Non-local interactions in hydrodynamic turbulence at high Reynolds numbers: the slow emergence of scaling laws

We analyze the data stemming from a forced incompressible hydrodynamic simulation on a grid of 2048^3 regularly spaced points, with a Taylor Reynolds number of Re~1300. The forcing is given by the Taylor-Green flow, which shares similarities with the flow in several laboratory experiments, and the computation is run for ten turnover times in the turbulent steady state. At this Reynolds number the anisotropic large scale flow pattern, the inertial range, the bottleneck, and the dissipative range are clearly visible, thus providing a good test case for the study of turbulence as it appears in nature. Triadic interactions, the locality of energy fluxes, and structure functions of the velocity increments are computed. A comparison with runs at lower Reynolds numbers is performed, and shows the emergence of scaling laws for the relative amplitude of local and non-local interactions in spectral space. The scalings of the Kolmogorov constant, and of skewness and flatness of velocity increments, performed as well and are consistent with previous experimental results. Furthermore, the accumulation of energy in the small-scales associated with the bottleneck seems to occur on a span of wavenumbers that is independent of the Reynolds number, possibly ruling out an inertial range explanation for it. Finally, intermittency exponents seem to depart from standard models at high Re, leaving the interpretation of intermittency an open problem.Comment: 8 pages, 8 figure

Congenital Chagas Disease: Recommendations for Diagnosis, Treatment and Control of Newborns, Siblings and Pregnant Women

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Setting up a Common European Asylum System : Report on the application of existing instruments and proposals for the new system

The study assesses firstly the evaluation process of the first generation of asylum instruments while underlining the possibilities to improve it. It analyses secondly the asylum "acquis" regarding distribution of refugees between Member States, the eligibility for protection, the status of protected persons regarding detention and vulnerability, asylum procedures and the external dimension by formulating short-term recommendations of each area. Its last part is devoted to the long term evolution of the Common European Asylum System regarding the legal context including the accession of the EU to the Geneva Convention, the institutional perspectives including the new European Support Office, the jurisdictional perspective, the substantive perspective, the distributive perspective and the external perspective

Modeling oscillatory Microtubule--Polymerization

Polymerization of microtubules is ubiquitous in biological cells and under certain conditions it becomes oscillatory in time. Here simple reaction models are analyzed that capture such oscillations as well as the length distribution of microtubules. We assume reaction conditions that are stationary over many oscillation periods, and it is a Hopf bifurcation that leads to a persistent oscillatory microtubule polymerization in these models. Analytical expressions are derived for the threshold of the bifurcation and the oscillation frequency in terms of reaction rates as well as typical trends of their parameter dependence are presented. Both, a catastrophe rate that depends on the density of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay reaction, such as the depolymerization of shrinking microtubules or the decay of oligomers, support oscillations. For a tubulin dimer concentration below the threshold oscillatory microtubule polymerization occurs transiently on the route to a stationary state, as shown by numerical solutions of the model equations. Close to threshold a so--called amplitude equation is derived and it is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure

Upper limb disease evolution in exon 53 skipping eligible patients with Duchenne muscular dystrophy

Objective: To understand the natural disease upper limb progression over 3 years of ambulatory and non-ambulatory patients with Duchenne muscular dystrophy (DMD) using functional assessments and quantitative magnetic resonance imaging (MRI) and to exploratively identify prognostic factors. Methods: Forty boys with DMD (22 non-ambulatory and 18 ambulatory) with deletions in dystrophin that make them eligible for exon 53-skipping therapy were included. Clinical assessments, including Brooke score, motor function measure (MFM), hand grip and key pinch strength, and upper limb distal coordination and endurance (MoviPlate), were performed every 6 months and quantitative MRI of fat fraction (FF) and lean muscle cross sectional area (flexor and extensor muscles) were performed yearly. Results: In the whole population, there were strong nonlinear correlations between outcome measures. In non-ambulatory patients, annual changes over the course of 3 years were detected with high sensitivity standard response mean (|SRM| ≥0.8) for quantitative MRI-based FF, hand grip and key pinch, and MFM. Boys who presented with a FF27% were able to bring a glass to their mouth and retained this ability in the following 3 years. Ambulatory patients with grip strength >35% of predicted value and FF <10% retained ambulation 3 years later. Interpretation: We demonstrate that continuous decline in upper limb strength, function, and MRI measured muscle structure can be reliably measured in ambulatory and non-ambulatory boys with DMD with high SRM and strong correlations between outcomes. Our results suggest that a combination of grip strength and FF can be used to predict important motor milestones

Maternal Infection with Trypanosoma cruzi and Congenital Chagas Disease Induce a Trend to a Type 1 Polarization of Infant Immune Responses to Vaccines

Vaccines are of crucial importance to prevent morbidity and mortality due to infectious diseases in childhood. A modulation of the fetal/neonatal immune system (considered immature) toward Th1 or Th2 dominance could modify responses to vaccines administered in early life. T. cruzi is the agent of Chagas' disease, in Latin America currently infecting about 2 million women at fertile ages who are susceptible to transmitting the parasite to their fetus. In previous studies we showed that T. cruzi-infected mothers can induce a pro-inflammatory environment in their uninfected neonates (M+B−), whereas congenitally infected newborns (M+B+) are able to develop a pro-Th1 parasite-specific T cell response. In the present study, we analysed the cellular and/or antibody responses to Bacillus Calmette Guerin (BCG), hepatitis B birus (HBV), diphtheria and tetanus vaccines in 6- to 7-month-old infants living in Bolivia. M+B− infants produced more IFN-γ in response to BCG, whereas M+B+ infants developed a stronger IFN-γ response to hepatitis B, diphtheria and tetanus vaccines and enhanced antibody production to HBs antigen. These results show that both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period and that T. cruzi infection in early life tends to favour type 1 immune responses to vaccinal antigens

NMR resonance assignments of NarE, a putative ADP-ribosylating toxin from Neisseria meningitidis

NarE is a 16 kDa protein identified from Neisseria meningitidis, one of the bacterial pathogens responsible for meningitis. NarE belongs to the ADP-ribosyltransferase family and catalyses the transfer of ADP-ribose moieties to arginine residues in target protein acceptors. Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and alter essential functions of eukaryotic cells. NarE was proposed to bind iron through a Fe–S center which is supposed to be implied in catalysis. We have produced and purified uniformly labeled 15N- and 15N/13C-NarE and assigned backbone and side-chain resonances using multidimensional heteronuclear NMR spectroscopy. These assignments provide the starting point for the three-dimensional structure determination of NarE and the characterization of the role of the Fe–S center in the catalytic mechanism

Individual Actin Filaments in a Microfluidic Flow Reveal the Mechanism of ATP Hydrolysis and Give Insight Into the Properties of Profilin

A novel microfluidic approach allows the analysis of the dynamics of individual actin filaments, revealing both their local ADP/ADP-Pi-actin composition and that Pi release is a random mechanism

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease