Preliminary Studies of Magnetic NDE Techniques for Identifying Neutron Embrittlement of Pressure Vessel Steel

In operating nuclear reactors, the steel pressure vessel is exposed to neutron irradiation. The high energy part (\u3e1 MeV) of this irradiation, over a long period, makes the steel brittle and susceptible to rupture

Trace element carrier phases in primitive chondrite matrix: Implications for volatile element fractionation in the inner Solar System

Published versio

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Fishing for Prion Protein Function

The prion protein is infamous for its role in devastating neurological diseases, but its normal, physiological function has remained mysterious. A new study uses the experimentally tractable zebrafish model to obtain fresh clues to this puzzle

Seguimiento de trayectorias tridimensionales de un quadrotor mediante control PVA

Este trabajo presenta el modelado de un quadrotor como un sistema multicuerpo llevado a cabo mediante el software Vehicle- Sim, en el que los diferentes componentes del sistema son descritos mediante una estructura paterno-filial señalando las restricciones físicas entre ellos. Los modelos estructural y aerodinámico han sido desarrollados mediante este software, ampliamente utilizado en la simulación del comportamiento dinámico de vehículos. Sobre el modelo resultante se he desarrollado un algoritmo de control basado en la metodologia PVA con la finalidad de obtener un seguimiento de trayectoria mediante acciones de control suaves. Empleando la metodología convencional de control PVA no es posible estabilizar el vehículo en todos los rangos de posicionamiento lateral (y) y longitudinal (x). En este artículo los autores muestran como esta limitación en el diseño de una estrategia de control PVA convencional es solventada con una modificación consistente en sustituir los parámetros constantes del PVA clásico por funciones dependientes del desplazamiento. El sistema de control es implementado para adecuarse a los requerimientos de las actuaciones y se diseña sobre la plataforma de simulación multidominio Simulink. Con la finalidad de obtener una importante mejora en la respuesta de posicionamiento, se im- plementa un generador de trayectorias continuas. Una vez que el modelo es desarrollado y el sistema de control implementado, los autores presentan el modelo matemático y los resultados de las simulaciones realizadas. Éstas validan el empleo tanto de la metodología de control PVA aplicada, como de la alimentación de trayectorias predefinidas, no sólo para la posición, sino también para la velocidad y aceleración

Genetic Engineering in Streptomyces roseosporus to Produce Hybrid Lipopeptide Antibiotics

SummaryDaptomycin is a lipopeptide antibiotic produced by a nonribosomal peptide synthetase (NRPS) in Streptomyces roseosporus. The holoenzyme is composed of three subunits, encoded by the dptA, dptBC, and dptD genes, each responsible for incorporating particular amino acids into the peptide. We introduced expression plasmids carrying dptD or NRPS genes encoding subunits from two related lipopeptide biosynthetic pathways into a daptomycin nonproducing strain of S. roseosporus harboring a deletion of dptD. All constructs successfully complemented the deletion in trans, generating three peptide cores related to daptomycin. When these were coupled with incomplete methylation of 1 amino acid and natural variation in the lipid side chain, 18 lipopeptides were generated. Substantial amounts of nine of these compounds were readily obtained by fermentation, and all displayed antibacterial activity against gram-positive pathogens

Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis

<p>Abstract</p> <p>Background</p> <p>Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population.</p> <p>Methods</p> <p>In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint.</p> <p>Results</p> <p>Of 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available.</p> <p>Conclusion</p> <p>In this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00556296">NCT00556296</a></p

Decay constants, light quark masses and quark mass bounds from light quark pseudoscalar sum rules

The flavor $ud$ and $us$ pseudoscalar correlators are investigated using families of finite energy sum rules (FESR's) known to be very accurately satisfied in the isovector vector channel. It is shown that the combination of constraints provided by the full set of these sum rules is sufficiently strong to allow determination of both the light quark mass combinations $m_u+m_d$, $m_s+m_u$ and the decay constants of the first excited pseudoscalar mesons in these channels. The resulting masses and decay constants are also shown to produce well-satisfied Borel transformed sum rules, thus providing non-trivial constraints on the treatment of direct instanton effects in the FESR analysis. The values of $m_u+m_d$ and $m_s+m_u$ obtained are in good agreement with the values implied by recent hadronic $\tau$ decay analyses and the ratios obtained from ChPT. New light quark mass bounds based on FESR's involving weight functions which strongly suppress spectral contributions from the excited resonance region are also presented.Comment: 28 pages, 10 figure

Thermal Dileptons from pi - rho Interactions in a Hot Pion Gas

A systematic study of low mass dilepton production from $\pi-\rho$ interactions in a hot medium is presented. Applying finite temperature perturbation theory the dilepton rate, respectively the virtual photon rate, is computed up to order $g_\rho^2$. For dilepton masses below the $\rho$ the two-body reactions $\pi\pi\to \rho \gamma^*$, $\pi\rho\to \pi \gamma^*$, and the decay process $\rho \to \pi \pi \gamma^*$ give significant contributions. Non-equilibrium contributions to the thermal rate are estimated, including the modification of the particle distribution function with non-zero pion chemical potential. The comparison of the dilepton rate with the recent data measured in nucleus-nucleus collisions at SPS energy by the CERES Collaboration is also performed. It is shown that the additional thermal dileptons from $\pi-\rho$ interactions can partially account for the access of the soft dilepton yield seen experimentally.Comment: 21 pages LaTeX, 8 figs with epsfig.sty macro include