gebhart/patrepeval huggingface dataset:
Effects of translation initiation factor eIF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunodeficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding (1995)

The viral transactivator proteins Rex and Rev are necessary for the expression of structural proteins of human T-cell leukemia virus type I and human immunodeficiency virus type 1, respectively. Although the interaction of Rex/Rev with a cellular cofactor(s) has been thought to be required for Rex/Rev action, there is no suitable system to search for the cofactor(s) in mammalian cells. We found that a Rex mutant, TAgRex, which contains a simian virus 40 nuclear localization signal in place of the N-terminal 19 amino acids of Rex, could dominantly inhibit wild-type Rex/Rev functions. The inhibition did not require either Rev response element/Rex response element binding or the oligomerization ability of the mutant, but it did require a region around amino acid 90 of the Rex protein, suggesting that TAgRex sequestered the cellular cofactor. Complementation with the eukaryotic translation initiation factor 5A (eIF-5A) in this system could restore the impaired Rex function. These results indicate that eIF-5A is the cofactor indispensable for Rex function. Additionally, by using a two-hybrid system, the homo-oligomer formation of Rex was found to be mediated by the region around amino acid 90 in addition to Tyr-64 and Trp-65 of Rex protein. Thus, eIF-5A may play a part in the formation of the Rex homo-oligomer.
RIP and FADD: two "death domain"-containing proteins can induce apoptosis by convergent, but dissociable, pathways. (1996)

With use of the yeast two-hybrid system, the proteins RIP and FADD/MORT1 have been shown to interact with the "death domain" of the Fas receptor. Both of these proteins induce apoptosis in mammalian cells. Using receptor fusion constructs, we provide evidence that the self-association of the death domain of RIP by itself is sufficient to elicit apoptosis. However, both the death domain and the adjacent alpha-helical region of RIP are required for the optimal cell killing induced by the overexpression of this gene. By contrast, FADD's ability to induce cell death does not depend on crosslinking. Furthermore, RIP and FADD appear to activate different apoptotic pathways since RIP is able to induce cell death in a cell line that is resistant to the apoptotic effects of Fas, tumor necrosis factor, and FADD. Consistent with this, a dominant negative mutant of FADD, lacking its N-terminal domain, blocks apoptosis induced by RIP but not by FADD. Since both pathways are blocked by CrmA, the interleukin 1 beta converting enzyme family protease inhibitor, these results suggest that FADD and RIP can act along separable pathways that nonetheless converge on a member of the interleukin 1 beta converting enzyme family of cysteine proteases.
Different neurotrophins are expressed and act in a developmental sequence to promote the survival of embryonic sensory neurons (1993)

To investigate if different neurotrophins regulate the survival of neurons at successive developmental stages, we studied the effect of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the survival of mouse trigeminal neurons at closely staged intervals in development. We show that during the earliest stages of target field innervation trigeminal neurons display a transitory survival response to BDNF and NT-3. This response is lost as the neurons become NGF-dependent shortly before neuronal death begins in the trigeminal ganglion. BDNF and NT-3 mRNAs are expressed in the peripheral trigeminal target field before the arrival of the earliest axons and the onset of NGF mRNA expression. The levels of BDNF and NT-3 mRNAs peak during the early stages of target field innervation and decline shortly after the loss of neuronal responsiveness to BDNF and NT-3. Our study provides the first clear evidence that different target-derived neurotrophins can act sequentially to promote the survival of developing neurons.
Structure−Brain Exposure Relationships (2006)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTStructure−Brain Exposure RelationshipsStephen A. Hitchcock and Lewis D. PenningtonView Author Information Chemistry Research & Discovery, Amgen, One Amgen Center Drive, Thousand Oaks, California 91320-1799 Cite this: J. Med. Chem. 2006, 49, 26, 7559–7583Publication Date (Web):December 5, 2006Publication History Received30 May 2006Published online5 December 2006Published inissue 1 December 2006https://pubs.acs.org/doi/10.1021/jm060642ihttps://doi.org/10.1021/jm060642ireview-articleACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views8747Altmetric-Citations544LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Antibiotic resistance,Central nervous system,Permeability,Pharmaceuticals,Rodent models Get e-Alerts
A somatic cell hybrid map of the long arm of human chromosome 17, containing the familial breast cancer locus (BRCA1). (1993)

We describe a detailed somatic cell hybrid map of human chromosome 17q11.2-q23, containing the familial breast and ovarian cancer locus (BRCA1) and highly informative closely linked markers. An X-irradiation panel of 38 hamster/human and mouse/human hybrids with fragments of chromosome 17 was generated and characterized with 22 STS markers from this chromosome. A detailed map of 61 probes onto chromosome 17q, subdividing the chromosome arm into 25 regions, was done by using a panel of hybrids with well-defined breakpoints and nine chromosome-mediated gene transfectants. Our localization of RARA, TOP2, EDH17B1 and 2, and possibly WNT3, between THRA1 and D17S181, two markers known to flank BRCA1, suggests that any of these is a potential candidate for the BRCA1 locus. The marker D17S579 (Mfd188), which is believed to be very close to BRCA1, maps closest to the EDH17B genes.
Recognition of Higher Order Patterns in Proteins: Immunologic Kernels (2013)

By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC-I and MHC-II binding peptides. Such "immunologic kernel" peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.
BH3-based Fusion Artificial Peptide Induces Apoptosis and Targets Human Colon Cancer (2009)

Dysregulation of apoptosis is a pilot event before cancer development and plays important roles for cancer to develop resistance to chemical therapeutics. So exploring strategies to recovery the apoptosis balance is a charming and long-endeavored aim in the attempts to conquer cancers. The present study shows an exciting potency of a fusion peptide to inhibit and target to cancer cells, which is composed of BH3 (Bcl-2 Homology 3) effector domain from PUMA (p53 upregulated modulator of apoptosis) and targeting domain of trans-activator of transcription (TAT) and DV3. The in vitro results demonstrated cancer growth inhibition by the fusion peptide in colon cancer cells, as well as in lung adenocarcinoma cell line and breast carcinoma cell line of human origin. But the viability of HEK293, a noncancerous cell line, was not affected, indicating the cancer specificity of the fusion peptide. Apoptosis activation was induced by the peptide through the mitochondria pathway. In vivo studies displayed its tumor inhibiting ability by intratumoral injection. When the fusion peptide was administered systematically by tail vein, the peptide targeted the established tumors in nude mice. No other organs were significantly involved. The fusion peptide is an artificially designed molecule worthy of further evaluation and development.
Interruption of Homologous Desensitization in Cyclic Guanosine 3′,5′-Monophosphate Signaling Restores Colon Cancer Cytostasis by Bacterial Enterotoxins (2005)

Bacterial diarrheagenic heat-stable enterotoxins induce colon cancer cell cytostasis by targeting guanylyl cyclase C (GCC) signaling. Anticancer actions of these toxins are mediated by cyclic guanosine 3',5'-monophosphate (cGMP)-dependent influx of Ca2+ through cyclic nucleotide-gated channels. However, prolonged stimulation of GCC produces resistance in tumor cells to heat-stable enterotoxin-induced cytostasis. Resistance reflects rapid (tachyphylaxis) and slow (bradyphylaxis) mechanisms of desensitization induced by cGMP. Tachyphylaxis is mediated by cGMP-dependent protein kinase, which limits the conductance of cyclic nucleotide-gated channels, reducing the influx of Ca2+ propagating the antiproliferative signal from the membrane to the nucleus. In contrast, bradyphylaxis is mediated by cGMP-dependent allosteric activation of phosphodiesterase 5, which shapes the amplitude and duration of heat-stable enterotoxin-dependent cyclic nucleotide accumulation required for cytostasis. Importantly, interruption of tachyphylaxis and bradyphylaxis restores cancer cell cytostasis induced by heat-stable enterotoxins. Thus, regimens that incorporate cytostatic bacterial enterotoxins and inhibitors of cGMP-mediated desensitization offer a previously unrecognized therapeutic paradigm for treatment and prevention of colorectal cancer.
Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28− Regulatory T Lymphocytes by TCR Crosslinking (2009)

Zwitterionic capsular polysaccharides (ZPS) of commensal bacteria are characterized by having both positive and negative charged substituents on each repeating unit of a highly repetitive structure that has an alpha-helix configuration. In this paper we look at the immune response of CD8(+) T cells to ZPSs. Intraperitoneal application of the ZPS Sp1 from Streptococcus pneumoniae serotype 1 induces CD8(+)CD28(-) T cells in the spleen and peritoneal cavity of WT mice. However, chemically modified Sp1 (mSp1) without the positive charge and resembling common negatively charged polysaccharides fails to induce CD8(+)CD28(-) T lymphocytes. The Sp1-induced CD8(+)CD28(-) T lymphocytes are CD122(low)CTLA-4(+)CD39(+). They synthesize IL-10 and TGF-beta. The Sp1-induced CD8(+)CD28(-) T cells exhibit immunosuppressive properties on CD4(+) T cells in vivo and in vitro. Experimental approaches to elucidate the mechanism of CD8(+) T cell activation by Sp1 demonstrate in a dimeric MHC class I-Ig model that Sp1 induces CD8(+) T cell activation by enhancing crosslinking of TCR. The expansion of CD8(+)CD28(-) T cells is independent, of direct antigen-presenting cell/T cell contact and, to the specificity of the T cell receptor (TCR). In CD8(+)CD28(-) T cells, Sp1 enhances Zap-70 phosphorylation and increasingly involves NF-kappaB which ultimately results in protection versus apoptosis and cell death and promotes survival and accumulation of the CD8(+)CD28(-) population. This is the first description of a naturally occurring bacterial antigen that is able to induce suppressive CD8(+)CD28(-) T lymphocytes in vivo and in vitro. The underlying mechanism of CD8(+) T cell activation appears to rely on enhanced TCR crosslinking. The data provides evidence that ZPS of commensal bacteria play an important role in peripheral tolerance mechanisms and the maintenance of the homeostasis of the immune system.
Position‐specific expression of Hox genes along the gastrointestinal tract (2004)

Hox genes play a critical role in morphogenesis of the early embryo along the anteroposterior axis. In mammals, 39 Hox genes with extensive homology are organized into 13 paralogous groups, forming four clusters on four separate chromosomes. The genes within each cluster are arranged in a 3' to 5' direction and expressed in a temporally and spatially coordinated manner along the anteroposterior axis in the vertebrae, limbs and viscera, including the gastrointestinal tract, but little is known about their spatial expression in the adult gastrointestinal tract. We used the quantitative polymerase chain reaction (PCR) intercalater method with SYBR Green to quantify human Hox gene expression in the adult gastrointestinal tract tissue: esophagus, stomach, duodenum, jejunum, ileum, ileocecum, cecum, ascending colon, transverse colon, descending colon and rectum. Hox gene expression was normalized to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) gene expression. The spatial expression pattern was analyzed by the multivariate method. The expression level of all 39 Hox genes could be measured in a reproducible manner. Genes with higher expression in the foregut-derived segments tended to have lower expression in hindgut-derived segments, whereas those with low expression in the former tended to have higher in the latter. Principal components analysis and permax analysis revealed a position-specific expression pattern of Hox genes along the anteroposterior axis of the adult gastrointestinal tract. The pattern recapitulates the expression pattern in the embryonic gastrointestinal tract. We suggest that Hox genes may play a pivotal role in the position-specific regenerative process of intestinal epithelial cells.
Identification of a Pharmacophore for Thrombopoietic Activity of Small, Non-Peptidyl Molecules. 2. Rational Design of Naphtho[1,2-d]imidazole Thrombopoietin Mimics (2002)

The invention of a new class of naphtho[1,2-d]imidazole thrombopoietin mimics based on a pharmacophore hypothesis for small-molecule thrombopoietic agonists is discussed. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in TPO mimetic potencies and efficacies.
Pulmonary Angiography, Ventilation Lung Scanning, and Venography for Clinically Suspected Pulmonary Embolism with Abnormal Perfusion Lung Scan (1983)

Inherent contradictions in current diagnostic recommendations for pulmonary embolism have created considerable confusion and controversy. To resolve these contradictions, we did a prospective study of ventilation-perfusion scanning, pulmonary angiography, and venography in consecutive patients with clinically suspected pulmonary embolism and abnormal perfusion scans. Ventilation scanning increased the probability of pulmonary embolism in patients with large perfusion defects and ventilation mismatch, but a ventilation-perfusion match was not helpful in ruling out pulmonary embolism. Small perfusion defects with mismatch had neither sufficiently high nor low probability to be of diagnostic value. The observed frequency of proximal vein thrombosis (19% to 51%) and its association with the range of ventilation-perfusion defects have important implications for management of pulmonary embolism. Pulmonary angiography is required in combination with venography in most patients with perfusion abnormalities because the probability of pulmonary embolism is neither sufficiently high nor low to confirm or exclude pulmonary embolism.
Identifying Noun Product Features that Imply Opinions (2011)

Identifying domain-dependent opinion words is a key problem in opinion mining and has been studied by several researchers. However, existing work has been focused on adjectives and to some extent verbs. Limited work has been done on nouns and noun phrases. In our work, we used the feature-based opinion mining model, and we found that in some domains nouns and noun phrases that indicate product features may also imply opinions. In many such cases, these nouns are not subjective but objective. Their involved sentences are also objective sentences and imply positive or negative opinions. Identifying such nouns and noun phrases and their polarities is very challenging but critical for effective opinion mining in these domains. To the best of our knowledge, this problem has not been studied in the literature. This paper proposes a method to deal with the problem. Experimental results based on real-life datasets show promising results. 1
Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. (1993)

The v-maf oncogene of the avian musculoaponeurotic fibrosarcoma virus, AS42, encodes a nuclear protein which contains a characteristic b-Zip domain. By screening a chicken embryo fibroblast (CEF) cDNA library under moderately stringent hybridization conditions, we picked up a series of cDNA clones for a novel maf-related gene which we named mafK. We also identified another maf-related gene named mafF by screening a chicken genomic library using a mafK probe. Structural analyses suggested that the mafK and mafF genes consist of three exons. The exon-intron structures of the two genes resemble each other, but differ from that of the chicken c-maf gene. As compared to the c-Maf protein, the proteins encoded by the mafK and the mafF genes are rather small in size and lack the regions corresponding to the amino terminal acidic domain present in the c-Maf protein. On the other hand, the structures of the b-Zip domain are well conserved among these Maf-related proteins. When overexpressed by using an avian retroviral vector, the two maf-related genes did not induce morphological transformation of CEF cells but induced colony formation in soft agar with very low efficiencies. With a specific antibody, the MafK protein was detected predominantly in the nuclei of the cells infected with the virus which carries the mafK gene. Tissue distributions of these three maf-family genes are different from one another, probably reflecting their different functions in vivo.
A genomic approach to scoliosis pathogenesis (1999)

Genetic predisposition contributes to scoliosis in humans. Two syndromes of primary scoliosis occur--congenital scoliosis, which presents at birth, often associated with other abnormalities, and idiopathic scoliosis which becomes apparent between infancy and adolescence. Little is known regarding the genetic transmission of scoliosis risk. Data gleaned from mouse mutations provide a valuable supplement to human family studies. More than 50 mouse mutations include scoliosis, kyphosis, or tail kinks as a phenotype; the locations of the human homologues for 28 of these can be predicted on the basis of synteny conservation. Some mouse mutations are either more penetrant or more fully expressed in one sex. The mouse data provide a basis both for optimism and for caution in understanding human scoliosis. Mouse models provide insight into mechanisms underlying spinal curvature and help direct searches for genes important in human disease. Four types of defects account for most mouse scoliosis: defects of cell-cell communication, intracellular signal transduction, matrix protein synthesis, and matrix protein metabolism. Mouse data suggest that at least two types of heterogeneity complicate genetic analysis: locus heterogeneity, in which lesions of distinct genes lead to a similar phenotype, and allelic heterogeneity, in which the phenotypes arising from alleles of a single gene differ. By focusing initial studies on multiplex families with apparent simple Mendelian inheritance the effect of heterogeneity is minimized.
WiFO: Hybrid WiFi and Free-Space Optical Communication System with PAM Optimal Decoding (2016)

We describe WiFO, a novel communication system that integrates free space optical communication and WiFi technologies to provide an order of magnitude improvement in wireless capacity. To provide high bit rates and large coverage, WiFO employs an array of LED-based transmitters. Each modulates a beam of invisible light using a Pulse Amplitude Modulation (PAM) scheme. A WiFO receiver is capable of receiving signals from multiple transmitters simultaneously. We describe a PAM decoding scheme that estimates the channel parameters, then use them to determine the decoding thresholds for minimizing the bit error rate. Furthermore, we characterize the conditions on channel parameters for perfect signal recovery. Simulations and theoretical analyses are provided to validate the proposed scheme.
Photomodulation of Oxidative Metabolism and Electron Chain Enzymes in Rat Liver Mitochondria (1997)

Low-level laser irradiation has been applied in a variety of laboratory studies and clinical trials for photobiostimulation over the last three decades. Considerable skepticism exists regarding the concept of photostimulation within the medical community. One of the major difficulties with photoirradiation research is that it lacks experimentally supportable mechanisms for the alleged photobiostimulatory effects. This study was undertaken to determine whether oxidative metabolism and electron chain enzymes in rat liver mitochondria can be modulated by photoirradiation. Oxygen consumption, phosphate potential, and energy charge of rat liver mitochondria were determined following photoirradiation. Activities of mitochondrial enzymes were analyzed to assess the specific enzymes that are directly involved with the photostimulatory process. An argon-dye laser at a wave-length of 660 nm and at a power density of 10 mW/cm2 was used as a photon source. Photoirradiation significantly increased oxygen consumption (0.6 J/cm2 and 1.2 J/cm2, P < 0.05), phosphate potential, and the energy charge (1.8 J/cm2 and 2.4 J/cm2, P < 0.05) of rat liver mitochondria and enhanced the activities of NADH: ubiquinone oxidoreductase, ubiquinol: ferricytochrome C oxidoreductase and ferrocytochrome C: oxygen oxidoreductase (0.6 J/cm2, 1.2 J/cm2, 2.4 J/cm2 and 4.8 J/cm2, P < 0.05). The activities of succinate ubiquinone oxidoreductase, ATPase, and lactate dehydrogenase were not affected by photoirradiation.