gebhart/patrepeval huggingface dataset:
Identification of canine helper T‐cell epitopes from the fusion protein of canine distemper virus (2001)

The fusion protein of canine distemper virus (CDV-F), a 662 amino-acid envelope protein, was used as the target molecule for identification of canine T helper (Th) epitopes. A library of 94 peptides, each 17 residues in length overlapping by 10 residues and covering the entire sequence of CDV-F, was screened using a lymphocyte proliferation assay with peripheral blood mononuclear cells (PBMC) obtained from dogs inoculated with canine distemper virus (CDV) vaccine. Initially we observed low and inconsistent proliferation of PBMC in response to these peptides, even when using cells obtained from dogs that had received multiple doses of CDV. Subsequently, the use of expanded cell populations derived by in vitro stimulation of canine PBMC with pools of peptides allowed the identification of a number of putative canine Th-epitopes within the protein sequence of CDV-F. There were two major clusters of Th-epitopes identified close to the cleavage site of the F0 fusion protein, while some others were scattered in both the F1 and F2 fragments of the protein. Some of these peptides, in particular peptide 35 (p35), were stimulatory in dogs of different breeds and ages. The identification of such promiscuous canine Th-epitopes encouraged us to assemble p35 in tandem with luteinising hormone releasing hormone (LHRH) a 10 amino-acid residue synthetic peptide representing a B-cell epitope which alone induces no antibody in dogs. The totally synthetic immunogen was able to induce the production of very high titres of antibodies against LHRH in all dogs tested. These results indicate that p35 could be an ideal candidate for use as a Th-epitope for use in outbred dogs.
El símbolo de la muerte (2004)

SB CSNB is characterized by retinal vascular impairment, as detected on OCTA.
A system for real time fluorescence imaging in color for tumor diagnosis (1987)

Early tumors can be diagnosed by the fluorescence of an injected, tumor-specific agent such as dihematoporphyrin ether. However, brightness or intensity contrast is low because of the autofluorescence of tissue. Addition of color (hue) information aids in detection of tumors, and in elimination of false positives. Standard color video cameras are not sensitive enough to image the weak fluorescence. Thus an intensified monochrome video camera has been equipped with a synchronized color filter wheel, and the image displayed by multiplexing alternate lines to a red green blue (RGB) monitor.
A Processed Pseudogene Codes for a New Antigen Recognized by a Cd8+ T Cell Clone on Melanoma (2000)

The M88.7 T cell clone recognizes an antigen presented by HLA B*1302 on the melanoma cell line M88. A cDNA encoding this antigen (NA88-A) was isolated using a library transfection approach. Analysis of the genomic gene's sequence identified it is a processed pseudogene, derived from a retrotranscript of mRNA coding for homeoprotein HPX42B. The NA88-A gene exhibits several premature stop codons, deletions, and insertions relative to the HPX42B gene. In NA88-A RNA, a short open reading frame codes for the peptide MTQGQHFLQKV from which antigenic peptides are derived; a stop codon follows the peptide's COOH-terminal Val codon. Part of the HPX42B mRNA's 3' untranslated region codes for a peptide of similar sequence (MTQGQHFSQKV). If produced, this peptide can be recognized by M88.7 T cells. However, in HPX42B mRNA, the peptide's COOH-terminal Val codon is followed by a Trp codon. As a result, expression of HPX42B mRNA does not lead to antigen production. A model is proposed for events that participated in creation of a gene coding for a melanoma antigen from a pseudogene.
Overlap integral factor enhancement using buried electrode structure in polymer Mach-Zehnder modulator (2008)

A buried coplanar waveguide (CPW) electrode for a polymer modulator is introduced in this letter. In this configuration, the electric and the optical fields are aligned and the overlap factor is enhanced. Thus, the poling efficiency can increase and Vπ decreases. Using two electro-optic polymers, Mach-Zehnder (MZ) modulators based on the buried electrode are demonstrated and compared to the in-plane CPW based MZ modulators. The measured Vπ’s of the buried CPW MZ’s are 6.7 and 4.3V for CLD1 and AJL8 devices, respectively, which give the overlap×r33 products of 19 and 30pm∕V. This shows 20% improvement in the overlap×poling efficiency by using the buried electrode.
The Prepared Mind (2006)

Insight occurs when problem solutions arise suddenly and seem obviously correct, and is associated with an "Aha!" experience. Prior theorizing concerning preparation that facilitates insight focused on solvers' problem-specific knowledge. We hypothesized that a distinct type of mental preparation, manifested in a distinct brain state, would facilitate insight problem solving independently of problem-specific knowledge. Consistent with this hypothesis, neural activity during a preparatory interval before subjects saw verbal problems predicted which problems they would subsequently solve with, versus without, self-reported insight. Specifically, electroencephalographic topography and frequency (Experiment 1) and functional magnetic resonance imaging signal (Experiment 2) both suggest that mental preparation leading to insight involves heightened activity in medial frontal areas associated with cognitive control and in temporal areas associated with semantic processing. The results for electroencephalographic topography suggest that noninsight preparation, in contrast, involves increased occipital activity consistent with an increase in externally directed visual attention. Thus, general preparatory mechanisms modulate problem-solving strategy.
Combined inhibition of VEGF‐ and PDGF‐signaling enforces tumor vessel regression by interfering with pericyte‐mediated endothelial cell survival mechanisms (2003)

Destruction of existing tumor blood vessels may be achieved by targeting vascular endothelial growth factor (VEGF) signaling, which mediates not only endothelial cell proliferation but also endothelial cell survival. In this study, however, intravital microscopy failed to demonstrate that targeting of VEGFR-2 (by the tyrosine kinase inhibitor SU5416) induces significant regression of experimental tumor blood vessels. Immunohistochemistry, electron microscopy, expression analyses, and in situ hybridization provide evidence that this resistance of tumor blood vessels to VEGFR-2 targeting is conferred by pericytes that stabilize blood vessels and provide endothelial cell survival signals via the Ang-1/Tie2 pathway. In contrast, targeting VEGFR-2 plus the platelet-derived growth factor receptor (PDGFR)-beta system (PDGFR-beta) signaling (by SU6668) rapidly forced 40% of tumor blood vessels into regression, rendering these tumors hypoxic as shown by phosphorescence quenching. TUNEL staining, electron microscopy, and apoptosis blocking experiments suggest that VEGFR-2 plus PDGFR-beta targeting enforced tumor blood vessel regression by inducing endothelial cell apoptosis. We further show that this is achieved by an interference with pericyte-endothelial cell interaction. This study provides novel insights into the mechanisms of how 1) pericytes may provide escape strategies to anti-angiogenic therapies and 2) novel concepts that target not only endothelial cells but also pericyte-associated pathways involved in vascular stabilization and maturation exert potent anti-vascular effects.
Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins (1996)

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI-1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell-bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.
In vitro studies on the selective binding of IgG from different species to tissue sections of the bovine mammary gland (1975)

Tissue sections of the mammary gland of cattle provide a sensitive and reproducible model for studying the initial events of the selective transport of bovine IgGs by the acinar epithelium (AE). Mammary tissue was reacted with purified antibody to horseradish peroxidase (HRP) and exposed to HRP. The sites of peroxidase activity were revealed cytochemically. The highly selective binding of IgGs by AE of the colostrum-forming gland but never of the lactating gland was most notable, whereas IgG1 and IgG2 subclasses and IgM and IgA lacked any binding capacity. An inhibition assay showed that the inhibitory capacity of IgGs was abolished by either alanylation or acetylation, whereas binding of IgGs was blocked by both Fab/c and isolated H-chains, but not by F(ab')2, Fab and Fc. The inhibitory pattern suggests that the region on the IgGs molecule involved in binding to the AE receptor may be located within the CH2 domain. In addition, IgG preparations of human, sheep and rabbit origin were found to be equally efficient in inhibiting the binding of IgGs to AE, whereas no inhibition was obtained with nonmammalian (turtle and chicken) IgG. Similarly, human myeloma proteins of the subclasses IgG1 and IgG3 caused complete inhibition, while IgG2 and IgG4 were inefficient. It is suggested that molecular evolution of IgG within mammalian species is accompanied by the conservation of structures fitting to receptors on the cell surface of different species.
Activation of the mammalian target of rapamycin signalling pathway in epidermal tumours and its correlation with cyclin-dependent kinase 2 (2009)

Constitutive activation of the AKT/mTOR pathway was frequent in epidermal tumours, especially in malignant tumours. Activation was highly correlated with CDK2 expression, suggesting that the AKT/mTOR pathway may induce the malignant transition through CDK2 in epidermal tumours.
Optimization of steam explosion as a method for increasing susceptibility of sugarcane bagasse to enzymatic saccharification (1987)

The technique of autohydrolysis steam explosion was examined as a means for pretreatment of sugarcane bagasse. Treatment conditions were optimized so that following enzymatic hydrolysis, pretreated bagasse would give 65.1 g sugars/100 g starting bagasse. Released sugars comprised 38.9 g glucose, 0.6 g cellobiose, 22.1 g xylose, and 3.5 g arabinose, and were equivalent to 83% of the anhydroglucan and 84% of the anhydroxylan content of untreated bagasse. Optimum conditions were treatment for 30 S with saturated steam at 220 degrees C with a water-to-solids ratio of 2 and the addition of 1 g H(2)SO(4)/100 g dry bagasse. Bagasse treated in this manner was not inhibitory to fermentation by Saccharomyces uvarum except at low inoculum levels when fermentation time was extended by up to 24 h. Pretreated saccharified bagasse was inhibitory to Pachysolen tannophilus and this was attributed to the formation of acetate from the hydrolysis of acetyl groups present in hemicellulose. The major advantage of the pretreatment is the achievement of high total sugar yield with moderate enzyme requirement and only minor losses due to sugar decomposition.
New Series of Morpholine and 1,4-Oxazepane Derivatives as Dopamine D4Receptor Ligands:  Synthesis and 3D-QSAR Model (2004)

Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthesis of a new series of 2,4-disubstituted morpholines and 2,4-disubstituted 1,4-oxazepanes with selectivity for the dopamine D(4) receptor. A 3D-QSAR analysis using the GRID/GOLPE methodology was performed with the purpose to get a better understanding of the relationship between chemical structure and biological activity. Inspection of the coefficient plots allowed us to identify that regions which are important for affinity are situated around the two benzene ring systems, a p-chlorobenzyl group, and the aliphatic amine belonging to the morpholine or 1,4-oxazepane system. In addition, the size of the morpholine or 1,4-oxazepane ring seems to be important for affinity.
Novel treatment options for ulcerative colitis (2013)

The approved treatment options for patients with ulcerative colitis (UC) are currently limited to mesalamine or immunosuppressants. Patients who do not respond to mesalamine-based therapy can be treated with immunomodulators or anti-TNF antibody therapy. Failure or adverse reactions to these medications leaves the patient with little choice other than colectomy. However, novel insights into the pathogenic drivers of UC have led to new developments in drugs that promise clinical efficacy via modulation of targeted pathways. Given the impending expansion of therapeutic options for patients with UC, clinicians and researchers should be familiar with these mechanisms of action. In addition, the typical 'step-up' treatment paradigm for UC will likely need to be reshaped to allow for a more personalized approach to treating UC.
Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism (2001)

The importance of the nuclear receptor nurr1 for the appropriate development of mesencephalic dopamine-synthesizing neurons has been clearly demonstrated through the targeted disruption of the nurr1 gene. The persistence of nurr1 expression in adult tissue suggests a possible role for this transcription factor in the maintenance, as well as development, of the dopaminergic phenotype. To address this issue, we analyzed the effects of nurr1 on the transcriptional expression of the human dopamine transporter gene (hDAT), one of the most specific phenotypic markers for dopaminergic neurons. Nurr1 enhanced the transcriptional activity of hDAT gene constructs transiently transfected into a newly described cell line (SN4741) that expresses a dopaminergic phenotype, whereas other members of the NGFI-B subfamily of nuclear receptors had lesser or no effects. Nurr1 activation of hDAT was not dependent upon heterodimerization with the retinoid X receptor. Unexpectedly, functional analysis of a series of gene constructs revealed that a region of the hDAT 5'-flanking sequence devoid of NGFI-B response element (NBRE)-like sites mediated nurr1 activation. Additional experiments using a nurr1 mutant construct suggest that nurr1 activates hDAT transcription via a novel NBRE-independent mechanism.
Construction of mRNA genes for the synthesis and translation of duck alpha globin mRNA. (1989)

In studies of the effects of changes in mRNA structure and sequence on the initiation of protein synthesis, we used a generally applicable approach to transcribe reconstructed genes for duck alpha A globin by the bacteriophage SP6 RNA polymerase promoter in a pGEM-2 plasmid vector. The genes were reconstructed such that the first nucleotide to be transcribed, the 5' adenosine, was placed directly adjacent to the SP6 promoter sequence. The 3' ends of the genes were constructed such that cleavage with Ssp 1 endonuclease yielded a template that directed the synthesis of mRNA terminating in a poly A tail containing 56 adenosines and a single 3' uridine. Special conditions using a Mn++ buffer were developed to enable the SP6 RNA polymerase to initiate at the 5' adenosine and synthesize the A-start transcription product. The mRNA could be capped and was subsequently used as an effective template for in vitro translation and synthesis of duck alpha A globin.
Discovery of AZD3839, a Potent and Selective BACE1 Inhibitor Clinical Candidate for the Treatment of Alzheimer Disease (2012)

β-Site amyloid precursor protein cleaving enzyme1 (BACE1) is one of the key enzymes involved in the processing of the amyloid precursor protein (APP) and formation of amyloid β peptide (Aβ) species. Because cerebral deposition of Aβ species might be critical for the pathogenesis of Alzheimer disease, BACE1 has emerged as a key target for the treatment of this disease. Here, we report the discovery and comprehensive preclinical characterization of AZD3839, a potent and selective inhibitor of human BACE1. AZD3839 was identified using fragment-based screening and structure-based design. In a concentration-dependent manner, AZD3839 inhibited BACE1 activity in a biochemical fluorescence resonance energy transfer (FRET) assay, Aβ and sAPPβ release from modified and wild-type human SH-SY5Y cells and mouse N2A cells as well as from mouse and guinea pig primary cortical neurons. Selectivity against BACE2 and cathepsin D was 14 and >1000-fold, respectively. AZD3839 exhibited dose- and time-dependent lowering of plasma, brain, and cerebrospinal fluid Aβ levels in mouse, guinea pig, and non-human primate. Pharmacokinetic/pharmacodynamic analyses of mouse and guinea pig data showed a good correlation between the potency of AZD3839 in primary cortical neurons and in vivo brain effects. These results suggest that AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species. It might, therefore, have disease-modifying potential in the treatment of Alzheimer disease and related dementias. Based on the overall pharmacological profile and its drug like properties, AZD3839 has been progressed into Phase 1 clinical trials in man.
An n-Channel Two-Dimensional Covalent Organic Framework (2011)

Co-condensation of metallophthalocyanine with an electron-deficient benzothiadiazole (BTDA) block leads to the formation of a two-dimensional covalent organic framework (2D-NiPc-BTDA COF) that assumes a belt shape and consists of AA stacking of 2D polymer sheets. Integration of BTDA blocks at the edges of a tetragonal metallophthalocyanine COF causes drastic changes in the carrier-transport mode and a switch from a hole-transporting skeleton to an electron-transporting framework. 2D-NiPc-BTDA COF exhibits broad and enhanced absorbance up to 1000 nm, shows panchromatic photoconductivity, is highly sensitive to near-infrared photons, and has excellent electron mobility as high as 0.6 cm(2) V(-1) s(-1).
Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6. (2000)

Kaposi's sarcoma-associated herpes virus (KSHV) is associated with Kaposi's sarcoma, multicentric Castleman's disease, and body cavity-based lymphomas, settings in which human interleukin-6 (hIL-6) acts as a growth factor. The KSHV open reading frame K2 encodes for viral IL-6 (vIL-6), a protein with 25% amino acid identity to hIL-6, which can promote the growth of hIL-6-dependent cell lines. In the present study, we characterized biological sequelae and signaling cascades triggered by hIL-6 versus vIL-6 in the hIL-6-dependent MH60 and B9 cell lines. Both hIL-6 and vIL-6 induced significant increases (P < 0.01) in DNA synthesis in these cell lines in a dose-dependent fashion. Neutralizing anti-hIL-6 antibody (Ab) inhibited DNA synthesis triggered by hIL-6, without similarly affecting proliferation in response to vIL-6. On the other hand, antimouse IL-6 receptor (mIL-6R) Ab blocked response to vIL-6, but not that to hIL-6. Both hIL-6 and vIL-6 activated gp130, Janus kinase 1, signal transducers and activators of transcription-3, and mitogen-activated protein kinase in both MH60 and B9 cells. Proliferation of these cell lines in response to both hIL-6 and vIL-6 was blocked by PD98059, an inhibitor of MEK1 activation. These data suggest that MEK1 activation mediates the proliferative response to both cytokines. Finally, both hIL-6 and vIL-6 also maintained viability of serum-starved MH60 and B9 cells and blocked dexamethasone-induced apoptosis of MM.1S human myeloma cells. Further characterization of the signaling cascades mediating the growth and antiapoptotic effects of vIL-6 versus hIL-6 may help identify their unique roles in disease pathogenesis in Kaposi's sarcoma and other KSHV-associated neoplasms.
A WT1 antisense oligonucleotide inhibits proliferation and induces apoptosis in myeloid leukaemia cell lines. (1996)

The response of the CML-BC cell line, K562, the myelomonocytic cell line MM6 and the promyelocytic leukaemia cell line HL-60, to a 15 mer WT1 antisense oligonucleotide, targeted to the translation initiation site of the WT1 mRNA was examined. K562 cells exposed to 0.4 microM antisense oligonucleotide showed markedly reduced proliferation which was associated with reduced cell viability. Sense, scrambled and mutant antisense oligonucleotides had no effect on the proliferation of K562 cells. MM6 cells exposed to 0.4 microM antisense oligonucleotide also showed significantly reduced cellular proliferation which was also accompanied by loss of cell viability. In the K562 and MM6 antisense cultures that exhibited reduced cell viability, both DNA fragmentation and morphological features consistent with apoptosis could be identified. In contrast the growth of HL-60 cells was unaffected by exposure to 0.4 microM antisense oligonucleotide. In each of the cell lines examined, WT1 antisense oligonucleotide abrogated WT1 protein expression, and analysis of WT1 coding sequence in these cells showed that no oncogenic point mutations in the gene were present. We propose therefore that in some myeloid leukaemia cell lines, the expression of a normal WT1 protein is necessary for cell proliferation and that it plays a role in maintaining the viability of some leukaemia cells.
Herbimycin, a new antibiotic produced by a strain of Streptomyces. (1979)

Herbimycin, a new antibiotic, was isolated from the fermentation broth of Streptomyces hygroscopicus strain No. AM-3672, a soil isolate. The molecular formula of herbimycin was determined to be C30H42N2O9. Herbimycin was found to have potent herbicidal activity against most mono- and di-cotyledonous plants, especially against Cyperus microiria STEUD. However, Oryza sativa showed strong resistance to herbimycin.