discovered that the basement membranes of the retinal capillaries were thickened and their lumens narrowed, resulting in retinal ischemia and anoxia. Under the transmission electron microscope, the main pathological changes involved the external segments of photoreceptors and ganglionic cells. The pathological changes were hazy renewed membranous discs at the basal portions of the external segments of photoreceptors, edematous ganglionic cells being the majority, their cytoplasm stained pale, mitochondrial vacuolization, enlargement of smooth endoplasmic reticula and degranulation of rough endoplasmic reticula. In the group of rats with hypertension having taken life-long captopril treatment, the fundi and blood pressure remained normal and no significant ultrastructural changes had taken place in their retinae.
Evaluation of a taxi sector reform: A real options approach (2003)

This paper applies the real options methodology to estimate the impact of the reestruc-turing measures in the taxi sector in Barcelona in 1995. These measures included among other things the establishment of a fixed price for the license as a way to reduce the uncertainty on the future performance of the sector. We construct a model that takes into account the uncertainty in income as well as costs of the taxi driver using both individual and aggregate data. We take into account the option to sell the license at each point in time. We show that such reform can increase the net surplus value for taxi drivers respect to a liberalized market in this sector. We compute the surplus value as a result of this reform to be around C=80.000. This value is shown to be robust to an exhaustive sensitivity analysis.
ChemInform Abstract: Synthesis of Aziridine‐2,2‐dicarboxylates via 1,4‐Addition of N,O‐(Bistrimethylsilyl)hydroxylamine to α,β‐Unsaturated Malonates. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.