Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design

The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to generate inhibitor libraries for these enzymes, and together with computational methodologies have been demonstrated capable for the selection of lead compounds. The high structural flexibility of plasmepsins, revealed by their X-ray structures and molecular dynamics simulations, made even more complicated the prediction of putative binding modes, and therefore, the use of common computational tools, like docking and free-energy calculations. In this review, we revised the computational strategies utilized so far, for the structure-function relationship studies concerning the plasmepsin family, with special focus on the recent advances in the improvement of the linear interaction estimation (LIE) method, which is one of the most successful methodologies in the evaluation of plasmepsin-inhibitor binding affinity

Las razas bovinas carniceras en Argentina : carne for export

Fil: Fornieles, Alejandro S. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Producción Bovinos para Carne; Argentina.Fil: Cervini, María L. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Producción Bovinos para Carne; Argentina.Fil: Gil, Susana B. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Producción Bovinos para Carne; Argentina.Fil: Demarco, Diego. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Producción Bovinos para Carne; Argentina.Fil: De la Orden, Jorge L. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Producción Bovinos para Carne; Argentina.En un principio había razas bovinas que respondían a biotipos carniceros o lecheros. Hoy, a los\nefectos productivos, se habla de biotipos continentales, británicos o índicos. Las razas son las\nvariables genéticas que se manejan dentro del sistema. No tienen ninguna característica especial que\nlas hagan mejores o peores, sino que según sea el sistema de producción será la raza que convenga\nutilizar

Statistical modelling and satellite monitoring of upward light from public lighting

In this work, we propose an approach to estimating the amount of light wasted by being sent towards the upper hemisphere from urban areas. This is a source of light pollution. The approach is based on a predictive model that provides the fraction of light directed skywards in terms of a small set of identified explanatory variables that characterise the urban landscape and its light sources. The model, built via the statistical analysis of a wide sample of basic urban scenarios to compute accurately the amount of light wasted at each of them, establishes an optimal linear regression function that relates the fraction of wasted flux to relevant variables like the kind of luminaires, the street fill factor, the street width, the building and luminaire heights and the walls and pavement reflectances. We applied this model to evaluate the changes in emissions produced at two urban nuclei in the Deltebre municipality of Catalonia. The results agree reasonably well with those deduced from the radiance measurements made with the VIIRS instrument onboard the Suomi-NPP Earth orbiting satellite

Etnografía : una visión desde la orientación analítica

RESUMEN: La etnografía es uno de los métodos de la investigación social que ha evolucionado tanto en las últimas décadas que ha pasado de una herramienta de poder, de obtención de información, de sustantivación de un quehacer, a un verbo, un proceso, determinado por la actitud del indagador. La etnografía ha dejado su estatus de técnica para pasar al orden del método, siendo las técnicas actualizaciones de éste, tales como la entrevista, los grupos de discusión, entre otros (Ramírez, 1999)

Analysis of a superbolide from a Damocloid observed over Spain on July 13, 2012

A superbolide with an estimated absolute magnitude of-20±1was seen on 2012 July 13 over the centre and south of Spain. This extraordinary event, which was witnessed by numerous casual observers, was recorded in the framework of the continuous fireball monitoring and meteor spectroscopy campaign performed by the SPanish Meteor Network (SPMN). Thus, because of optimal weather conditions, the bolide was imaged from 10 meteor observing stations. Here we present the analysis of this magnificent event, which is the brightest fireball ever recorded by our team. The atmospheric trajectory of the bolide and the orbit in the Solar system of the parent meteoroid were obtained. The emission spectrum produced during the ablation of this particle is also discussed.We found that the meteoroid, which was following a Halley Type Comet orbit, was depleted in Na and had a tensile strength one order of magnitude higher than that corresponding to typical cometary materials. By means of orbital analysis tools we have investigated the likely parent body of this particle and the results suggest that the progenitor is a damocloid. The impact area of the hypothetical remnants of the meteoroid is also given and a search for meteorites was performed, but none was found.Ministerio de Ciencia e Innovación AYA2009-13227 AYA2009-06330-E AYA2011-26522Junta de Andalucía P09-FQM-455

Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

We have carried out a series of extended unbiased molecular dynamics (MD) simulations (up to 10 \u3bcs long, 3c162 \u3bcs in total) complemented by replica-exchange with the collective variable tempering (RECT) approach for several human telomeric DNA G-quadruplex (GQ) topologies with TTA propeller loops. We used different AMBER DNA force-field variants and also processed simulations by Markov State Model (MSM) analysis. The slow conformational transitions in the propeller loops took place on a scale of a few \u3bcs, emphasizing the need for long simulations in studies of GQ dynamics. The propeller loops sampled similar ensembles for all GQ topologies and for all force-field dihedral-potential variants. The outcomes of standard and RECT simulations were consistent and captured similar spectrum of loop conformations. However, the most common crystallographic loop conformation was very unstable with all force-field versions. Although the loss of canonical \u3b3-trans state of the first propeller loop nucleotide could be related to the indispensable bsc0 \u3b1/\u3b3 dihedral potential, even supporting this particular dihedral by a bias was insufficient to populate the experimentally dominant loop conformation. In conclusion, while our simulations were capable of providing a reasonable albeit not converged sampling of the TTA propeller loop conformational space, the force-field description still remained far from satisfactory

A Study of the Near-Ultraviolet Spectrum of Vega

UV, optical, and near-IR spectra of Vega have been combined to test our understanding of stellar atmospheric opacities, and to examine the possibility of constraining chemical abundances from low-resolution UV fluxes. We have carried out a detailed analysis assuming Local Thermodynamic Equilibrium (LTE) to identify the most important contributors to the UV continuous opacity: H, H$^{-}$, C I, and Si II. Our analysis also assumes that Vega is spherically symmetric and its atmosphere is well described with the plane parallel approximation. Comparing observations and computed fluxes we have been able to discriminate between two different flux scales that have been proposed, the IUE-INES and the HST scales, favoring the latter. The effective temperature and angular diameter derived from the analysis of observed optical and near-UV spectra are in very good agreement with previous determinations based on different techniques. The silicon abundance is poorly constrained by the UV observations of the continuum and strong lines, but the situation is more favorable for carbon and the abundances inferred from the UV continuum and optical absorption lines are in good agreement. Some spectral intervals in the UV spectrum of Vega that the calculations do not reproduce well are likely affected by deviations from LTE, but we conclude that our understanding of UV atmospheric opacities is fairly complete for early A-type stars.Comment: 13 pages, 9 figures, to be published in Ap

Intramuscular EMG-driven Musculoskeletal Modelling: Towards Implanted Muscle Interfacing in Spinal Cord Injury Patients

Objective: Surface EMG-driven modelling has been proposed as a means to control assistive devices by estimating joint torques. Implanted EMG sensors have several advantages over wearable sensors but provide a more localized information on muscle activity, which may impact torque estimates. Here, we tested and compared the use of surface and intramuscular EMG measurements for the estimation of required assistive joint torques using EMG driven modelling. Methods: Four healthy subjects and three incomplete spinal cord injury (SCI) patients performed walking trials at varying speeds. Motion capture marker trajectories, surface and intramuscular EMG, and ground reaction forces were measured concurrently. Subject-specific musculoskeletal models were developed for all subjects, and inverse dynamics analysis was performed for all individual trials. EMG-driven modelling based joint torque estimates were obtained from surface and intramuscular EMG. Results: The correlation between the experimental and predicted joint torques was similar when using intramuscular or surface EMG as input to the EMG-driven modelling estimator in both healthy individuals and patients. Conclusion: We have provided the first comparison of non-invasive and implanted EMG sensors as input signals for torque estimates in healthy individuals and SCI patients. Significance: Implanted EMG sensors have the potential to be used as a reliable input for assistive exoskeleton joint torque actuation

Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states

Over two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study, we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 C