1,340 research outputs found

    Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

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    Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors

    Flight path analysis in sounding rocket “Libertador I” with computational simulation on three degrees of freedom

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    This paper presents obtained results from computer simulations in order to analyze the flight path of the sounding rocket Libertador I, developed in 2012 at the Fundación Universitaria Los Libertadores. The main aspects that affect the motion of a rocket are propulsion and aerodynamics effects. Numerical algorithms were implemented to value the thrust provided by the rocket motor as well as aerodynamic loads. Then, the differential equations of the motion are solved using the Runge-Kutta method, RK9. Trajectory and other numerical results are calculated from a code developed in FORTRAN. Finally, graphs of the flight path, curves of the vehicle velocity as function of time are presented. Also, the algorithm permits to determine the maximum altitude and possible impact sites.Facultad de Ingenierí

    A Structural Parametrization of the Brain Using Hidden Markov Models Based Paths in Alzheimer's Disease

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    The usage of biomedical imaging in the diagnosis of dementia is increasingly widespread. A number of works explore the possibilities of computational techniques and algorithms in what is called Computed Aided Diagnosis. Our work presents an automatic parametrization of the brain structure by means of a path generation algorithm based on Hidden Markov Models. The path is traced using information of intensity and spatial orientation in each node, adapting to the structural changes of the brain. Each path is itself a useful way to extract features from the MRI image, being the intensity levels at each node the most straightforward. However, a further processing consisting of a modification of the Gray Level Co-occurrence Matrix can be used to characterize the textural changes that occur throughout the path, yielding more meaningful values that could be associated to the structural changes in Alzheimer's Disease, as well as providing a significant feature reduction. This methodology achieves high performance, up to 80.3\% of accuracy using a single path in differential diagnosis involving Alzheimer-affected subjects versus controls belonging to the Alzheimer's Disease Neuroimaging Initiative (ADNI).TIC218, MINECO TEC2008-02113 and TEC2012-34306 projects, Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía P09-TIC-4530 and P11-TIC-71

    Flight path analysis in sounding rocket “Libertador I” with computational simulation on three degrees of freedom

    Get PDF
    This paper presents obtained results from computer simulations in order to analyze the flight path of the sounding rocket Libertador I, developed in 2012 at the Fundación Universitaria Los Libertadores. The main aspects that affect the motion of a rocket are propulsion and aerodynamics effects. Numerical algorithms were implemented to value the thrust provided by the rocket motor as well as aerodynamic loads. Then, the differential equations of the motion are solved using the Runge-Kutta method, RK9. Trajectory and other numerical results are calculated from a code developed in FORTRAN. Finally, graphs of the flight path, curves of the vehicle velocity as function of time are presented. Also, the algorithm permits to determine the maximum altitude and possible impact sites.Facultad de Ingenierí

    Community structure and height distribution of intertidal rockpool fish in Los Cóbanos, El Salvador

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    Tide cycles determine the ecological complexity and environmental dynamics observed in the intertidal habitats. Intertidal dwellers show particular patterns of distribution with abrupt changes even at distances of few meters. Tropical intertidal zones have seldom been studied; therefore the community structure and vertical distribution of the intertidal rockpool fish of Los Cóbanos was assessed. In the intertidal zone, a total of 18 rockpools were selected according to the shore height as low (3-39 cm), mid (40-75 cm) and high (76-110 cm), with 6 replicate rockpools per shore level. Physico-chemical variables (temperature, salinity, pH), substratum homogeneity (algal, sand and rock cover) and habitat complexity were measured and rockpools were sampled every three months for one year. Overall, the intertidal assemblage of rockpool fish was composed of 48 species and dominated in abundance and species richness by the families Gobiidae (4 species and 746 fish or 31.29%) and Pomacentridae (5 species, 546 fish or 22.90%). The most abundant species were Bathygobius ramosus (27.76%) and Stegastes acapulcoensis (11.07%). Juvenile fish (75%) were more abundant than adults and larvae. Opportunist fishes were more abundant than permanent residents and transients comprising 58.53%, 39.87% and 1.6% of the abundance, respectively. Intertidal height, volume and rock cover were the most important variables that determined changes in the community structure. Six species presented size class segregation among rockpools at shore heights in the intertidal zone

    Alcohol drinking and low nutritional value food eating behavior of sports bettors in gambling advertisements

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    The prevalence of sports betting advertising has become a major concern for gambling regulators, particularly since the legalization of online gambling in many European jurisdictions. Although the composition of gambling advertisement narratives has received some limited attention, nothing is known regarding how betting advertisements (often referred to as “adverts” or “commercials”) might be associating gambling with other potentially risky behaviors. The present paper examines the representation of alcohol drinking and low nutritional value food eating in sports betting advertising. By means of a mixed-methods approach to content analysis, a sample of British and Spanish soccer betting adverts was analyzed (N = 135). The results suggest that betting advertising aligns drinking alcohol with sports culture and significantly associates emotionally charged sporting situations such as watching live games or celebrating goals with alcohol. Additionally, alcohol drinking is more frequent in betting adverts with a higher number of characters, linking friendship bonding and alcohol drinking (especially beer) in the context of sports gambling

    Endless forms most hidden: katydids that masquerade as moss

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    In the cloud forests of the central range of the Colombian Andes, we discovered a species of katydid (Orthoptera: Tettigoniidae) that imitates mosses to an uncanny degree and is exceedingly difficult to detect. The camouflage exhibited by this particular katydid seems quite specific. We discuss the evolutionary consequences of this sort of specialization. Selection to maintain effective disguises can result in reproductive isolation between populations specialized for different microhabitats, which makes it reasonable to speculate that camouflage may increasing diversification rates. Camouflage could also come at the price of elevated extinction risk. This possibility must be considered because although antipredator defenses are often thought of as leading to “escape-and-radiate” dynamics where diversification follows innovation that allows expansion into new niches, recent work has shown unexpected extinction risk associated with some antipredator adaptations. Highly specialized camouflage would seem an ambiguous case because of its obvious benefits, but also potential costs such as inhabiting habitats with low carrying capacities, vulnerability to predators at high densities if predators form search images, or metabolic trade-offs with thermoregulation. Groups such as the Tettigoniidae provide a tantalizing opportunity for their exceptional diversity, wide geographic distribution, and striking array of disguises suggest that many independent evolutionary experiments have already taken place

    Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

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    During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregu- lated at high AP frequencies to balance SV consumption. We show that Munc13-1—an essential SV priming protein—regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotrans- mission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

    Luxación recidivante de prótesis total de cadera

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    Más del 50% de los casos de caderas inestables se pueden resolver mediante la reducción cerrada de la luxación. Un intento sistemático para entender la causa de la inestabilidad, normalmente suele conducir a un tratamiento eficaz del problema cuando hace falta cirugía. Los componentes constreñidos o de retención han mejorado las posibilidades de resolver los problemas difíciles de inestabilidad, pero los efectos negativos potenciales de estos componentes deben tenerse también en cuenta. Los implantes tripolares, cuyos resultados clínicos en la literatura son muy alentadores, ocupan un lugar de elección en el arsenal terapéutico de la inestabilidad protética

    Nanoparticulate PdZn as a Novel Catalyst for ZnO Nanowire Growth.

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    ZnO nanowires have been grown by chemical vapour deposition (CVD) using PdZn bimetallic nanoparticles to catalyse the process. Nanocatalyst particles with mean particle diameters of 2.6 ± 0.3 nm were shown to catalyse the growth process, displaying activities that compare well with those reported for sputtered systems. Since nanowire diameters are linked to catalyst morphology, the size-control we are able to exhibit during particle preparation represents an advantage over existing approaches in terms of controlling nanowire dimensions, which is necessary in order to utilize the nanowires for catalytic or electrical applications.(See supplementary material 1).RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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