gebhart/patrepeval huggingface dataset:
Comparative integromics on Eph family (2006)

EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHA10, EPHB1, EPHB2, EPHB3, EPHB4 and EPHB6 are EPH family receptors for Ephrin family ligands. Ephrin/EPH signaling pathway networks with the WNT signaling pathway during embryogenesis, tissue regeneration, and carcinogenesis. TCF/LEF-binding sites within the promoter region of human EPH family members were searched for by using bioinformatics and human intelligence. Because five TCF/LEF-binding sites were identified within the 5'-promoter region of the EPHA7 gene, comparative genomics analyses on EPHA7 orthologs were further performed. EPHA7-MANEA-FHL5 locus at human chromosome 6q16.1 and EPHA10-MANEAL-FHL3 locus at human chromosome 1p34.3 were paralogous regions within the human genome. Human EPHA7 mRNA was expressed in embryonic stem (ES) cells, neural tissues, duodenal cancer and parathyroid tumors, while mouse Epha7 mRNA was expressed in fertilized egg, Rathke's pouche, visual cortex, pituitary gland, other neural tissues, pancreas, lung tumors and mammary tumors. The chimpanzee EPHA7 gene and cow Epha7 gene were identified within NW_107969.1 and AC155055.2 genome sequences, respectively. Five TCF/LEF-binding sites within human EPHA7 promoter were conserved in the chimpanzee EPHA7 promoter, and three TCF/LEF-binding sites in the cow Epha7 promoter, but none in the mouse Epha7 promoter. Primates and cow EPHA7 orthologs were identified as evolutionarily conserved targets of the WNT/beta-catenin signaling pathway. D6S1056 microsatellite marker within EPHA7 gene is deleted in prostate cancer. Deletion and/or promoter CpG hypermethylation could explain the EPHA7 down-regulation in human tumors. EPHA7 is a target of systems medicine, especially in the fields of regenerative medicine and oncology.
Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease (2006)

In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
Localization of the Endocannabinoid-Degrading Enzyme Fatty Acid Amide Hydrolase in Rat Dorsal Root Ganglion Cells and Its Regulation after Peripheral Nerve Injury (2009)

Fatty acid amide hydrolase (FAAH) is a degradative enzyme for a group of endogenous signaling lipids that includes anandamide (AEA). AEA acts as an endocannabinoid and an endovanilloid by activating cannabinoid and vanilloid type 1 transient receptor potential (TRPV1) receptors, respectively, on dorsal root ganglion (DRG) sensory neurons. Inhibition of FAAH activity increases AEA concentrations in nervous tissue and reduces sensory hypersensitivity in animal pain models. Using immunohistochemistry, Western blotting, and reverse transcription-PCR, we demonstrate the location of the FAAH in adult rat DRG, sciatic nerve, and spinal cord. In naive rats, FAAH immunoreactivity localized to the soma of 32.7 +/- 0.8% of neurons in L4 and L5 DRG. These were small-sized (mean soma area, 395.96 +/- 5.6 mum(2)) and predominantly colabeled with peripherin and isolectin B4 markers of unmyelinated C-fiber neurons; 68% colabeled with antibodies to TRPV1 (marker of nociceptive DRG neurons), and <2% colabeled with NF200 (marker of large myelinated neurons). FAAH-IR was also present in small, NF200-negative cultured rat DRG neurons. Incubation of these cultures with the FAAH inhibitor URB597 increased AEA-evoked cobalt uptake in a capsazepine-sensitive manner. After sciatic nerve axotomy, there was a rightward shift in the cell-size distribution of FAAH-immunoreactive (IR) DRG neurons ipsilateral to injury: FAAH immunoreactivity was detected in larger-sized cells that colabeled with NF200. An ipsilateral versus contralateral increase in both the size and proportion of FAAH-IR DRG occurred after spinal nerve transection injury but not after chronic inflammation of the rat hindpaw 2 d after injection of complete Freund's adjuvant. This study reveals the location of FAAH in neural tissue involved in peripheral nociceptive transmission.
The synthesis and antiviral activity of some 4'-thio-2'-deoxy nucleoside analogs (1991)

Starting from benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro- pentofuranoside (4), the following 2'-deoxy nucleoside analogues have been synthesized: 4'-thiothymidine (8), 3'-azido-4'-thio- deoxythymidine (10), and (E)-5-(2-bromovinyl)-4'-thio-2'-deoxyuridine (22). The first compound is toxic, the second is not toxic nor has detectable biological activity, and the third is not toxic and has significant activity against some herpesviruses.
The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation. (1993)

The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or last hydrophobic amino acids in the highly conserved ninth heptad of chick T3R alpha [cT3R alpha(L365R) and cT3R(L372R)] and human RAR alpha (hRAR alpha) [hRAR(M377R) and hRAR(L384R)] reveal that this heptad is essential for certain heterodimeric interactions and for diverse functional activities. Without ligands, wild-type receptors form both homodimers and heterodimers, while these mutants form only homodimers. Surprisingly, the cognate ligand for each mutant enables heterodimer formation between cT3R(L365R) and RAR or RXR and between hRAR(M377R) and T3R or RXR. Both cT3R(L365R) and hRAR(M377R) mediate ligand-dependent transcriptional regulation. However, unlike the wild-type receptor, non-ligand-associated cT3R(L365R) does not suppress the basal activity of certain promoters containing thyroid hormone response elements, suggesting that this silencing effect of T3R is mediated by unliganded heterodimers of T3R and endogenous RXR or related factors. Heterodimerization is also necessary for the strong ligand-independent inhibition between T3R and RAR on a common response element, since the ninth-heptad mutants function as poor inhibitors. However, with a T3R-specific response element, hRAR(M377R) acts as a retinoic acid-dependent inhibitor of cT3R, indicating the importance of heterodimerization for this inhibition. Our studies also suggest that the ninth heptad is necessary for the dominant inhibition of wild-type T3Rs by mutant T3Rs, as has been found for the thyroid hormone-resistant syndrome in humans. Thus, the ninth heptad repeat is required for heterodimerization, suppression of basal promoter activity, and dominant negative effects of T3R and RAR. Lastly, the finding that cT3R(L365R) and hRAR(M377R) require ligands for heterodimer formation also raises the possibility that heterodimeric interactions are mediated by the ninth heptad without ligands but by a second region of these receptors with ligands.
Non-SELEX Selection of Aptamers (2006)

Aptamers are typically selected from libraries of random DNA (or RNA) sequences by SELEX, which involves multiple rounds of alternating steps of partitioning and PCR amplification. Here we report, for the first time, non-SELEX selection of aptamers-a process that involves repetitive steps of partitioning with no amplification between them. A highly efficient affinity method, non-equilibrium capillary electrophoresis of equilibrium mixtures (NECEEM), was used for partitioning. We found that three steps of NECEEM-based partitioning in the non-SELEX approach were sufficient to improve the affinity of a DNA library to a target protein by more than 4 orders of magnitude. The resulting affinity was higher than that of the enriched library obtained in three rounds of NECEEM-based SELEX. Remarkably, NECEEM-based non-SELEX selection took only 1 h in contrast to several days or several weeks required for a typical SELEX procedure by conventional partitioning methods. In addition, NECEEM-based non-SELEX allowed us to accurately measure the abundance of aptamers in the library. Not only does this work introduce an extremely fast and economical method for aptamer selection, but it also suggests that aptamers may be much more abundant than they are thought to be. Finally, this work opens the opportunity for selection of drug candidates from libraries of small molecules, which cannot be PCR-amplified and thus are not approachable by SELEX.
Bacterial d-amino acid oxidases: Recent findings and future perspectives (2015)

D-Amino acid oxidase (DAO) is a flavin enzyme that catalyzes the oxidative deamination of d-amino acids. This enzyme has been studied extensively both biochemically and structurally as a model for the oxidase-dehydrogenase class of flavoproteins. This enzyme also has various applications, such as the determination of d-amino acids and production of building blocks for a number of pharmaceuticals. DAO has been found mainly in eukaryotic organisms and has been suggested to play a significant role in various cellular processes, one of which includes neurotransmission in the human brain. In contrast, this enzyme has not been identified in prokaryotic organisms. Some studies have recently identified and characterized DAO enzyme in some actinobacteria. In addition, a genome database search reveals a wide distribution of DAO homologous genes in this bacterial group. The bacterial DAOs characterized so far have certain distinct properties in comparison to eukaryotic DAOs. These enzymes also exhibit some important applicable properties, suggesting that bacteria could be used as a source for obtaining novel and useful DAOs. The physiological function of bacterial DAO have been proposed to include the degradation of non-canonical d-amino acids released from cell wall, but is still largely unknown and need to be studied in depth.
Monolithically Integrated Corporate-Fed Cavity-Backed Antennas (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> A <emphasis emphasistype="italic">Ka</emphasis>-band monolithically integrated 4<formula formulatype="inline"><tex Notation="TeX">$\,\times\,$</tex> </formula>1 corporate-fed cavity-backed patch antenna array is demonstrated in this paper. A single antenna element has four slits introduced to extend the bandwidth to about 8%. Its gain and radiation efficiency are 6.3 dBi and 97%, respectively. A rectangular <formula formulatype="inline"><tex Notation="TeX">$\mu$</tex> </formula>-coaxial line based combining network is monolithically integrated with radiating elements in a slightly modified tile configuration. Specifically, to reduce the array footprint power dividers are aligned along the array axis. Combining network has height 1/2 that of the array and feed lines do not route through the antenna elements. Overall loss of the combining network is 0.5 dB at 30 GHz. Measured reflection coefficient bandwidth and maximum gain of the fabricated 4<formula formulatype="inline"><tex Notation="TeX">$\,\times\,$</tex> </formula>1 corporate-fed array are 13.7% and 12.73 dBi, respectively. The array is designed and fabricated in a recently developed surface micromachining process known as PolyStrata. </para>
High-visibility interference in a Bell-inequality experiment for energy and time (1993)

We report on a two-photon interference experiment proposed by Franson [Phys. Rev. Lett. 62, 2205 (1989)], in which sinusoidal fringes with visibilities greater than 70.7%, such as those predicted by quantum mechanics, violate a Bell inequality. We observe visibility of 80.4\ifmmode\pm\else\textpm\fi{}0.6%, implying a violation of the inequality by 16 standard deviations. Here the elements of reality under consideration are energy and time rather than spin components. Any classical field models describing separate beams in a Franson interferometer are limited to visibilities less than 50%, and hence ruled out as well, without the need for any supplementary assumptions.
Flexible hydroxyapatite ultralong nanowire-based paper for highly efficient and multifunctional air filtration (2017)

Ultralong hydroxyapatite nanowire-based air filter paper with a low pressure drop and high removal efficiencies for PM<sub>2.5</sub> and PM<sub>10</sub> has been developed.
Protein Meta-Functional Signatures from Combining Sequence, Structure, Evolution, and Amino Acid Property Information (2008)

Protein function is mediated by different amino acid residues, both their positions and types, in a protein sequence. Some amino acids are responsible for the stability or overall shape of the protein, playing an indirect role in protein function. Others play a functionally important role as part of active or binding sites of the protein. For a given protein sequence, the residues and their degree of functional importance can be thought of as a signature representing the function of the protein. We have developed a combination of knowledge- and biophysics-based function prediction approaches to elucidate the relationships between the structural and the functional roles of individual residues and positions. Such a meta-functional signature (MFS), which is a collection of continuous values representing the functional significance of each residue in a protein, may be used to study proteins of known function in greater detail and to aid in experimental characterization of proteins of unknown function. We demonstrate the superior performance of MFS in predicting protein functional sites and also present four real-world examples to apply MFS in a wide range of settings to elucidate protein sequence-structure-function relationships. Our results indicate that the MFS approach, which can combine multiple sources of information and also give biological interpretation to each component, greatly facilitates the understanding and characterization of protein function.
Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. (1994)

The gene mutated in the human disease, X-linked agammaglobulinemia (XLA), is related to the Src gene family of cytoplasmic protein-tyrosine kinases and is designated Btk (Bruton's agammaglobulinemia tyrosine kinase; formerly Atk/Bpk; the human gene is denoted BTK, using capital letters according to the kinase nomenclature). We have recently reported that this gene is expressed in B lymphocytes and that the specific mRNA was undetectable in T cells using Northern blotting. Further analyses of different sources of B and T lymphocytes confirmed this pattern. However, BTK transcripts were undetectable in four plasmacytoma lines. Moreover, as virtually normal amounts of BTK transcripts were found in PBMC from two patients carrying a point mutation in BTK, despite low B cell numbers, we anticipated that the gene would also be expressed in cells of other lineages. The erythroleukemia cell line K-562, the promyelocytic line HL-60 and the histiocytic lymphoma line U-937 were found to have BTK mRNA levels comparable to B cells. BTK mRNA was also detected in monocytes from healthy donors as well as in the human immature basophilic cell line KU812, in the human mast cell leukemia cell line HMC-1 and in the CD34 expressing myeloblast KG-1. A similar expression pattern was obtained when BTK protein was analyzed by immunoprecipitation and Western blotting. Using a polymerase chain reaction-based analysis, a small amount (less than 1% of the level in B cells) of BTK mRNA was identified in T lymphocytes. Our findings are compatible with a general expression of the BTK gene in hematopoietic cells, except in T lymphocytes and plasma cells, in which the transcript level is selectively down-regulated.
Multiple-Cytokine-Producing Antiviral CD4 T Cells Are Functionally Superior to Single-Cytokine-Producing Cells (2007)

Virus-specific CD4 T cells are endowed with multiple functions, such as cytokine production, CD40 ligand (CD40L) expression (associated with the costimulation of CD8 and B cells), and degranulation (associated with cytotoxic potential). Here, we used antiviral CD4 T cells present in human blood to evaluate the relationship between cytokine production and other functions of CD4 T cells. Antiviral CD4 T cells specific for a virus causing persistent infection, cytomegalovirus (CMV), and two viruses causing nonpersistent infections, influenza virus and the smallpox vaccine virus (vaccinia virus), were studied. CD4 T cells specific for each of the viruses produced all seven possible combinations of the cytokines gamma interferon (IFN-gamma), interleukin-2, and tumor necrosis factor alpha. Cells producing three or two cytokines (triple producers and double producers) represented nearly 50% of the total response to each of the viruses. Triple producers expressed the highest levels of cytokines per cell, and single producers expressed the lowest. Following stimulation, higher frequencies of triple producers than single producers expressed CD40L. Only CMV-specific CD4 T cells underwent degranulation. However, higher frequencies of CMV-specific triple producers than single producers showed this functional characteristic. In contrast to the functional phenotypes, the memory phenotypes of triple producers and IFN-gamma single producers did not differ. These results demonstrate a strong positive association between the cytokine coproduction capacity of a virus-specific CD4 T cell and its other functional characteristics and suggest that vaccines should aim to elicit T cells that coproduce more than one cytokine.
Human neutrophils secrete vascular endothelial growth factor (1997)

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a pivotal role in mediating neovascularization as well as other endothelial cell alterations during inflammation. In this study, we demonstrate that human neutrophils are a source of VEGF. We observed that isolated blood neutrophils released VEGF in response to different stimuli and we demonstrated by immunohistochemistry that neutrophils infiltrating inflamed tissues contain VEGF. These results indicate that neutrophil-derived VEGF may be instrumental in regulating vascular responses during acute and chronic inflammation.
Fermentative Metabolism of Chlamydomonas reinhardtii (1984)

The anaerobic starch breakdown into end-products in the green alga Chlamydomonas reinhardtii F-60 has been investigated in the dark and in the light. The effects of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) on the fermentation in the light have also been investigated.Anaerobic starch breakdown rate (13.1 +/- 3.5 micromoles C per milligram chlorophyll per hour) is increased 2-fold by FCCP in the dark. Light (100 watts per square meter) decreases up to 4-fold the dark rate, an inhibition reversed by FCCP. Stimulation of starch breakdown by the proton ionophore FCCP points to a pH-controlled rate-limiting step in the dark, while inhibition by light, and its reversal by FCCP, indicates a control by energy charge in the light.In the dark, formate, acetate, and ethanol are formed in the ratios of 2.07:1.07:0.91, and account for roughly 100% of the C from the starch. H(2) production is 0.43 mole per mole glucose in the starch. Glycerol, d-lactate, and CO(2) have been detected in minor amounts.In the light, with DCMU and FCCP present, acetate is produced in a 1:1 ratio to formate, and H(2) evolution is 2.13 moles per mole glucose. When FCCP only is present, acetate production is lower, and CO(2) and H(2) evolution is 1.60 and 4.73 moles per mole glucose, respectively.When DCMU alone is present, CO(2) and H(2) photoevolution is higher than in the dark. Without DCMU, CO(2) and H(2) evolution is about 100% higher than in its presence. In both conditions, acetate is not formed. In all conditions in the light, ethanol is a minor product. Formate production is least affected by light.The stoichiometry in the dark indicates that starch is degraded via the glycolytic pathway, and pyruvate is broken down into acetyl-CoA and formate. Acetyl-CoA is further dissimilated into acetate and ethanol. In the light, acetate is produced only in the presence of FCCP and, when photophosphorylation is possible, it is used in unidentified reactions. Ethanol formation is inhibited by the light in all conditions.
Protection of rabbits against experimental pasteurellosis by a streptomycin-dependent Pasteurella multocida serotype 3:A live mutant vaccine (1981)

Pasteurella multocida (serotype 3:A) was isolated from a rabbit with clinical signs of suppurative rhinitis. This P. multocida strain was mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine to obtain a genetically stable streptomycin-dependent mutant, from which a life vaccine was prepared. Pasteurella-free rabbits were inoculated intranasally three times at weekly intervals and challenged intranasally with a virulent serotype 3:A rabbit P. multocida isolate 2 weeks after the third vaccination. The rabbits were killed 2 to 3 weeks later. The vaccine did not cause clinical disease, death, or gross or microscopic lesions. Furthermore, the vaccine protected the challenge rabbits from developing clinical disease, death, and gross lesions. However, mild focal lung lesions were noted in several of the vaccinated-challenged animals. In contrast, nonvaccinated-challenged rabbits developed pyrexia and anorexia. Furthermore, three of four of these rabbits died with severe gross lesions including pyothorax, suppurative pericarditis, and fibrinopurulent pneumonia. Microscopically, the four nonvaccinated rabbits had moderate to severe suppurative pneumonia and mild to moderate suppurative rhinitis, and two had mild tympanitis. The mutant vaccine did not appear to colonize the nasal cavities. The vaccine prevented the colonization of the virulent challenge organism in lungs, liver, spleen, genital tracts, and blood, but not the nasal cavities.
METHYLPREDNISOLONE REVERSES VASOPRESSIN HYPORESPONSIVENESS IN OVINE ENDOTOXEMIA (2007)

Tachyphylaxis against catecholamines often complicates hemodynamic support in patients with septic shock. Recent experimental and clinical research suggests that the hemodynamic response to exogenous arginine vasopressin (AVP) infusion may also be blunted. The purpose of the present study was therefore to clarify whether the efficacy of a continuous AVP infusion (0.04 U x min(-1)) decreases over time in ovine endotoxemia. An additional objective was to determine whether the anticipated hyporesponsiveness can be counteracted by corticosteroids. Fourteen adult ewes (37 +/- 1 kg) were instrumented for chronic hemodynamic monitoring. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation. After 16 h of endotoxemia, the sheep were randomized to receive either AVP (0.04 U x min(-1)) or the vehicle (normal saline; n = 7 each). After 6 h of AVP or placebo infusion, respectively, methylprednisolone (30 mg x kg(-1)) was injected. Arginine vasopressin infusion increased mean arterial pressure and systemic vascular resistance index at the expense of a reduced cardiac index (P < 0.05 each). Supraphysiologic AVP plasma levels in the treatment group (298 +/- 15 pg x mL(-1)) were associated with increased surrogate parameters of liver, mesenterial, and myocardial dysfunction. After 6 h of continuous AVP infusion, the vasopressor effect was significantly reduced. Interestingly, a bolus infusion of methylprednisolone (30 mg x kg(-1)) reestablished mean arterial pressure by increasing both cardiac index and systemic vascular resistance index. The present study demonstrates that in endotoxemia, (a) the vasopressor effect of AVP infusion may be reduced, (b) corticosteroids may potentially be useful to increase the efficacy of AVP infusion, and (c) even moderate AVP doses may potentially impair myocardial and hepatic function.