Lagrangian Coherent Structures in three-dimensional flows

arXiv:1207.1975v1Lagrangian Coherent Structures (LCS) act as the organizers of transport in fluid flows and are crucial to understand their stirring and mixing properties. In the case of oceanic flows, LCS are known to drive biological dynamics, from plankton to top predators, which stresses the importance of their characterization in realistic flows. Lyapunov exponents are useful tools to compute LCSs. In this paper we have used the Finite-Size Lyapunov Exponent (FSLE) to identify LCSs in two different types of three-dimensional turbulent velocity fields. First, in a canonical turbulent flow (channel flow between two parallel plates) the LCSs have a complex three-dimensional shape and are advected by the flow. Second, in an oceanographic setting (a regional simulation of the Benguela area) the LCSs also show a complex pattern on the horizontal but the small vertical velocities typical of oceanic flows result in a curtain-like shape.Supported by Ministerio de Econom a y Competitividad (Spain) and Fondo Europeo de Desarrollo Regional through projects FISICOS (FIS2007-60327). JHB acknowledges nancial support of the Portuguese FCT (Foundation for Science and Technology) and Fundo Social Europeu (FSE/QREN/POPH) through the predoctoral grant SFRH/BD/63840/2009.Peer reviewe

Characterization of coherent structures in three-dimensional turbulent flows using the finite-size Lyapunov exponent

arXiv:1207.1975In this paper, we use the finite-size Lyapunov exponent (FSLE) to characterize Lagrangian coherent structures in three-dimensional (3D) turbulent flows. Lagrangian coherent structures act as the organizers of transport in fluid flows and are crucial to understand their stirring and mixing properties. Generalized maxima (ridges) of the FSLE fields are used to locate these coherent structures. 3D FSLE fields are calculated in two phenomenologically distinct turbulent flows: a wall-bounded flow (channel flow) and a regional oceanic flow obtained by the numerical solution of the primitive equations where two-dimensional (2D) turbulence dominates. In the channel flow, autocorrelations of the FSLE field show that the structure is substantially different from the near wall to the mid-channel region and relates well to the more widely studied Eulerian coherent structure of the turbulent channel flow. The ridges of the FSLE field have complex shapes due to the 3D character of the turbulent fluctuations. In the oceanic flow, strong horizontal stirring is present and the flow regime is similar to that of 2D turbulence where the domain is populated by coherent eddies that interact strongly. This in turn results in the presence of high FSLE lines throughout the domain leading to strong non-local mixing. The ridges of the FSLE field are quasi-vertical surfaces, indicating that the horizontal dynamics dominates the flow. Indeed, due to rotation and stratification, vertical motions in the ocean are much less intense than horizontal ones. This suppression is absent in the channel flow, as the 3D character of the FSLE ridges shows. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to 'Lyapunov analysis: from dynamical systems theory to applications'. © 2013 IOP Publishing Ltd.This work was supported by Ministerio de Economía y Competitividad (Spain) and Fondo Europeo de Desarrollo Regional through project FISICOS (FIS2007-60327). JHB acknowledges financial support of the Portuguese FCT (Foundation for Science and Technology) and Fundo Social Europeo (FSE/QREN/POPH) through the predoctoral grant SFRH/BD/63840/2009.N

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases

Oceanic three-dimensional Lagrangian Coherent Structures: A study of a mesoscale eddy in the Benguela ocean region

We study three dimensional oceanic Lagrangian Coherent Structures (LCSs) in the Benguela region, as obtained from an output of the ROMS model. To do that we first compute Finite-Size Lyapunov exponent (FSLE) fields in the region volume, characterizing mesoscale stirring and mixing. Average FSLE values show a general decreasing trend with depth, but there is a local maximum at about 100 m depth. LCSs are extracted as ridges of the calculated FSLE fields. They present a "curtain-like" geometry in which the strongest attracting and repelling structures appear as quasivertical surfaces. LCSs around a particular cyclonic eddy, pinched off from the upwelling front are also calculated. The LCSs are confirmed to provide pathways and barriers to transport in and out of the eddy

Metal alloys, matrix inclusions and manufacturing techniques of Moinhos de Golas collection (North Portugal): a study by micro-EDXRF, SEM–EDS, optical microscopy and X-ray radiography

"Article:820"A collection of 35 metallic artefacts comprising various typologies, some of which can be attributed to the Bronze Age and others to later periods, were studied to provide detailed information on elemental composition, manufacturing techniques and preservation state. Elemental analysis by micro-EDXRF and SEM–EDS was performed to investigate the use of different alloys and to study the presence of microstructural heterogeneities, as inclusions. X-ray radiography, optical microscopy and SEM–EDS were used to investigate manufacturing techniques and degradation features. Results showed that most of the artefacts were produced in a binary bronze alloy (Cu–Sn) with 10–15 wt% Sn and a low concentration of impurities. Other artefacts were produced in copper or in brass, the latest with varying contents of Zn, Sn and Pb. A variety of inclusions in the metal matrices were also found, some related to specific types of alloys, as (Cu–Ni)S2 in coppers, or ZnS in brasses. Microstructural observations revealed that the majority of the artefacts were subjected to cycles of thermomechanical processing after casting, being evident that among some artefacts different parts were subjected to distinct treatments. The radiographic images revealed structural heterogeneities related to local corrosion processes and fissures that seem to have developed in wear-tension zones, as in the handle of some daggers. Radiographic images were also useful to detect the use of different materials in one particular brass artefact, revealing the presence of a possible Cu–Sn solder.This work was funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT— Fundação para a Ciência e a Tecnologia under the project UID/CTM/ 50025/2013 to CENIMAT/I3N. C2 TN/IST authors gratefully acknowledge the FCT support through the UID/Multi/04349/2013 project. EF acknowledges FCT for the grant SFRH/BPD/97360/2013. JF acknowledge FCT for the grant SFRH/BD/65143/2009. Part of this project has been done in the framework of the FCT project ENARDAS (PTDC/HISARQ/112983/2009).info:eu-repo/semantics/publishedVersio

Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial

Objectives SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). Background AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. Methods The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). Conclusions This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome

TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/2010. Daniel H. Solomon received support for this work from the NIH (K24-AR-055989). Elizabeth W. Karlson received support for this work from NIH (K24-AR-AR0524). Reuma.pt received unrestricted grants from Abbott, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, and UCB Pharma

Computed tomography myocardial perfusion vs (15)O-water positron emission tomography and fractional flow reserve

Objectives: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with ¹⁵O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). Methods: 51 patients (63 (61–65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by “snapshot” adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. Results: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32–2.20) vs 3.11 (2.44–3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32–2.20) vs 3.12 (2.44–3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71–76) vs 86 (84–88) HU, P < 0.001 and 101 (96–106) vs 111 (107–114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. Conclusion: CT myocardial attenuation density correlates with ¹⁵O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. Key Points: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from “snapshot” imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with ¹⁵O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve

Prevalence of physical activity through the practice of sports among adolescents from Portuguese speaking countries

This study evaluated the prevalence of physical activity through the practice of sports in adolescents from schools in two Brazilian cities and a Portuguese school, and its association with independent variables, such as gender and age. A cross-sectional study was conducted of schoolchildren from two cities in Brazil and one in Portugal. The total study sample was 3694 subjects (1622 males and 1872 females). Physical activity levels were assessed using Baecke's questionnaire. Body weight was measured on electronic scales and stature was measured with a portable wooden stadiometer. Numerical variables were expressed as mean, categorical variables were expressed as percentages and the chi-square test analyzed associations. The prevalence of no sport was high (39.7%), being higher in the Portuguese school than in the Brazilian schools (p < 0.001). Irrespective of being an adolescent in a Brazilian or Portuguese school, boys showed higher engagement in sports practice than girls (p < 0.001). In both, differences were identified between adolescents aged 13 to 15 (P = 0.001) and 16 to 17 (P = 0.001). The prevalence of physical inactivity among schoolchildren from two cities in Brazil and a school in Portugal was high, with the girls practicing less sport than the boys and with this imbalance likely to be higher in adolescents