Three-dimensional flow in Kupffer's Vesicle.

Whilst many vertebrates appear externally left-right symmetric, the arrangement of internal organs is asymmetric. In zebrafish, the breaking of left-right symmetry is organised by Kupffer's Vesicle (KV): an approximately spherical, fluid-filled structure that begins to form in the embryo 10 hours post fertilisation. A crucial component of zebrafish symmetry breaking is the establishment of a cilia-driven fluid flow within KV. However, it is still unclear (a) how dorsal, ventral and equatorial cilia contribute to the global vortical flow, and (b) if this flow breaks left-right symmetry through mechanical transduction or morphogen transport. Fully answering these questions requires knowledge of the three-dimensional flow patterns within KV, which have not been quantified in previous work. In this study, we calculate and analyse the three-dimensional flow in KV. We consider flow from both individual and groups of cilia, and (a) find anticlockwise flow can arise purely from excess of cilia on the dorsal roof over the ventral floor, showing how this vortical flow is stabilised by dorsal tilt of equatorial cilia, and (b) show that anterior clustering of dorsal cilia leads to around 40 % faster flow in the anterior over the posterior corner. We argue that these flow features are supportive of symmetry breaking through mechano-sensory cilia, and suggest a novel experiment to test this hypothesis. From our new understanding of the flow, we propose a further experiment to reverse the flow within KV to potentially induce situs inversus.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00285-016-0967-

Non-extremal black holes from the generalised r-map

We review the timelike dimensional reduction of a class of five-dimensional theories that generalises 5D, N = 2 supergravity coupled to vector multiplets. As an application we construct instanton solutions to the four-dimensional Euclidean theory, and investigate the criteria for solutions to lift to static non-extremal black holes in five dimensions. We focus specifically on two classes of models: STU-like models, and models with a block diagonal target space metric. For STU-like models the second order equations of motion of the four-dimensional theory can be solved explicitly, and we obtain the general solution. For block diagonal models we find a restricted class of solutions, where the number of independent scalar fields depends on the number of blocks. When lifting these solutions to five dimensions we show, by explicit calculation, that one obtains static non-extremal black holes with scalar fields that take finite values on the horizon only if the number of integration constants reduces by exactly half.Comment: 22 pages. Based on talk by OV at "Black Objects in Supergravity School" (BOSS2011), INFN, Frascati, Italy, 9-13 May, 201

Efeitos antiangiogênicos in vivo convalidam a atividade antineoplásica potencial do metiljasmonato

Molecular plant components have long been aimed at the angiogenesis and anti-angiogenesis pathways, and have been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. Jasmonate derivatives were demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16F10), while micromolar concentrations were ineffective. In vivo, comparable concentrations were toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 µM concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organised than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.Moléculas de origem vegetal são, há muito, conhecidas como substâncias ativas sobre as vias de angiogênese e antiangiogênese e foram testadas como fonte de drogas antineoplásicas com sucesso promissor. Este trabalho trata dos efeitos antiangiogênicos do Metiljasmonato, um protótipo da família dos derivados do ácido jasmônico, que danificam seletivamente a mitocôndria de células neoplásicas. In vitro, metiljasmonato 1-10 mM promoveu a morte celular de células endoteliais humanas de cordão umbilical (HUVEC) e de melanoma murino (B16F10); concentrações micromolares foram inócuas. In vivo, concentrações equivalentes foram tóxicas e reduziram a densidade de vasos em membranas corioalantoicas de embrião de galinha (CAM). Entretanto, concentrações entre 1-10 µM produziram um efeito complexo. Ocorreu aumento no brotamento capilar, mas os novos vasos apresentaram-se frágeis e menos organizados que os controles correspondentes. Sugere-se que, além da toxicidade direta contra as células tumorais, a ação do metiljasmonato sobre a angiogênese seja relevante para seu efeito antineoplásico

Supersymmetric Janus solutions in five and ten dimensions

We explicitly truncate N = 8 gauged supergravity in five dimensions to its SU(3)-invariant sector with dilaton and axion fields. We show that this truncation has a solution which is identical to the super Janus constructed in N = 2 gauged supergravity in five dimensions. Then we lift the solution of the SU(3)-invariant truncation to type IIB supergravity by employing the consistent truncation ansatz. We show that the lifted solution falls into a special case of the supersymmetric Janus solutions constructed in type IIB supergravity. Additionally, we also prove that the lifted solution provides a particular example of the consistent truncations of type IIB supergravity on Sasaki-Einstein manifolds.Comment: 32 pages, 2 figures, version published in JHE

Deletions of specific exons of FHOD3 detected by next-generation-sequencing are associated with hypertrophic cardiomyopathy

Despite new strategies, such as evaluating deep intronic variants and new genes in whole-genome-sequencing studies, the diagnostic yield of genetic testing in hypertrophic cardiomyopathy (HCM) is still around 50%. FHOD3 has emerged as a novel disease-causing gene for this phenotype, but the relevance and clinical implication of copy-number-variations (CNVs) have not been determined. In this study, CNVs were evaluated using a comparative depth-of-coverage strategy by NGS in 5493 hypertrophic cardiomyopathy probands and 2973 disease-controls. We detected three symmetrical deletions in FHOD3 that involved exons 15 and 16 in three HCM families (no CNVs were detected in the control group). These exons are part of the diaphanous inhibitory domain of FHOD3 protein, considered a cluster of mutations for HCM. The clinical characteristics of the affected carriers were consistent with those reported in FHOD3 in previous studies. This study highlights the importance of performing CNV analysis systematically in NGS genetic testing panels for HCM, and reinforce the relevance of the FHOD3 gene in the disease. This article is protected by copyright. All rights reserved

The unwarped, resolved, deformed conifold: fivebranes and the baryonic branch of the Klebanov-Strassler theory

We study a gravity solution corresponding to fivebranes wrapped on the $S^2$ of the resolved conifold. By changing a parameter the solution continuously interpolates between the deformed conifold with flux and the resolved conifold with branes. Therefore, it displays a geometric transition, purely in the supergravity context. The solution is a simple example of torsional geometry and may be thought of as a non-K\"ahler analog of the conifold. By U-duality transformations we can add D3 brane charge and recover the solution in the form originally derived by Butti et al. This describes the baryonic branch of the Klebanov-Strassler theory. Far along the baryonic branch the field theory gives rise to a fuzzy two-sphere. This corresponds to the D5 branes wrapping the two-sphere of the resolved conifold in the gravity solution.Comment: 41 pages, 7 figure

Power electronics converters for an electric vehicle fast charging station with storage capability

Fast charging stations are a key element for the wide spreading of Electric Vehicles (EVs) by reducing the charging time to a range between 20 to 40 min. However, the integration of fast charging stations causes some adverse impacts on the Power Grid (PG), namely by the huge increase in the peak demand during short periods of time. This paper addresses the design of the power electronics converters for an EV DC fast charging station with local storage capability and easy interface of renewables. In the proposed topology, the energy storage capability is used to smooth the peak power demand, inherent to fast charging systems, and contributes to the stability of the PG. When integrated in a Smart Grid, the proposed topology may even return some of the stored energy back to the power grid, when necessary. The accomplishment of the aforementioned objectives requires a set of different power electronics converters that are described and discussed in this paper.This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and by FCT within the Project Scope: UID/CEC/00319/2013. This work is financed by the ERDF – COMPETE 2020 Programme, and FCT within project SAICTPAC/0004/2015‐POCI‐01‐0145–FEDER‐016434 and FCT within project PTDC/EEI-EEE/28813/2017. Mr. Luis A. M. Barros is supported by the doctoral scholarship PD/BD/143006/2018 granted by the Portuguese FCT agency. Mr. Tiago Sousa is supported by the doctoral scholarship SFRH/BD/134353/2017 granted by the Portuguese FCT agency

Study design and baseline characteristics of patients on dialysis in the ASCEND-D trial

BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety. METHODS: We report the trial design, key demographic, clinical, and laboratory findings, and baseline therapies of 2964 patients randomised in the open-label (sponsor-blinded) active-controlled, parallel-group, randomised ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large cardiovascular outcome trials (CVOTs) and in the most relevant registries. RESULTS: The median age of patients was 58 years, 43% were female; 67% were white and 16% were black. The median haemoglobin at baseline was 10.4 g/dL. Among randomised patients, 89% were receiving haemodialysis and 11% peritoneal dialysis. Among key co-morbidities, 42% reported a history of diabetes mellitus, and 45% a history of cardiovascular disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron use was noted in 64% and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries. CONCLUSION: ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anaemia with CKD G5D

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure