Influence of configuration effects on multiple burst simulation testing

During the initial phase of a lightning strike attachment on an aircraft, fast current pulses (rise time approximately 100 ns, I(sub max) approximately few kA) were measured, which can create equipment upsets or disturbances. This threat, made of repetitive pulses and usually called 'multiple bursts', can be reproduced at the equipment interfaces assuming that the transfer function of the structure was determined. The normalized waveform H (10 kA - 100 ns rise time) is the reference for one of these pulses. The importance of the coaxial return path termination for the injection of the wave H is emphasized. According to the constitutive materials of the test bed, and the adaptation of the line, the natural oscillations of the structure and the internal coupling mechanisms can be modified. As a conclusion, various test configurations in relation with the nature of the test bed and the characteristics of the generator are detailed, for a more accurate ground simulation of the attachment phase

All-integrated universal RF photonic spectral shaper

We demonstrate a microwave photonic spectral shaper in a silicon chip enabling distinct phase and amplitude modulation transformation. We show unprecedented RF filtering through monolithic integration of the spectral shaper with tunable ring resonators

Percolative shunting on electrified surface

The surface discharge of electrified dielectrics at high humidity is considered. The percolative nature of charge transport in electrets is established. Particular attention is given to the phenomena of adsorption and nucleation of electrically conducting phase in the cause of percolation cluster growth on electrified surface. The critical index of the correlation lenght for percolation cluster is found, and its value is in good agreement with the known theoretical estimations.Comment: 4 pages with 1 figure, revtex, published in Tech. Phys. Lett. 25 (1999) 877-879 with one additional figur

Green Roofs in Arid Cities. Efficiency as Energy Saving Strategy in Summer and Winter

Los techos vegetados constituyen estrategias de enverdecimiento que a escala edilicia controlan las altas temperaturas estivales en espacios interiores y a escala urbana contribuyen a mitigar el fenómeno isla de calor. Este trabajo evalúa, el efecto de cubiertas vegetadas con especies adaptadas -Aptenia cordifolia, Sedum spectabile- a climas cálido-secos sobre el comportamiento térmico de espacios interiores y su consecuente ahorro energético. Metodológicamente se ha monitoreado el desempeño térmico durante verano e invierno en tres box experimentales -uno con cubierta tradicional y dos vegetados-. Los resultados indican que las cubiertas vegetadas en verano disminuyen la temperatura interior 1,6 °C generando ahorros medios de energía para refrigeración del 30-35 %. En invierno si bien no hay variaciones notables, se observan ahorros energéticos diurnos del 2-4 %. El diseño de esta tecnología requiere evaluarse a nivel local para maximizar su eficiencia energética y garantizar la sustentabilidad urbano-edilicio según los recursos y tecnologías disponibles.Green roofs are greening strategies that controls the high summer temperatures in the indoor spaces at building scale and help mitigate the heat island phenomenon in urban scale. This work evaluates the effect of vegetated roofs with adapted species -Aptenia cordifolia, Sedum spectabile- in warm-dry climate in relation to the thermal behavior of indoors spaces and the consequent energy savings. Methodologically the thermal performance during summer and winter has monitored, in three experimental boxes- one with a traditional roof and two with vegetated roofs-. The results indicate that in the green roofs, indoor summer temperature decreases of 1,6 °C generate energy savings for refrigeration of 30 to 35%. In winter, although there are not notable variations, diurnal energy savings of 2-4% is observed. The design of these new technologies should be assessed at local level to maximize energy efficiency and ensure urban-building sustainability according to resources and technologies available.Eje: Eficiencia energética edilicia (Actas).Facultad de Arquitectura y Urbanism

Inhibition of Atrogin-1/MAFbx Mediated MyoD Proteolysis Prevents Skeletal Muscle Atrophy In Vivo

Ubiquitin ligase Atrogin1/Muscle Atrophy F-box (MAFbx) up-regulation is required for skeletal muscle atrophy but substrates and function during the atrophic process are poorly known. The transcription factor MyoD controls myogenic stem cell function and differentiation, and seems necessary to maintain the differentiated phenotype of adult fast skeletal muscle fibres. We previously showed that MAFbx mediates MyoD proteolysis in vitro. Here we present evidence that MAFbx targets MyoD for degradation in several models of skeletal muscle atrophy. In cultured myotubes undergoing atrophy, MAFbx expression increases, leading to a cytoplasmic-nuclear shuttling of MAFbx and a selective suppression of MyoD. Conversely, transfection of myotubes with sh-RNA-mediated MAFbx gene silencing (shRNAi) inhibited MyoD proteolysis linked to atrophy. Furthermore, overexpression of a mutant MyoDK133R lacking MAFbx-mediated ubiquitination prevents atrophy of mouse primary myotubes and skeletal muscle fibres in vivo. Regarding the complex role of MyoD in adult skeletal muscle plasticity and homeostasis, its rapid suppression by MAFbx seems to be a major event leading to skeletal muscle wasting. Our results point out MyoD as the second MAFbx skeletal muscle target by which powerful therapies could be developed

The Tumor Suppressive Role of eIF3f and Its Function in Translation Inhibition and rRNA Degradation

Deregulated translation plays an important role in human cancer. We previously reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in pancreatic cancer. Whether decreased eIF3f expression can transform normal epithelial cells is not known. In our current study, we found evidence that stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells increased cell size, nuclear pleomorphism, cytokinesis defects, cell proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3-dimensional irregular masses. Our findings support the tumor suppressive role of eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both cap-dependent and cap-independent translation. An increase in the ribosomal RNA (rRNA) level was suggested to promote the generation of cancer. The regulatory mechanism of rRNA degradation in mammals is not well understood. We demonstrated here that eIF3f promotes rRNA degradation through direct interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is required for maintaining rRNA stability: under stress conditions, eIF3f dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from degradation. We also demonstrated that rRNA degradation occurred in non-P body, non-stress granule cytoplasmic foci that contain eIF3f. Our findings established a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest that the tumor suppressive function of eIF3f may link to impaired rRNA degradation and translation

The mode and tempo of hepatitis C virus evolution within and among hosts

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a rapidly-evolving RNA virus that establishes chronic infections in humans. Despite the virus' public health importance and a wealth of sequence data, basic aspects of HCV molecular evolution remain poorly understood. Here we investigate three sets of whole HCV genomes in order to directly compare the evolution of whole HCV genomes at different biological levels: within- and among-hosts. We use a powerful Bayesian inference framework that incorporates both among-lineage rate heterogeneity and phylogenetic uncertainty into estimates of evolutionary parameters.</p> <p>Results</p> <p>Most of the HCV genome evolves at ~0.001 substitutions/site/year, a rate typical of RNA viruses. The antigenically-important <it>E1/E2 </it>genome region evolves particularly quickly, with correspondingly high rates of positive selection, as inferred using two related measures. Crucially, in this region an exceptionally higher rate was observed for within-host evolution compared to among-host evolution. Conversely, higher rates of evolution were seen among-hosts for functionally relevant parts of the <it>NS5A </it>gene. There was also evidence for slightly higher evolutionary rate for HCV subtype 1a compared to subtype 1b.</p> <p>Conclusions</p> <p>Using new statistical methods and comparable whole genome datasets we have quantified, for the first time, the variation in HCV evolutionary dynamics at different scales of organisation. This confirms that differences in molecular evolution between biological scales are not restricted to HIV and may represent a common feature of chronic RNA viral infection. We conclude that the elevated rate observed in the <it>E1/E2 </it>region during within-host evolution more likely results from the reversion of host-specific adaptations (resulting in slower long-term among-host evolution) than from the preferential transmission of slowly-evolving lineages.</p

THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria

Phenotypic screens for bactericidal compounds against drug-resistant tuberculosis are beginning to yield novel inhibitors. However, reliable target identification remains challenging. Here, we show that tetrahydropyrazo[1,5-a]pyrimidine-3-carboxamide (THPP) selectively pulls down EchA6 in a stereospecific manner, instead of the previously assigned target Mycobacterium tuberculosis MmpL3. While homologous to mammalian enoyl-coenzyme A (CoA) hydratases, EchA6 is non-catalytic yet essential and binds long-chain acyl-CoAs. THPP inhibitors compete with CoA-binding, suppress mycolic acid synthesis, and are bactericidal in a mouse model of chronic tuberculosis infection. A point mutation, W133A, abrogated THPP-binding and increased both the in vitro minimum inhibitory concentration and the in vivo effective dose 99 in mice. Surprisingly, EchA6 interacts with selected enzymes of fatty acid synthase II (FAS-II) in bacterial two-hybrid assays, suggesting essentiality may be linked to feeding long-chain fatty acids to FAS-II. Finally, our data show that spontaneous resistance-conferring mutations can potentially obscure the actual target or alternative targets of small molecule inhibitors

Phylodynamics of Hepatitis C Virus Subtype 2c in the Province of Córdoba, Argentina

The Hepatitis C Virus Genotype 2 subtype 2c (HCV-2c) is detected as a low prevalence subtype in many countries, except in Southern Europe and Western Africa. The current epidemiology of HCV in Argentina, a low-prevalence country, shows the expected low prevalence for this subtype. However, this subtype is the most prevalent in the central province of Córdoba. Cruz del Eje (CdE), a small rural city of this province, shows a prevalence for HCV infections of 5%, being 90% of the samples classified as HCV-2c. In other locations of Córdoba Province (OLC) with lower prevalence for HCV, HCV-2c was recorded in about 50% of the samples. The phylogenetic analysis of samples from Córdoba Province consistently conformed a monophyletic group with HCV-2c sequences from all the countries where HCV-2c has been sequenced. The phylogeographic analysis showed an overall association between geographical traits and phylogeny, being these associations significant (α = 0.05) for Italy, France, Argentina (places other than Córdoba), Martinique, CdE and OLC. The coalescence analysis for samples from CdE, OLC and France yielded a Time for the Most Common Recent Ancestor of about 140 years, whereas its demographic reconstruction showed a “lag” phase in the viral population until 1880 and then an exponential growth until 1940. These results were also obtained when each geographical area was analyzed separately, suggesting that HCV-2c came into Córdoba province during the migration process, mainly from Europe, which is compatible with the history of Argentina of the early 20th century. This also suggests that the spread of HCV-2c occurred in Europe and South America almost simultaneously, possibly as a result of the advances in medicine technology of the first half of the 20th century