Eph kinases and their ligands ephrins act in concert with sex hormones in regulating blood pressure

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN.

A lower bound for the energy of symmetric matrices and graphs

The energy of a symmetric matrix is the sum of the absolute values of its eigenvalues. We introduce a lower bound for the energy of a symmetric partitioned matrix into blocks. This bound is related to the spectrum of its quotient matrix. Furthermore, we study necessary conditions for the equality. Applications to the energy of the generalized composition of a family of arbitrary graphs are obtained. A lower bound for the energy of a graph with a bridge is given. Some computational experiments are presented in order to show that, in some cases, the obtained lower bound is incomparable with the well known lower bound $2\sqrt{m}$, where $m$ is the number of edges of the graph.

Avalição de desempenho de protocolos de autenticação para redes sem fio heterogêneas

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Elétrica, 2016.

EXPLICIT WRITTEN CORRECTIVE FEEDBACK AND LANGUAGE APTITUDE IN SLA: IMPLICATIONS FOR IMPROVEMENT OF LINGUISTIC ACCURACY

Most second language researchers agree that there is a role for corrective feedback in second language writing classes. However, many unanswered questions remain concerning which linguistic features to target and the type and amount of feedback to offer. This study examined two new pieces of writing by 151 learners of English as a Second Language (ESL), in order to investigate the effect of direct and metalinguistic written feedback on errors with the simple past tense, the present perfect tense, dropped pronouns, and pronominal duplication. This inquiry also considered the extent to which learner differences in language-analytic ability (LAA), as measured by the LLAMA F, mediated the effects of these two types of explicit written corrective feedback. Learners in the feedback groups were provided with corrective feedback on two essays, after which learners in all three groups completed two additional writing tasks to determine whether or not the provision of corrective feedback led to greater gains in accuracy compared to no feedback. Both treatment groups, direct and metalinguistic, performed better than the comparison group on new pieces of writing immediately following the treatment sessions, yet direct feedback was more durable than metalinguistic feedback for one structure, the simple past tense. Participants with greater LAA proved more likely to achieve gains in the direct feedback group than in the metalinguistic group, whereas learners with lower LAA benefited more from metalinguistic feedback. Overall, the findings of the present study confirm the results of prior studies that have found a positive role for written corrective feedback in instructed second language acquisition.

JOINT ENERGY BEAMFORMING AND TIME ASSIGNMENT FOR COOPERATIVE WIRELESS POWERED NETWORKS

Wireless power transfer (WPT) and radio frequency (RF)-based energy har- vesting arouses a new wireless network paradigm termed as wireless powered com- munication network (WPCN), where some energy-constrained nodes are enabled to harvest energy from the RF signals transferred by other energy-sufficient nodes to support the communication operations in the network, which brings a promising approach for future energy-constrained wireless network design. In this paper, we focus on the optimal WPCN design. We consider a net- work composed of two communication groups, where the first group has sufficient power supply but no available bandwidth, and the second group has licensed band- width but very limited power to perform required information transmission. For such a system, we introduce the power and bandwidth cooperation between the two groups so that both group can accomplish their expected information delivering tasks. Multiple antennas are employed at the hybrid access point (H-AP) to en- hance both energy and information transfer efficiency and the cooperative relaying is employed to help the power-limited group to enhance its information transmission throughput. Compared with existing works, cooperative relaying, time assignment, power allocation, and energy beamforming are jointly designed in a single system. Firstly, we propose a cooperative transmission protocol for the considered system, where group 1 transmits some power to group 2 to help group 2 with information transmission and then group 2 gives some bandwidth to group 1 in return. Sec- ondly, to explore the information transmission performance limit of the system, we formulate two optimization problems to maximize the system weighted sum rate by jointly optimizing the time assignment, power allocation, and energy beamforming under two different power constraints, i.e., the fixed power constraint and the aver- age power constraint, respectively. In order to make the cooperation between the two groups meaningful and guarantee the quality of service (QoS) requirements of both groups, the minimal required data rates of the two groups are considered as constraints for the optimal system design. As both problems are non-convex and have no known solutions, we solve it by using proper variable substitutions and the semi-definite relaxation (SDR). We theoretically prove that our proposed solution method can guarantee to find the global optimal solution. Thirdly, consider that the WPCN has promising application potentials in future energy-constrained net- works, e.g., wireless sensor network (WSN), wireless body area network (WBAN) and Internet of Things (IoT), where the power consumption is very critical. We investigate the minimal power consumption optimal design for the considered co- operation WPCN. For this, we formulate an optimization problem to minimize the total consumed power by jointly optimizing the time assignment, power allocation, and energy beamforming under required data rate constraints. As the problem is also non-convex and has no known solutions, we solve it by using some variable substitutions and the SDR method. We also theoretically prove that our proposed solution method for the minimal power consumption design guarantees the global optimal solution. Extensive experimental results are provided to discuss the system performance behaviors, which provide some useful insights for future WPCN design. It shows that the average power constrained system achieves higher weighted sum rate than the fixed power constrained system. Besides, it also shows that in such a WPCN, relay should be placed closer to the multi-antenna H-AP to achieve higher weighted sum rate and consume lower total power.

Holomorphic functions on non-Runge domains and related problems.

Let U be a domain in CN that is not a Runge domain. We study the topological and algebraic properties of the family of holomorphic functions on U which cannot be approximated by polynomials.

Simulación de esquemas de encolamiento

En este capítulo se presenta el proceso realizado para simular diferentes esquemas de encolamiento (FIFO, PQ y LLQ) de manera básica con el fin de ofrecer QoS en una red. También se presentan gráficas que permiten realizar el análisis posterior de los datos obtenidos en la simulación.

Towards a unified management of applications on heterogeneous clouds

The diversity in the way cloud providers o↵er their services, give their SLAs, present their QoS, or support di↵erent technologies, makes very difficult the portability and interoperability of cloud applications, and favours the well-known vendor lock-in problem. We propose a model to describe cloud applications and the required resources in an agnostic, and providers- and resources-independent way, in which individual application modules, and entire applications, may be re-deployed using different services without modification. To support this model, and after the proposal of a variety of cross-cloud application management tools by different authors, we propose going one step further in the unification of cloud services with a management approach in which IaaS and PaaS services are integrated into a unified interface. We provide support for deploying applications whose components are distributed on different cloud providers, indistinctly using IaaS and PaaS services.

Geospatial Data Indexing Analysis and Visualization via Web Services with Autonomic Resource Management

With the exponential growth of the usage of web-based map services, the web GIS application has become more and more popular. Spatial data index, search, analysis, visualization and the resource management of such services are becoming increasingly important to deliver user-desired Quality of Service. First, spatial indexing is typically time-consuming and is not available to end-users. To address this, we introduce TerraFly sksOpen, an open-sourced an Online Indexing and Querying System for Big Geospatial Data. Integrated with the TerraFly Geospatial database [1-9], sksOpen is an efficient indexing and query engine for processing Top-k Spatial Boolean Queries. Further, we provide ergonomic visualization of query results on interactive maps to facilitate the user’s data analysis. Second, due to the highly complex and dynamic nature of GIS systems, it is quite challenging for the end users to quickly understand and analyze the spatial data, and to efficiently share their own data and analysis results with others. Built on the TerraFly Geo spatial database, TerraFly GeoCloud is an extra layer running upon the TerraFly map and can efficiently support many different visualization functions and spatial data analysis models. Furthermore, users can create unique URLs to visualize and share the analysis results. TerraFly GeoCloud also enables the MapQL technology to customize map visualization using SQL-like statements [10]. Third, map systems often serve dynamic web workloads and involve multiple CPU and I/O intensive tiers, which make it challenging to meet the response time targets of map requests while using the resources efficiently. Virtualization facilitates the deployment of web map services and improves their resource utilization through encapsulation and consolidation. Autonomic resource management allows resources to be automatically provisioned to a map service and its internal tiers on demand. v-TerraFly are techniques to predict the demand of map workloads online and optimize resource allocations, considering both response time and data freshness as the QoS target. The proposed v-TerraFly system is prototyped on TerraFly, a production web map service, and evaluated using real TerraFly workloads. The results show that v-TerraFly can accurately predict the workload demands: 18.91% more accurate; and efficiently allocate resources to meet the QoS target: improves the QoS by 26.19% and saves resource usages by 20.83% compared to traditional peak load-based resource allocation.

Left atrial appendage: anatomy and imaging landmarks pertinent to percutaneous transcatheter occlusion

Percutaneous left atrial appendage (LAA) closure represents a complementary option and effective treatment for patients at risk of thromboembolism, especially in patients for whom it may be difficult to achieve satisfactory anticoagulation control or where anticoagulation treatment is not possible or desirable. Effective and safe transcatheter LAA occlusion requires a detailed knowledge of crucial anatomic landmarks and endocardial morphologic variants of the LAA and its neighbouring structures.1 ,2 w1–w3 Our aim in this article is to provide the basic anatomic information that is important for the interventional cardiologist to know when planning an LAA occlusion procedure.

Convergence time to equilibrium distributions of autonomous and periodic non-autonomous graphs

We present some estimates of the time of convergence to the equilibrium distribution in autonomous and periodic non-autonomous graphs, with ergodic stochastic adjacency matrices, using the eigenvalues of these matrices. On this way we generalize previous results from several authors, that only considered reversible matrices.

Contributo para a caracterização morfométrica da raça de abelhas melíferas (Apis mellifera iberiensis) da região norte de Portugal

A necessidade de aprofundar o conhecimento sobre a morfologia da abelha melífera portuguesa (Apis mellifera iberiensis) originou o presente estudo. A amostragem definiu-se com base no banco de amostras existentes no Laboratório de Patologia Apícola da ESA-IPB, relativas ao ano de 2015. Cada amostra foi constituída por cinco obreiras adultas conservadas pelo frio (-18 °C). Foram analisadas 124 amostras distribuídas por 16 concelhos (aproximadamente oito por concelho) pertencentes aos distritos de Bragança e Vila Real. As medições efetuadas em cada uma das obreiras foram: peso (PA), comprimento (CA) e largura (LA) do corpo; comprimento (CAA) e largura (LAA) da asa anterior; comprimento (CAP) e largura da asa posterior (LAP); comprimento do fêmur (CF), da tíbia (CT), do basitarso (CBT), do tarso (CTA) e da probóscide (CP) e a largura do basitarso (LBT). Para avaliação destas medidas utilizou-se uma balança analítica de precisão (0,01g) e um paquímetro eletrónico digital (0-100mm±0,02mm). As diferentes variáveis estudadas compararam-se por análise de variância (ANOVA), sendo o teste de Tukey-Kramer HSD utilizado para a comparação múltipla de médias. O peso médio das obreiras do concelho de Vila Pouca de Aguiar (0,123±0,018 g) foi mais elevado (p<0,05) do que o das obreiras dos concelhos de Torre de Moncorvo e Ribeira de Pena (0,106±0,023 g em ambos os casos). Também, as obreiras do concelho de Vila Pouca de Aguiar apresentaram um comprimento médio do corpo (13,065±0,890 mm) superior (p<0,05) às obreiras do concelho de Boticas (12,228±0,958 mm) e uma largura média (4,565 ± 0,392 mm) superior às obreiras de Vila Flor (4,089 ±0,288 mm). Porém, o CAP (6,333±0,303 mm) e o CT (3,179±0,183mm) das obreiras de Vila Pouca de Aguiar foi mais baixo (p<0,05) ao observado nos concelhos de Torre de Moncorvo (6,616±0,361 mm) e Vila Flor (3,358±0,146 mm). As variáveis LAA, LAP, CF, CBT e CP não apresentaram diferenças significativas (p>0,05) entre os concelhos estudados.

Constraint Programming-based Job Dispatching for Modern HPC Applications

A High-Performance Computing job dispatcher is a critical software that assigns the finite computing resources to submitted jobs. This resource assignment over time is known as the on-line job dispatching problem in HPC systems. The fact the problem is on-line means that solutions must be computed in real-time, and their required time cannot exceed some threshold to do not affect the normal system functioning. In addition, a job dispatcher must deal with a lot of uncertainty: submission times, the number of requested resources, and duration of jobs. Heuristic-based techniques have been broadly used in HPC systems, at the cost of achieving (sub-)optimal solutions in a short time. However, the scheduling and resource allocation components are separated, thus generates a decoupled decision that may cause a performance loss. Optimization-based techniques are less used for this problem, although they can significantly improve the performance of HPC systems at the expense of higher computation time. Nowadays, HPC systems are being used for modern applications, such as big data analytics and predictive model building, that employ, in general, many short jobs. However, this information is unknown at dispatching time, and job dispatchers need to process large numbers of them quickly while ensuring high Quality-of-Service (QoS) levels. Constraint Programming (CP) has been shown to be an effective approach to tackle job dispatching problems. However, state-of-the-art CP-based job dispatchers are unable to satisfy the challenges of on-line dispatching, such as generate dispatching decisions in a brief period and integrate current and past information of the housing system. Given the previous reasons, we propose CP-based dispatchers that are more suitable for HPC systems running modern applications, generating on-line dispatching decisions in a proper time and are able to make effective use of job duration predictions to improve QoS levels, especially for workloads dominated by short jobs.

Development of a patient-specific model for stroke risk assessment in atrial fibrillation patients

Atrial fibrillation is associated with a five-fold increase in the risk of cerebrovascular events,being responsible of 15-18% of all strokes.The morphological and functional remodelling of the left atrium caused by atrial fibrillation favours blood stasis and, consequently, stroke risk. In this context, several clinical studies suggest that stroke risk stratification could be improved by using haemodynamic information on the left atrium (LA) and the left atrial appendage (LAA). The goal of this study was to develop a personalized computational fluid-dynamics (CFD) model of the left atrium which could clarify the haemodynamic implications of atrial fibrillation on a patient specific basis. The developed CFD model was first applied to better understand the role of LAA in stroke risk. Infact, the interplay of the LAA geometric parameters such as LAA length, tortuosity, surface area and volume with the fluid-dynamics parameters and the effects of the LAA closure have not been investigated. Results demonstrated the capabilities of the CFD model to reproduce the real physiological behaviour of the blood flow dynamics inside the LA and the LAA. Finally, we determined that the fluid-dynamics parameters enhanced in this research project could be used as new quantitative indexes to describe the different types of AF and open new scenarios for the patient-specific stroke risk stratification.

Analisi dei parametri fluidodinamici calcolati tramite simulazione dell'occlusione dell'auricola sinistra e della dislocazione del dispositivo in condizioni di fibrillazione atriale.

La fibrillazione atriale (FA) è la forma di aritmia cardiaca più diffusa nella pratica clinica. Attualmente, sono più di 30 milioni le persone affette da FA e si prevede una forte crescita di tale numero, conseguentemente al progressivo invecchiamento della popolazione. Ad oggi, la terapia anticoagulante orale è la principale strategia impiegata per la prevenzione di ictus ischemico. Nonostante l’efficacia degli anticoagulanti, un numero rilevante di pazienti non possono assumerli, a causa di un aumentato rischio emorragico e della pericolosa interazione con altri farmaci. È stato dimostrato che nel 90% dei casi la formazione dei trombi intracardiaci in pazienti con FA avviene in un punto ben preciso dell’atrio sinistro, ossia nell’auricola. Ciò è dovuto al fatto che essa, avendo una particolare morfologia, in condizioni non fisiologiche (emodinamica rallentata), tende a favorire la stasi del sangue al suo interno. Di conseguenza, la chiusura meccanica dell’auricola è emersa come alternativa clinica alla prevenzione farmacologica. I risultati relativi a recenti trials hanno suggerito che la chiusura percutanea della LAA attraverso l’impianto di opportuni occlusori è una terapia sicura, con un’efficacia non inferiore alla terapia di anticoagulanti orali nella prevenzione dell’ictus. L’obiettivo di questo elaborato di tesi è valutare in simulazione l’effetto dell’occlusione dell’auricola sinistra e di un eventuale dislocazione del dispositivo sulla fluidodinamica atriale in pazienti affetti da FA. Sono stati realizzati modelli 3D che simulano sia il risultato della procedura di LAAO con i dispositivi Amulet e Watchman, sia l’effetto della dislocazione dell’occlusore. Successivamente, sono state effettuate le simulazioni fluidodinamiche CFD sui modelli di atrio intero, sui modelli occlusi (privi di auricola) e sui modelli parzialmente occlusi (dislocazione Amulet) per studiare e valutare i parametri fluidodinamici (velocità, vorticità e stasi).