gebhart/patrepeval huggingface dataset:
Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide (2000)

Nitric oxide (NO) regulates production of vascular endothelial growth factor (VEGF) by normal and transformed cells. We demonstrate that NO donors may up-regulate the activity of the human VEGF promoter in normoxic human glioblastoma and hepatoma cells independent of a cyclic guanosine monophosphate-mediated pathway. Deletion and mutation analysis of the VEGF promoter indicates that the NO-responsive cis-elements are the hypoxia-inducible factor-1 (HIF-1) binding site and an adjacent ancillary sequence that is located immediately downstream within the hypoxia-response element (HRE). This work demonstrates that the HRE of this promoter is the primary target of NO. In addition, VEGF gene regulation by NO, as well as by hypoxia, is potentiated by the AP-1 element of the gene. Our study also reveals that NO and hypoxia induce an increase in HIF-1 binding activity and HIF-1alpha protein levels, both in the nucleus and the whole cell. These results suggest that there are common features of the NO and hypoxic pathways of VEGF induction, while in part, NO mediates gene transcription by a mechanism distinct from hypoxia. This is demonstrated by a difference in sensitivity to guanylate cyclase inhibitors and a different pattern of HIF-1 binding. These results show that there is a primary role for NO in the control of VEGF synthesis and in cell adaptations to hypoxia. (Blood. 2000;95:189-197)
PCs for AP (1988)

The focus of this column will be the general subject of "visualization" and how computers and computer graphics are revolutionizing this fascinating area. Over the past few years, including the occasion of a course I gave at Kansas University on developing computer-graphics movies for teaching, I have collected a number of books related in one way or another to visualization and graphics. During that collection process I was surprised to find myself perusing the art and medical departments of book stores as I discovered that my evolving interest in visualization naturally led to investigating how artists, who specialize in presenting visual images, deal with that problem from a mental viewpoint. This led to another unexpected topic, that of psychology, and in particular how we interpret what we see. I thought that it might be useful to present summaries of several otf he more interestingt o me, and I hope to you also. You should be warned that this will be a rather eclectic book collection asa ll are not directly relatetdo computer graphics,b ut do relate to visualization in one form or another
Passive vs. closed suction drainage after perineal wound closure following abdominoperineal rectal excision for carcinoma (1995)

These results suggest that closed suction drainage should be used after abdominoperineal rectal excision with satisfactory hemostasis or absence of gross introperative septic contamination.
Synthesis and Characterization of Some Aza[5]helicenes (2005)

Abstract A systematic study on the synthesis and properties of aza‐[5]helicenes bearing one or two nitrogen atoms in selected ring positions is reported for the first time. This photochemical approach can be conveniently applied to the preparation of either mono‐ or diaza[5]helicenes. The aza[5]helicenes were characterized by NMR spectroscopy, X‐ray crystallography, emission spectroscopy, and luminescence lifetime. The extremely long triplet lifetime observed (in the range of seconds) makes these molecules promising candidates for practical applications in photo‐ and optoelectronics. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Monitoring unfractionated heparin with the aPTT: Time for a fresh look (2006)

Laboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range. The most widely used laboratory assay for monitoring unfractionated heparin therapy is the activated partial thromboplastin time (aPTT). A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted, but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable. The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment. Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations, the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test. The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized. Future research efforts should be directed towards developing methods to improve standardization of the aPTT assay for monitoring unfractionated heparin. Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation. However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies.
Adhesion receptors are differentially expressed on developing thymocytes and epithelium in human thymus. (1992)

The thymic microenvironment consists of a network of interrelated cells of epithelial, fibroblastic, endothelial, and hemopoietic origin. Within this environment, the development of specific T-lymphocyte subpopulations partially depends on the selective interaction of T-cell precursors with such cells. Human thymic epithelial cell strains, generated with a defective retroviral vector containing simian virus 40 (SV40) large T antigen and the neomycin resistance gene or by transfection with an SV40 plasmid defective in the origin of replication, provide useful tools for understanding the mechanisms contributing to the control of T-cell maturation. Because interepithelial, epithelial-macrophage, and lymphocyte-epithelial cell interactions are important for thymocyte differentiation, the distribution of integrin and nonintegrin adhesion receptors on these cells and on developing thymocytes in vivo and in vitro has been examined in detail. Our results indicate that the transformed human thymic epithelial cell strains express the common very late antigen (VLA)-beta 1 receptor and unique alpha chains VLA-2, VLA-3, and VLA-6. The cells are also positive for LFA-3 and ICAM-1 and weakly express beta 3, beta 4, and VNR alpha. They do not express the Leu-cellular adhesion molecules (CAM). This phenotypic profile on cultured thymic epithelium generally corresponds to the distribution of integrin and other receptor molecules on thymic epithelial cells in tissue sections. The majority of thymocytes also express the integrin VLA-beta 1 and -beta 2 chains as well as VLA-4, VLA-6, and LFA-1 alpha(L). Three-color flow cytometric analyses show differential levels of expression of these adhesion receptors on human thymocyte subsets. Taken together with the immunohistochemical localization of extracellular matrix molecules, these studies suggest that both the distribution of receptor-ligand pairs and the level of expression of adhesion molecules may influence T-cell development within the thymus.
Broadband fiber optic hydrophone sensors for sub-millimeter ultrasound resolutions (2008)

Broadband fiber optic hydrophone probes are an attractive solution for characterization of ultrasound fields with sub-millimeter resolution up to 100 MHz frequency range without need for complicated spatial averaging corrections. In this work, optical hydrophone sensors based on single mode straight - cleaved fibers and down-tapered coated fibers with sensitive dimensions of less than 10 mum have been reported. Thinly gold coated optical fiber sensors demonstrated a higher sensitivity and bandwidth performance than straight cleaved uncoated and down-tapered uncoated. The statistical analysis clearly indicates that the gold coated fibers with thickness of 30 nm provide a 26 dB improvement in sensitivity over that of the uncoated straight cleaved fibers, raising the overall sensitivity of the fiber optic hydrophone sensor to a value of -245 dB re 1 V /muPa (unprecedented 0.56 V/ MPa). Broadband testing of these sensors with a 10 MHz acoustic tone burst further indicates that the bandwidth of gold coated fiber sensor is as high as 60 MHz. Amplified optical source intensity noise limits the current intensity detection system up to 60 MHz.
Carbon Monoxide Inhibits T Lymphocyte Proliferation via Caspase-Dependent Pathway (2004)

T lymphocyte activation and proliferation is involved in many pathological processes. We have recently shown that carbon monoxide (CO), an enzymatic product of heme oxygenase-1 (HO-1), confers potent antiproliferative effects in airway and vascular smooth muscle cells. The purpose of this study was to determine whether CO can inhibit T lymphocyte proliferation and then to determine the mechanism by which CO can modulate T lymphocyte proliferation. In the presence of 250 parts per million CO, CD3-activated T lymphocyte proliferation was, remarkably, inhibited by 80% when compared with controls. We observed that the antiproliferative effect of CO in T lymphocytes was independent of the mitogen-activated protein kinase or cGMP signaling pathways, unlike what we demonstrated previously in smooth muscle cells. We demonstrate that CO inhibited caspase-3 and caspase-8 expression and activity, and caspase inhibition with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK pan-caspase inhibitor) blocked T lymphocyte proliferation. Furthermore, in caspase-8-deficient lymphocytes, the antiproliferative effect of CO was markedly attenuated, further supporting the involvement of caspase-8 in the antiproliferative effects of CO. CO also increased the protein level of p21(Cip1), and CO-mediated inhibition of caspase activity is partially regulated by p21(Cip1). Taken together, these data suggest that CO confers potent antiproliferative effects in CD3-activated T lymphocytes and that these antiproliferative effects in T lymphocytes are mediated by p21(Cip1)-dependent caspase activity, in particular caspase-8, independent of cGMP and mitogen-activated protein kinase signaling pathways.
R391: a Conjugative Integrating Mosaic Comprised of Phage, Plasmid, and Transposon Elements (2002)

The conjugative, chromosomally integrating element R391 is the archetype of the IncJ class of mobile genetic elements. Originally found in a South African Providencia rettgeri strain, R391 carries antibiotic and mercury resistance traits, as well as genes involved in mutagenic DNA repair. While initially described as a plasmid, R391 has subsequently been shown to be integrated into the bacterial chromosome, employing a phage-like integration mechanism closely related to that of the SXT element from Vibrio cholerae O139. Analysis of the complete 89-kb nucleotide sequence of R391 has revealed a mosaic structure consisting of elements originating in bacteriophages and plasmids and of transposable elements. A total of 96 open reading frames were identified; of these, 30 could not be assigned a function. Sequence similarity suggests a relationship of large sections of R391 to sequences from Salmonella, in particular those corresponding to the putative conjugative transfer proteins, which are related to the IncHI1 plasmid R27. A composite transposon carrying the kanamycin resistance gene and a novel insertion element were identified. Challenging the previous assumption that IncJ elements are plasmids, no plasmid replicon was identified on R391, suggesting that they cannot replicate autonomously.
Characterization of two genes encoding distinct transferrin-binding proteins in different Actinobacillus pleuropneumoniae isolates (1992)

The gene encoding the Actinobacillus pleuropneumoniae serotype 1 transferrin-binding protein (tfbA) was cloned, and the carboxy-terminal 70% of the protein was expressed as an aggregate protein in Escherichia coli. The nucleotide sequences of the tfbA genes from A. pleuropneumoniae serotypes 7 (G.-F. Gerlach, C. Anderson, A. A. Potter, S. Klashinsky, and P. J. Willson, Infect. Immun. 60:892-898, 1992) and 1 were determined, and a comparison revealed that they had 65% sequence identity. The deduced amino acid sequences showed a sequence agreement of 55%, and both proteins possessed a lipoprotein-like signal sequence. The serotype 1 TfbA protein had a predicted molecular mass of 65 kDa, compared with 60 kDa for the serotype 7 TfbA protein, and both proteins were immunologically distinct as assessed in a competitive enzyme-linked immunosorbent assay. Southern hybridization and Western blot (immunoblot) analysis of the 13 A. pleuropneumoniae type strains revealed that serotypes 2, 3, 4, 8, 9, 10, and 11 encode and express a TfbA protein highly homologous to that of A. pleuropneumoniae serotype 7 whereas the TfbA proteins and the encoding genes of serotypes 6 and 12 were highly homologous to that found in A. pleuropneumoniae serotype 1. The tfbA genes of A. pleuropneumoniae serotypes 5A and 5B were recognized, under medium-stringency hybridization conditions, by the A. pleuropneumoniae serotype 1-derived tfbA probe, and the respective proteins were weakly reactive with the antibody raised against the A. pleuropneumoniae serotype 7 TfbA protein.
Combinatorial Library Methods and Protocols (2002)

By significantly increasing the number of targets available for drug discovery, the Human Genome and Proteome projects have made the use of combinatorial libraries essential to developing and optimizing drug candidate molecules more rapidly. Lisa English and a panel of expert researchers have collected in Combinatorial Library Methods and Protocols a novel series of computational and laboratory methods for the design, synthesis, quality control, screening, and purification of combinatorial libraries. Here the reader will find cutting-edge techniques for the preparation of encoded combinatorial libraries, for the synthesis of DNA-binding polyamides, and for combinatorial receptors. There are also state-of-the-art methods for computational library design, quality control by mass spectrometry, and structure verification using 1D and 2D NMR. A variety of well-known computational approaches are provided to meet the information management challenge of multiple biological assays. Each readily reproducible technique includes detailed step-by-step instructions and helpful notes on troubleshooting and avoiding pitfalls. Timely and highly practical, Combinatorial Library Methods and Protocols makes available for all drug discovery researchers all the powerful combinatorial chemistry tools that are increasing the number of candidate compounds and speeding the process of drug discovery and development today
Routine Multiplex Mutational Profiling of Melanomas Enables Enrollment in Genotype-Driven Therapeutic Trials (2012)

We present development of a simple mutational profiling screen for clinically relevant mutations in melanoma. Adoption of this genetically-informed approach to the treatment of melanoma has already had an impact on clinical trial enrollment and prioritization of therapy for patients with the disease.
Circularly Polarized Electroluminescence from a Polymer Light-Emitting Diode (1997)

An example is presented of circularly polarized electroluminescence (CPEL) of a polymer LED which is constructed using a chiral p-conjugated poly(p-phenylenevinylene) (PPV) deriv. as an active layer. The CPEL is a direct consequence of the intrinsic mol. chirality of the conjugated polymer and requires no macroscopic orientation of chromophores as for linear polarized electroluminescence.
Selective antagonism of capsaicin by capsazepine: evidence for a spinal receptor site in capsaicin‐induced antinociception (1991)

1. Capsazepine has recently been described as a competitive capsaicin antagonist. We have used this compound to test the hypotheses that the in vitro and in vivo effects of capsaicin are due to interactions with a specific receptor. 2. In an in vitro preparation of the neonatal rat spinal cord with functionally connected tail, the activation of nociceptive afferent fibres by the application of capsaicin, bradykinin or noxious heat (48 degrees C) to the tail could be measured by recording a depolarizing response from a spinal ventral root. Application of capsaicin or substance P to the spinal cord also evoked a depolarizing response which was recorded in a ventral root. 3. When capsazepine (50 nM-20 microM) was administered to the tail or spinal cord it did not evoke any measurable response. However on the tail, capsazepine reversibly antagonized (IC50 = 254 +/- 28 nM) the responses to capsaicin but not to heat or bradykinin administered to the same site. Similarly capsazepine administration to the spinal cord antagonized the responses evoked by capsaicin (IC50 = 230 +/- 20 nM) applied to the cord but not responses evoked by substance P on the cord or by noxious heat and capsaicin on the tail. 4. In halothane anaesthetized rats, C-fibre responses evoked by transcutaneous electrical stimulation of the receptive field were recorded from single wide dynamic range neurones located in the spinal dorsal horn. C-fibre evoked discharges were consistently reduced by the systemic administration of capsaicin (20 mumol kg-1, s.c.) and this action of capsaicin was antagonized by capsazepine (100 mumol kg-1) administered by the same route. In addition the systemic effect of capsaicin was antagonized by a spinal intrathecal administration of capsazepine (5-50 nmol). 5. Intradermal injections of capsaicin, localized to the peripheral receptive field, usually one toe of the ipsilateral hind-paw, produced a transient increase in C-fibre-evoked activity followed by a prolonged period of localized insensitivity to transcutaneous C-fibre stimulation. These effects of capsaicin were significantly reduced by the concommitant administration of capsazepine to the same site. 6. These data demonstrate that capsazepine is a selective antagonist of capsaicin on nociceptive neurones in vitro and in vivo and suggest that the effects of capsaicin were mediated by activation of a specific receptor. Since the antinociceptive effect produced by systemically administered capsaicin was antagonised by spinal intrathecal capsazepine this further supports the hypothesis that capsaicin exerts its antinociceptive effect by acting on specific receptors localized to sensory nerve fibres in the spinal cord.
Structure determination and refinement of homotetrameric hemoglobin from Urechis caupo at 2.5 Å resolution (1992)

A 5 A resolution multiple isomorphous replacement solution for hemoglobin isolated from Urechis caupo revealed a previously unobserved quaternary structure for tetrameric hemoglobin [Kolatkar, Meador, Stanfield & Hackert (1988). J. Biol. Chem. 263(7), 3462-3465]. We report here the structure of Urechis hemoglobin in the cyanomet state refined to 2.5 A resolution by simulated annealing yielding R = 0.148 for reflections F greater than 3 sigma between 5.0 and 2.5 A resolution. The starting model was fitted to a map originally derived from multiple-wavelength anomalous-dispersion phases to 3 A resolution that was then subjected to cyclic twofold molecular averaging and solvent flattening. Structural analysis of the resultant model shows that the unique quaternary assemblage is possible due to several favorable interactions between subunits, including salt links, hydrophobic pockets and interactions mediated by bound water. The tetramer is stabilized by subunit-subunit interactions between the G/H turns and D helices within the crystallographic dimer, and the A/B turn regions and E helices between subunits related by a molecular twofold axis. Interestingly, each subunit has one cysteine residue (Cys21) located in the A/B turn. These twofold-related cysteinyl residues are near enough to one another to form a disulfide bridge but do not.
A 1-MW, 1-mm continuous-wave FELtron for toroidal plasma heating (1992)

A powerful, continuous-wave millimeter radiation source is presented. An electrostatic Cockcroft-Walton accelerator (2.5 MV) drives an FEL (free-electron laser) of 1 MW power. The accelerator has a new design in order to obtain a very powerful (50 MW) electron beam and very small ripple. A recovery system is used to increase RF power and efficiency. The FEL oscillator is 1.5-m long, with a permanent magnet helical wiggler. The cavity is equipped with Bragg mirrors. The FEL is set at the high voltage terminal.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Comparative sequence analysis of the reovirus S4 genes from 13 serotype 1 and serotype 3 field isolates (1995)

The reovirus sigma 3 protein is a major outer capsid protein that may function to regulate translation within infected cells. To facilitate the understanding of sigma 3 structure and functions and the evolution of mammalian reoviruses, we sequenced cDNA copies of the S4 genes from 10 serotype 3 and 3 serotype 1 reovirus field isolates and compared these sequences with sequences of prototypic strains of the three reovirus serotypes. We found that the sigma 3 proteins are highly conserved: the two longest conserved regions contain motifs proposed to function in binding zinc and double-stranded RNA. We used the 16 viral isolates to investigate the hypothesis that structural interactions between sigma 3 and the cell attachment protein, sigma 1, constrain their evolution and to identify a determinant within sigma 3 that is in close proximity to the sigma 1 hemagglutination site.
LOCATE: a mammalian protein subcellular localization database (2007)

LOCATE is a curated, web-accessible database that houses data describing the membrane organization and subcellular localization of mouse and human proteins. Over the past 2 years, the data in LOCATE have grown substantially. The database now contains high-quality localization data for 20% of the mouse proteome and general localization annotation for nearly 36% of the mouse proteome. The proteome annotated in LOCATE is from the RIKEN FANTOM Consortium Isoform Protein Sequence sets which contains 58 128 mouse and 64 637 human protein isoforms. Other additions include computational subcellular localization predictions, automated computational classification of experimental localization image data, prediction of protein sorting signals and third party submission of literature data. Collectively, this database provides localization proteome for individual subcellular compartments that will underpin future systematic investigations of these regions. It is available at http://locate.imb.uq.edu.au/