LDEF solar cell radiation effects analysis

Because of the extended time that the Long Duration Exposure Facility (LDEF) mission stayed in space, the solar cells on the satellite experienced greater environments than originally planned. The cells showed an overall degradation in performance that is due to the combined effects of the various space environments. The purpose of this analysis is to calculate the effect of the accumulated radiation on the solar cells, thereby helping Marshall Space Flight Center (MSFC) to unravel the relative power degradation from the different environments

Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Druglike Inhibitor

Calculation of the absolute free energy of binding (ΔGbind) for a complex in solution is challenging owing to the need for adequate configurational sampling and an accurate energetic description, typically with a force field (FF). In this study, Monte Carlo (MC) simulations with improved side-chain and backbone sampling are used to assess ΔGbind for the complex of a druglike inhibitor (MIF180) with the protein macrophage migration inhibitory factor (MIF) using free energy perturbation (FEP) calculations. For comparison, molecular dynamics (MD) simulations were employed as an alternative sampling method for the same system. With the OPLS-AA/M FF and CM5 atomic charges for the inhibitor, the ΔGbind results from the MC/FEP and MD/FEP simulations, −8.80 ± 0.74 and −8.46 ± 0.85 kcal/mol, agree well with each other and with the experimental value of −8.98 ± 0.28 kcal/mol. The convergence of the results and analysis of the trajectories indicate that sufficient sampling was achieved for both approaches. Repeating the MD/FEP calculations using current versions of the CHARMM and AMBER FFs led to a 6 kcal/mol range of computed ΔGbind. These results show that calculation of accurate ΔGbind for large ligands is both feasible and numerically equivalent, within error limits, using either methodology

Prediction of the Water Content in Protein Binding Sites

An efficient molecular simulation methodology has been developed to determine the positioning of water molecules in the binding site of a protein or protein-ligand complex. Occupancies and absolute binding free energies of water molecules are computed using a statistical thermodynamics approach. The methodology, referred to as JAWS, features “θ-water” molecules that can appear and disappear on a binding-site grid. Key approximations render the technique far more efficient than conventional free energy simulations. Testing of JAWS on five diverse examples (neuraminidase, scytalone dehydratase, major urinary protein 1, β-lactoglobulin, and COX-2) demonstrates its accuracy in locating hydration sites in comparison to results from high-resolution crystal structures. Possible applications include aid in refinement of protein crystal structures, drug lead optimization, setup of docking calculations and simulations of protein-ligand complexes

Derivation of genetic interaction networks from quantitative phenotype data

We have generalized the derivation of genetic-interaction networks from quantitative phenotype data. Familiar and unfamiliar modes of genetic interaction were identified and defined. A network was derived from agar-invasion phenotypes of mutant yeast. Mutations showed specific modes of genetic interaction with specific biological processes. Mutations formed cliques of significant mutual information in their large-scale patterns of genetic interaction. These local and global interaction patterns reflect the effects of gene perturbations on biological processes and pathways

Rank-(n – 1) convexity and quasiconvexity for divergence free fields

The CAST experiment at CERN (European Organization of Nuclear Research) searches for axions from the sun. The axion is a pseudoscalar particle that was motivated by theory thirty years ago, with the intention to solve the strong CP problem. Together with the neutralino, the axion is one of the most promising dark matter candidates. The CAST experiment has been taking data during the last two years, setting an upper limit on the coupling of axions to photons more restrictive than from any other solar axion search in the mass range below 0.1 eV. In 2005 CAST will enter a new experimental phase extending the sensitivity of the experiment to higher axion masses. The CAST experiment strongly profits from technology developed for high energy physics and for X-ray astronomy: A superconducting prototype LHC magnet is used to convert potential axions to detectable X-rays in the 1-10 keV range via the inverse Primakoff effect. The most sensitive detector system of CAST is a spin-off from space technology, a Wolter I type X-ray optics in combination with a prototype pn-CCD developed for ESA's XMM-Newton mission. As in other rare event searches, background suppression and a thorough shielding concept is essential to improve the sensitivity of the experiment to the best possible. In this context CAST offers the opportunity to study the background of pn-CCDs and its long term behavior in a terrestrial environment with possible implications for future space applications. We will present a systematic study of the detector background of the pn-CCD of CAST based on the data acquired since 2002 including preliminary results of our background simulations.Comment: 11 pages, 8 figures, to appear in Proc. SPIE 5898, UV, X-Ray, and Gamma-Ray Space Instrumentation for Astronomy XI

Unusual presentation of thyrotoxicosis as complete heart block and renal failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Thyrotoxicosis is a clinical entity often very difficult to diagnose without biochemical confirmation as its clinical features can be highly varied. The most common cardiac manifestations of thyrotoxicosis are resting sinus tachycardia, supraventricular tachycardia including atrial fibrillation and atrial flutter with or without cardiac failure. Bradycardia and atrio-ventricular conduction defects are very uncommon in thyrotoxicosis.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old Caucasian man presenting with progressive weight loss, abnormal liver function, acute renal failure and complete heart block due to thyrotoxicosis.</p> <p>Conclusion</p> <p>Thyrotoxicosis should be considered as a possible diagnosis in patients with bradycardia and heart blocks associated with abnormal symptoms like weight loss. Nevertheless, the clinical, electrophysiological and biochemical abnormalities associated with thyrotoxicosis may be completely reversible restoring euthyroid state.</p

Un anteproyecto de 1961 para la instalación de calefacción urbana en Pamplona

En octubre de 2003, en el archivo del Departamento de Edificación de la Escuela de Arquitectura de la Universidad de Navarra, se encuentra una recopilación de planos y documentos escritos que llevan por título “Anteproyecto de Calefacción Urbana en Pamplona”, firmada por el ingeniero industrial Joaquín Castiella en junio de 1961. Esta documentación la traslada al Departamento cuando es profesor de la Escuela de Arquitectura. Rescatado del olvido de los archivos, este anteproyecto resulta un descubrimiento que se pone al alcance de los interesados en urbanismo e infraestructuras energéticas urbanas. Este artículo pretende transmitir el contenido del proyecto de Joaquín Castiella ubicándolo en un contexto técnico e histórico que permita su comprensión

Fertility preservation in boys : recent developments and new insights

BACKGROUND: Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility. OBJECTIVE AND RATIONALE: With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss. SEARCH METHODS: Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity. OUTCOMES: Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic. Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation. LIMITATIONS, REASONS FOR CAUTION: The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention. WIDER IMPLICATIONS: The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss.Peer reviewe