gebhart/patrepeval huggingface dataset:
Peptide HER2(776–788) represents a naturally processed broad MHC class II-restricted T cell epitope (2001)

HER2/neu-derived peptides inducing MHC class II-restricted CD4+ T helper lymphocyte (Th) responses, although critical for tumour rejection, are not thoroughly characterized. Here, we report the generation and characterization of CD4+ T cell clones specifically recognizing a HER-2/neu-derived peptide (776-788) [designated HER2(776-788)]. Such clones yielded specific proliferative and cytokine [gamma-interferon(IFN)-gamma] responses when challenged with autologous dendritic cells (DCs) loaded with HER2(776-788). By performing blocking studies with monoclonal antibodies (MAbs) and by using DCs from allogeneic donors sharing certain HLA-DR alleles, we found that HER2(776-788) is a promiscuous peptide presented, at least, by DRB5*0101, DRB1*0701 and DRB1*0405 alleles. One TCRV beta 6.7+ clone recognized the HLA-DRB5*0101+ FM3 melanoma cell line transfected with a full length HER-2/neu cDNA. Moreover, this clone recognized the HER-2/neu+ SKBR3 breast cancer cell line induced to express HLA-DR, thus demonstrating that HER2(776-788) represents a naturally processed and presented epitope. Our data demonstrate that helper peptide HER2(776-788) represents a promiscuous epitope binding to at least three HLA-DR alleles, thus offering a broad population coverage. The use of antigenic peptides presented by major histocompatibility complex (MHC) class II in addition to those presented by class I may improve the therapeutic efficacy of active immunization.
Linked Foreign T-Cell Help Activates Self-Reactive CTL and Inhibits Tumor Growth (2005)

Transgenic mice expressing membrane-bound OVA under the rat insulin promoter, RIP-mOVA, has previously been suggested to display deletional tolerance toward the dominant CTL epitope, SIINFEKL, and provide an elegant model system to test the hypothesis that the lack of T cell help contributes to the tolerance. To understand how the CD8 tolerance is maintained in these mice, a set of neo-self-Ags, OVA, modified to contain a foreign Th peptide, were constructed and tested for their ability to induce CTL responses in RIP-mOVA mice. Immunization with these Th peptide-modified OVA molecules and not with the wild-type OVA induced self-reactive CTLs recognizing dominant CTL peptide, SIINFEKL. Importantly, immunization with the modified OVA constructs also prevented the growth of OVA-expressing tumors in transgenic mice. Since endogenous OVA Th peptides did not contribute toward breaking self CTL tolerance, these results also highlighted a very robust CD4 T cell tolerance toward OVA in RIP-mOVA mice that has not been previously described. These results therefore provide direct evidence that it is the tolerance in the CD4 Th cell compartment that helps maintain the CTL tolerance against self-Ag in these mice. Since the CTL tolerance can be broken or bypassed by foreign Th peptides inserted into a self Ag, potential of using this approach in generating effective therapeutic cancer vaccines is discussed.
Of genes and phenotypes: the immunological and molecular spectrum of combined immune deficiency.Defects of the gc‐JAK3 signaling pathway as a model (2000)

Cytokines play a major role in lymphoid development. Defects of the common gamma chain (gamma(c)) or of the JAK3 protein in humans have been shown to result in a severe combined immune deficiency (SCID), with a profound defect in T and natural killer (NK)-cell development, whereas B-cell generation is apparently unaffected (T-B+NK-SCID). While extensive molecular and biochemical analysis of these patients has been instrumental in understanding better the biological properties of the gamma(c) and JAK3 protein, an unexpected phenotypic heterogeneity of gamma(c) and JAK3 deficiency has emerged, indicating the need for appropriate and extensive investigations even in patients with atypical presentations. At the same time, characterization of the defects has been instrumental in the development of novel therapeutic approaches, from in utero hematopoietic stem cell transplantation to gene therapy.
Optoacoustic image reconstruction: the full inverse problem with variable bases (2018)

Optoacoustic imaging was for a long time concerned with the reconstruction of energy density or optical properties. In this work, we present the full inverse problem with respect to optical absorption and diffusion as well as speed of sound and mass density. The inverse problem is solved by an iterative gradient-based optimization procedure. Since the ill-conditioning increases with the number of sought parameters, we propose two approaches to improve the conditioning. The first approach is based on the reduction of the size of the basis for the parameter spaces, that evolves according to the particular characteristics of the solution, while maintaining the flexibility of element-wise parameter selection. The second approach is a material identification technique that incorporates prior knowledge of expected material types and uses the acoustical gradients to identify materials uniquely. We present numerical studies to illustrate the properties and functional principle of the proposed methods. Significant convergence speed-ups are gained by the two approaches countering ill-conditioning. Additionally, we show results for the reconstruction of a mouse brain from in vivo measurements.
Angiopoietin‐1 is an apoptosis survival factor for endothelial cells (1999)

We examined the effect of angiopoietin‐1 (Ang1) on apoptosis in human umbilical vein endothelial cells (HUVECs). Ang1 (5–1000 ng/ml) dose‐dependently inhibited apoptosis under a serum‐deprived state. A significant apoptotic inhibition occurred with as low as 50 ng/ml. Two hundred ng/ml of Ang1 inhibited to approximately 50% of the control apoptotic rates for 96 h. Furthermore, an augmented antiapoptotic effect of Ang1 by the addition of 20 ng/ml vascular endothelial growth factor was observed. This Ang1‐induced strong antiapoptotic effect in endothelial cells is a novel and intriguing finding and could be an additional description of Ang1‐induced direct biological function.
Algunas consideraciones para lograr una agricultura de regadío sostenible (2017)

"El articulo trata de aquellos aspectos a tener en cuenta bajo los conceptos actuales de desarrollo agrícola sustentable, en el que se considera como un elemento muy importante el papel que desempeña la población local en cualquier decisión vinculada con los proyectos de riego, sus hábitos, costumbres, nivel educacional y cultural, de gestión, así como los recursos naturales autóctonos, los cuales son elementos de vital importancia en la toma de decisiones. Se exponen algunas consideraciones generales en relación a los elementos que se deben tener en cuenta en la elaboración e implementación de un proyecto de riego y drenaje y que responda a los conceptos de desarrollo sustentable; haciendo énfasis en las perspectivas que deben considerarse para evaluar su impacto ambiental y en lo importante que resulta la participación de la población que será beneficiada en la confección y ejecución del proyecto."
Prevention of Programmed Cell Death of Sympathetic Neurons by the bcl-2 Proto-Oncogene (1992)

Approximately half of the neurons produced during embryogenesis normally die before adulthood. Although target-derived neurotrophic factors are known to be major determinants of programmed cell death--apoptosis--the molecular mechanisms by which trophic factors interfere with cell death regulation are largely unknown. Overexpression of the bcl-2 proto-oncogene in cultured sympathetic neurons has now been shown to prevent apoptosis normally induced by deprivation of nerve growth factor. This finding, together with the previous demonstration of bcl-2 expression in the nervous system, suggests that the Bcl-2 protein may be a major mediator of the effects of neurotrophic factors on neuronal survival.
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation (2010)

Previous studies have shown that the translation level of in vitro transcribed messenger RNA (mRNA) is enhanced when its uridines are replaced with pseudouridines; however, the reason for this enhancement has not been identified. Here, we demonstrate that in vitro transcripts containing uridine activate RNA-dependent protein kinase (PKR), which then phosphorylates translation initiation factor 2-alpha (eIF-2α), and inhibits translation. In contrast, in vitro transcribed mRNAs containing pseudouridine activate PKR to a lesser degree, and translation of pseudouridine-containing mRNAs is not repressed. RNA pull-down assays demonstrate that mRNA containing uridine is bound by PKR more efficiently than mRNA with pseudouridine. Finally, the role of PKR is validated by showing that pseudouridine- and uridine-containing RNAs were translated equally in PKR knockout cells. These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR.
The molecular chaperone TF55 (1994)

TF55‐like factor from Sulfolobus solfataricus was purified to homogeneity and analyzed by electron microscopy and image analysis to determine the symmetries of these particles. Three different procedures were used to analyze the electron micrographs: (1) fuzzy‐set based classification of the particles according to their rotational power spectra; (2) multivariate statistical analysis based on singular value decomposition; (3) circular harmonic analysis. Averages obtained from the three methods show unequivocally that the TF55‐like complex presents a 9‐fold symmetry.
A Current-Mode Comparator for Digital Calibration of Amorphous Silicon AMOLED Displays (2008)

We present a digital calibration driving scheme for stabilizing the uniformity of large area amorphous silicon active-matrix organic light emitting diode displays. A current-mode analog-to-digital converter (ADC) is used to extract the differential aging of the individual pixels. For the ADC, a configurable current comparator is designed that employs the output buffer of the source driver to reduce the die area. The comparator and pixel circuit were fabricated in 0.8-mum high-voltage CMOS and amorphous silicon technologies, respectively. Analysis and measurement results show a calibration refresh time of 2 s for a high-definition display (1920 times RGB times 1080). Moreover, the pixel current is highly stable despite a 5-V shift in the threshold voltage of the thin-film transistor driver.
Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction. (1987)

We measured bronchoalveolar lavage (BAL) fluid histamine levels in allergic asthmatics and nonallergic normal subjects after local airway antigen and cold 22 degrees C normal saline challenges. Immediately after instillation of antigen through a bronchoscope wedged into a subsegmental airway, all 17 allergic asthmatics but none of the nine normal subjects had visible airway constriction. The asthmatics had a concomitant mean increase in BAL histamine of 23% (P = 0.005), whereas the normals had no change in BAL histamine. Among the allergic asthmatics, the change in BAL histamine content in response to antigen directly correlated with the control (baseline) BAL histamine content (r = 0.66, P = 0.003). Moreover, asthmatics with large antigen-induced changes in BAL histamine had greater airway methacholine sensitivity than did asthmatics without measurable increases in BAL histamine (8 +/- 2 vs. 41 +/- 31 breath units). Neither asthmatics nor normal subjects had airway constriction or changes in BAL histamine levels in response to nonspecific challenge with cold saline. Our data suggest that when allergic asthmatics are exposed to relevant antigens they have in vivo lung mast cell degranulation which results in airway constriction and contributes to nonspecific airway hyperresponsiveness.
Cervical Cancer Cells with Positive Sox2 Expression Exhibit the Properties of Cancer Stem Cells (2014)

This study is the first to establish a functional link between endogenous Sox2 expression and CSCs in cervical carcinomas. Additionally, this study demonstrated that it is feasible to develop a tool to isolate CSCs from somatic tumors based on the expression of the endogenous nuclear protein Sox2 instead of cell surface markers.
Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. (1996)

Human adenoviruses have been developed as an attractive vehicle for in vivo liver-directed gene therapy. Problems with the application of first generation recombinant adenoviruses to liver-directed gene therapy have been transient expression of the recombinant gene and development of hepatitis. Previous studies in mouse models of gene transfer to liver and lung suggested that MHC class I-restricted cytotoxic T lymphocytes (CTLs) to viral antigens may be effectors in the elimination of transgene expression. The goal of this study was to evaluate the importance of viral antigens versus transgene product in inducing CTL mediated hepatocyte destruction in vivo. Immunization of C57BL/6 mice with a lacZ-expressing adenovirus elicited CTL responses to both viral antigens and the transgene product, beta-galactosidase (beta-gal). Adoptive transfer experiments, as well as studies involving lacZ-transgenic mice (ROSA-26) revealed that CTLs to viral antigens are sufficient to destroy virus-infected hepatocytes, indicating that CTLs to beta-gal can not solely account for the observed hepatocyte destruction that has characterized the use of first generation viruses. In addition, we confirmed that B cell-mediated events do not participate in destruction of hepatocytes in vivo, despite the production of virus- and beta-gal-specific antibodies. These data confirm the hypothesis that viral gene expression elicits host responses that contribute to the problem of transgene instability. Recombinant adenoviruses must be redesigned to diminish viral gene expression if they are to be used in the treatment of chronic diseases.
Neovascular Expression of E-Selectin, Intercellular Adhesion Molecule-1, and Vascular Cell Adhesion Molecule-1 in Human Atherosclerosis and Their Relation to Intimal Leukocyte Content (1996)

In atherosclerotic plaques, the expression of all three leukocyte adhesion molecules was more prevalent on intimal neovasculature than on arterial luminal endothelium. Further, the presence on neovasculature and nonendothelial cells of VCAM-1 and ICAM-1 was strongly associated with increased intimal leukocyte accumulation. These findings suggest that leukocyte recruitment through and/or activation of intimal neovasculature may play important roles in the pathogenesis of human atherosclerosis.
Dual Recognition of Double-Stranded DNA by 2′-Aminoethoxy-Modified Oligonucleotides (1998)

Simultaneous interaction of the 2'-aminoethoxy-modified oligonucleotides with the phosphodiester backbone (shown on the right, A) and with the bases through Hoogsteen base contacts (B) is seen at each base-pair step of the duplex DNA target. The electrostatic interaction between the protonated amino group and the negatively charged phosphate group provides for a dramatic increase in the binding affinity and the association rate constant.
Inhibition of tumor growth, vascularization, and collagenolysis in the rabbit cornea by medroxyprogesterone. (1981)

Medroxyprogesterone, dexamethasone, or cortisone, locally applied in sustained release polymer to rabbit V2 carcinoma implanted in the rabbit cornea, blocked neovascularization and three-dimensional growth of the tumor. These hormones similarly prevented the vascular proliferative response to implants in the rabbit cornea of mouse B-16 melanoma and also the response to implants of polymer containing tumor extract with angiogenesis activity. The inhibitory responses were accompanied by considerable reduction in collagenolytic activity released into culture medium by explants of the two tumors and of the corneal region containing angiogenic hepatoma extract. Morphologic studies revealed extensive three-dimensional disruption of the compact laminated collagenous structure of the cornea by untreated V2 carcinoma. In the presence of hormone the tumor grew slowly as a noninvasive two-dimensional plaque limited to the narrow region of the insertion pocket in the cornea, with no obvious disturbance of structure elsewhere. Cortisone was much les effective than medroxyprogesterone or dexamethasone. Testosterone and estradiol had no effect on the three measured properties. The data suggest that local hormonal interference with neovascularization, collagenase production, and tumor growth can prevent neoplastic invasion and destruction of a dense collagenous connective tissue.
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1 (2011)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
Pharyngeal Size and Resistance in Obstructive Sleep Apnea (1987)

Although anatomic and physiologic abnormalities of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea (OSA), the relative contributions of these factors have not been elucidated. We therefore measured pharyngeal cross-sectional area (PCSA) and pharyngeal air-flow resistance (Rp) in 12 overweight men with severe symptomatic OSA (mean apnea plus hypopnea index [AHI], 66.9 +/- 6.0 events per hour) and in 17 age- and weight-matched control subjects without spontaneous complaints of OSA symptoms (mean AHI, 4.9 +/- 1.6 events per hour). During wakefulness, PCSA was assessed during breath cessation at FRC by computed tomography (CT) and Rp by measuring inspiratory air-flow resistance between the choanae and epiglottis. No measure of PCSA differed significantly between patients and control subjects, and only 1 measure of PCSA, minimal pharyngeal area, correlated with AHI in all subjects (r = -0.38, p less than 0.05). In contrast, Rp was significantly higher (p less than 0.05) in patients (6.9 +/- 1.0 cm H2O/L/s) than in all control subjects (4.2 +/- 0.5 cm H2O/L/s) and correlated significantly with AHI (r = 0.53, p less than 0.01). We conclude that increased inspiratory resistance to air flow in the naso-oropharynx is present during wakefulness in overweight men with OSA, when compared with matched control subjects without symptomatic OSA, and is associated with disordered breathing during sleep. This occurs even though computed tomography is unable to demonstrate that pharyngeal size during wakefulness at FRC is significantly different between patients and control subjects. These observations suggest that the ability to dilate the pharynx during inspiration may be defective in patients with OSA.
Evidence for Homologous Actions of Pro-Opiocortin Products (1980)

alpha-Melanocyte-stimulating hormone (alpha-MSH), a modified fragment of adrenocorticotropic hormone, derives from the same biosynthetic route as beta-endorphin and is stored by the same arcuate neurons. Microinjection of alpha-melanocyte-stimulating hormone and several related peptides into the periaqueductal gray matter significantly reduced responsiveness to pain and had a behavioral profile similar to that produced by beta-endorphin.
Peptide synthesis using unprotected peptides through orthogonal coupling methods. (1995)

We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency.
Computerized scientific exhibit in radiology: a valuable format for delivering scientific information. (1994)

The computerized scientific exhibit (CSE) is gaining acceptance as a tool for delivering scientific information at meetings of radiologic societies. CSEs allow presentation of more material in a more space-efficient manner than do conventional exhibits, and the viewer can control the order and detail in which material is reviewed. As a disadvantage, currently, the radiologist must use a support team and learn new tools to create a CSE. The preparation and cost may also be greater. Meeting attendees must overcome a reluctance to use computers to benefit from a CSE. Creation of a CSE has design, production, and presentation phases. A team of content authors, software author, graphics acquisition person, and project manager works together through brainstorming, conceptual ordering, storyboarding, prototyping, and selection of authoring tools to design the exhibit. Production must include use of common word processing and image file formats, as well as standardization of image resolution. Accurate equipment specification is needed to ensure that the exhibit can be run on the equipment provided by the meeting organizers. In addition, some security steps are needed to prevent misuse of the exhibit. In addition to display at assemblies, the CSE can be made available to a larger audience by delivery on media such as compact disks and the Internet and can be continually modified as new material becomes available.
Nucleotides flanking a conserved TAAT core dictate the DNA binding specificity of three murine homeodomain proteins. (1993)

Murine homeobox genes play a fundamental role in directing embryogenesis by controlling gene expression during development. The homeobox encodes a DNA binding domain (the homeodomain) which presumably mediates interactions of homeodomain proteins with specific DNA sites in the control regions of target genes. However, the bases for these selective DNA-protein interactions are not well defined. In this report, we have characterized the DNA binding specificities of three murine homeodomain proteins, Hox 7.1, Hox 1.5, and En-1. We have identified optimal DNA binding sites for each of these proteins by using a random oligonucleotide selection strategy. Comparison of the sequences of the selected binding sites predicted a common consensus site that contained the motif (C/G)TAATTG. The TAAT core was essential for DNA binding activity, and the nucleotides flanking this core directed binding specificity. Whereas variations in the nucleotides flanking the 5' side of the TAAT core produced modest alterations in binding activity for all three proteins, perturbations of the nucleotides directly 3' of the core distinguished the binding specificity of Hox 1.5 from those of Hox 7.1 and En-1. These differences in binding activity reflected differences in the dissociation rates rather than the equilibrium constants of the protein-DNA complexes. Differences in DNA binding specificities observed in vitro may contribute to selective interactions of homeodomain proteins with potential binding sites in the control regions of target genes.