Este trabalho teve por objetivo estudar aspectos de Qualidade de Serviço (QoS) na transmissão de áudio e vídeo por redes de grande abrangência geográfica (WANs). Dois cenários distintos foram estudados. No primeiro foi feita uma proposta de um método de gerenciamento que permite que computadores de uma rede local (LAN) equipados com interfaces Ethernet possam criar canais dinamicamente através de um backbone ATM para tráfego de voz e vídeo. Uma implementação do modelo foi avaliada para ilustrar a viabilidade do método proposto. No segundo cenário foi mostrado através de extensas simulações computacionais que o princípio da deflexão pode ser usado com êxito para oferecer QoS a aplicações em tempo real. Nestas simulações foi usado como exemplo prático uma aplicação de voz sobre IP (VoIP).

In ATM (asynchronous transfer mode) networks, rate-based regulation-scheduling (R&S) mechanisms guarantee certain quality of service (QoS) with controlling the rate of a tagged connection serviced by the switches. The R&S mechanisms, which consider only the issues of one tagged connection itself but the situation of the scheduling queue, can behave hand-over well. However, there may be many connections hand over in identical condition and compete for the position in the scheduler queue. It makes the transmission to be distorted greatly from the hand-over. There is already a scheme, dynamic R&S, to smooth rate jitter with counting the hand-over of other connections. Dynamic R&S doesn't count the idle slots, which also make the interval between two consecutive tagged cells, and results in unnecessary misses. The new scheme proposed considers the system time and scheduler queue's length. It has less difference between transmission intervals and the premised one of a tagged connection, so that is better in rate-jitter control. This mechanism has O(1) time-complexity, so conforms to the demand of high-speed ATM networks.

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Este trabalho teve por objetivo estudar aspectos de Qualidade de Serviço (QoS) na transmissão de áudio e vídeo por redes de grande abrangência geográfica (WANs). Dois cenários distintos foram estudados. No primeiro foi feita uma proposta de um método de gerenciamento que permite que computadores de uma rede local (LAN) equipados com interfaces Ethernet possam criar canais dinamicamente através de um backbone ATM para tráfego de voz e vídeo. Uma implementação do modelo foi avaliada para ilustrar a viabilidade do método proposto. No segundo cenário foi mostrado através de extensas simulações computacionais que o princípio da deflexão pode ser usado com êxito para oferecer QoS a aplicações em tempo real. Nestas simulações foi usado como exemplo prático uma aplicação de voz sobre IP (VoIP).

Background: Autophagy is a conserved physiological process in the body that functions to maintain homeostasis via degradation and recycling of dysfunctional proteins and even entire organelles. It is typically triggered by nutritional stress and/or growth factor deprivation and ultimately results in the packaging of cellular components into autophagosomes. These autophagosomes then fuse with lysosomes to be degraded. Autophagy is suggested to play a significant role in cardiac remodeling, particularly following myocardial infarction (MI). Ataxia-telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein activated in response to DNA damage. Mutations in ATM cause a multi-systemic disease known as Ataxia-telangiectasia (AT). The present study aims to investigate the relationship between ATM and autophagy in the heart, particularly post-MI. Methods: Wild-type (WT) and ATM heterozygous (hKO; aged ~4 months) were injected with either bafilomycin (Baf; autophagy inhibitor) or rapamycin (Rap; autophagy activator) for 30 minutes. MI was then induced mice by ligation of the left anterior descending coronary artery. Heart function was measured using M-mode echocardiography 4 hours post-MI. For cellular analysis of autophagy, confluent cultures of cardiac fibroblasts were isolated from adult male rats and treated with KU-55933 (KU; specific ATM inhibitor) in serum-free media for 4 hours. Cardiac fibroblasts were also isolated from ATM WT, heterozygous (hKO), and knockout (KO) mice, grown to confluency, and serum-starved for 4 hours. Levels of microtubule-associated protein light chain 3-II (LC3-II), a marker for autophagy, was examined in the heart and cell lysates using western blots. Results: M-mode echocardiography revealed that MI decreases heart function in both genotypes as measured by decreased %FS and EF. No change in heart function was observed between WT-MI and hKO-MI groups following Baf treatment. Rap treatment resulted in the functional recovery of the heart in WT-MI, not in hKO-MI group. Levels of LC3-II protein were higher in hKO-sham versus WT-sham hearts. MI decreased LC3-II protein in hKO-MI, not in WT-MI group. Baf treatment further decreased LC3-II protein levels in hKO-MI group. LC3-II levels were lower in KU-treated rat cardiac fibroblasts when compared to control. Cardiac fibroblasts isolated from hKO and KO hearts exhibited decreased LC3-II levels versus those isolated from WT hearts. Conclusion: Although further investigations are needed to confirm our findings, these data provide evidence that ATM deficiency hinders improvement in heart function post-MI following activation of autophagy. ATM deficiency results in reduced autophagy post-MI, an effect that appears to be exaggerated following autophagy inhibition. ATM deficiency also reduces autophagy in rat and mouse cardiac fibroblasts.

Cardiovascular diseases are the leading cause of mortality worldwide. Ataxia telangiectasia mutated kinase (ATM) is a checkpoint protein involved in cell cycle regulation. It is activated in response to genotoxic mediators such as double-stranded DNA damage or oxidative damage. Mutations in the ATM gene result in a multisystemic disease called ataxia-telangiectasia (A-T). Independently, a Western-type Diet (WD) and ATM protein deficiency are linked with heart disease, exacerbated cardiac remodeling, and myocardial infarction (MI). Our laboratory has previously shown that in male mice, the consumption of a WD during ATM deficiency is associated with the exacerbation of cardiac remodeling. This study investigated the effect of ATM deficiency on WD-induced cardiac remodeling parameters before and 1-day post-MI in a sex-specific manner using female and male mice. Age-matched wild-type (WT) and ATM heterozygous knockout (hKO) mice were fed with normal-chow (NC) or WD for 14 weeks. MI was induced by ligation of the left anterior descending coronary artery (LAD) with a 7-0 polypropylene suture. After the study period, 14 weeks post-WD feeding and 1-day post-MI, the heart was removed through an opening in the diaphragm region. Heart sections were stained with Masson's trichrome to quantify fibrosis, TUNEL-stained to quantify apoptosis, infarct size, and infarct thickness, and wheat germ agglutinin-stained to quantify myocyte hypertrophy. In WT female mice, WD increased myocardial fibrosis, myocyte hypertrophy, and apoptosis at baseline compared to NC. However, in hKO-WD female mice, apoptosis was significantly lower, and hypertrophy was significantly higher than in WT-NC female mice at baseline. Intriguingly, no significant difference in apoptosis, infarct size, and infarct thickness was observed in both genotypes and genders 1-day post-MI. Thus, our data suggest that 1) ATM deficiency plays a cardioprotective role in female mice responding to WD, as it reduces apoptosis and increases hypertrophy at baseline, and 2) sex-specific cardioprotective effects of ATM deficiency in female mice were not observed 1-day post-MI in response to WD.

Yes / A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis. / MRC program grant U1175.01.005.00005.01 from RSC and MRC centre grant G0801130 from JAC. / Erratum: 18 Apr 2016: Penedos A, Johnson AL, Strong E, Goldman AS et al (2016) Correction: Essential and Checkpoint Functions of Budding Yeast ATM and ATR during Meiotic Prophase Are Facilitated by Differential Phosphorylation of a Meiotic Adaptor Protein, Hop1. PLOS ONE. 11(4): e0154170. https://doi.org/10.1371/journal.pone.0154170.

Yes / In the section “Generation of phospho-specific Hop1 antibodies” of the Materials and Methods, we made several mistakes when indicating the sequence of the peptides used for the generation of antibodies. / Erratum: Penedos A, Johnson AL, Strong E, Goldman AS, Carballo JA, Cha RS (2015) Essential and Checkpoint Functions of Budding Yeast ATM and ATR during Meiotic Prophase Are Facilitated by Differential Phosphorylation of a Meiotic Adaptor Protein, Hop1. PLoS ONE 10(7): e0134297. doi: 10.1371/ journal.pone.0134297

Data traffic has emerged as a big challenge for the standardization of traffic management mechanisms in ATM networks. In April 1996 the ATM Forum published the first version of the Available Bit Rate Service Category (ABR) to give support to this kind of traffic. ABR was designed with ambitious objectives: high network efficiency, fairness and inter-operability of different ABR switch mechanisms.The major part of this PhD Thesis has been devoted to ABR. Instead of focusing on one aspect of ABR, the main research topics involved in ABR have been covered, namely: (i) switching mechanisms, (ii) conformance definition, (iii) charging, (iv) ABR support to TCP traffic. In the following the main conclusions are summarized. Maybe, switch algorithms have been the most investigated topic of ABR. This has happened because the specification of ABR given by the ATM Forum allows a diversity of switch algorithms to be implemented. These range from the simplest binary switches to the more complex ER switches. In the PhD Thesis three of these switch algorithms are analyzed by means of simulation, showing the different degree of performance and complexity that can be achieved. The behavior of ER switches is also analyzed by means of real traces obtained with a commercial ER switch. The conformance definition is the formalism established to decide whether the source transmits according to the traffic contract. The conformance algorithm standardized for ABR is the Dynamic Generic Cell Rate Algorithm (DGCRA). The PhD Thesis gives a detailed description of the DGCRA. Furthermore, traces obtained by simulation are depicted showing that the algorithm given by the ATM Forum has a decreasing accuracy of the rate conformance with increasing feedback delay. A "UPC based on the CCR" is proposed to solve this drawback. The parameter dimensioning of the DGCRA is addressed in the PhD Thesis by means of two analytical approaches. Numerical results calculated with the analytical models are also obtained by simulation for validation. The analytical approaches are based on a novel queuing model of the DGCRA. The first analytical approach is based on a renewal assumption of the cell inter-arrival process at the UPC. This approach gives a simple but coarse approximation of the cell rejection probability at the UPC. The second analytical method consists of a Markov chain that accurately describes the stochastic variables involved in the queuing model of the DGCRA. The Markov chain is solved applying the matrix geometric technique. The complexity of this mathematical approach only allows investigating a simple network topology. However, the accuracy of the model allows taking into account the influence of the delay bounds that are negotiated with the DGCRA. This study shows that a major degradation of the cell rejection probability may be obtained if these delay bounds are not properly set. Another issue investigated in the PhD Thesis is the charging of ABR. Charging may have a decisive impact on the deployment, success and growth of a network. In fact, the research community has paid a great attention to this topic in recent years. Furthermore, pricing may be an essential condition for the users when submitting traffic. Some authors have used this fact to propose congestion control mechanisms based on a dynamic pricing. In such schemes, prices vary according to the demand of network resources by the sources. New prices are conveyed to the sources by means of a feedback mechanism. This charging scheme seems to fit well with ABR, since the RM-cells can be used to dynamically communicate the prices. In the PhD Thesis a dynamic pricing scheme is proposed and an analytical model is used to find out the evolution of the prices. Additionally, several charging schemes are confronted by simulation. This comparison shows that the dynamic pricing gives the best expected charging. Finally, the support of ABR to the traffic generated with the TCP protocol used in the Internet is investigated by simulation. Currently, the data communications are dominated by the Internet traffic transported by a variety of networks. The deployment of ATM technology has been located in the backbone networks and the end-to-end ATM systems appear remote. In fact, it is not clear whether the universal multi-service network will be built on the Internet rather than the B-ISDN. Simulations performed in the PhD Thesis confront the transport of TCP traffic in different scenarios using ABR and the simpler UBR Service Category. The main conclusion is that ABR can solve the severe fairness problems that can arise using UBR.

Este trabalho apresenta um estudo dos mecanismos de policiamento de tráfego ATM (Asynchronous Transfer Mode) mais conhecidos e uma analise das condições de seu gerenciamento utilizando o protocolo SNMP (Simple Network Management Protocol). Para este fim foram considerados os objetos gerenciados integrantes de MIBs (Management Information Base) propostas por vários grupos de trabalho com o objetivo de averiguar a viabilidade de gerenciar o processo de policiamento de trafego mediante manipulação de tais objetos. Realizando este gerenciamento pode-se acompanhar o estado da rede e utilizar estas informações no planejamento da capacidade da rede, pois muitas vezes, o congestionamento não ocorre apenas por excesso de trafego e sim pelo mau dimensionamento dos componentes da rede de computadores. Foram estudados diversos mecanismos de controle de trafego e congestionamento. Estes mecanismos pertencem basicamente a dois procedimentos sugeridos pelo Fórum ATM: controle dos mecanismos de use/rede e controle de realimentação de fluxo. Os algoritmos estudados no processo de controle dos mecanismos de use/rede foram: balde furado, balde furado virtual, balde furado com memória, janelas saltitantes, janelas deslizantes, contadores de pico, escalonamento virtual, balde furado de estado continuo. No processo de controle de realimentação do fluxo existem dois mecanismos básicos: o credit-based e o rate-based. Como o segundo mecanismo foi melhor aceito internacionalmente, surgiram vários algoritmos que seguiam seus princípios. Entre eles pode-se citar: controle de fluxo baseado na taxa, controle de taxa explicita, VS/VD (Virtual Source Virtual Destination), PRCA (Proportional Rate Control Algorithm), EPRCA (Enhanced Proporcional Rate Control Algorithm), ERICA (Explicit Rate Indication for Congestion Avoidance) e CAPC (Congestion Avoidance using Proportional Control). Este trabalho estuda os dois mecanismos básicos assim como os algoritmos que seguem a filosofia rate-based. As MIBs inspecionadas para este trabalho foram: MIB da RFC 1695 [AHM 94], MIB dos objetos suplementares [LY 96], MIB da especificação UNI 3.1 do Fórum ATM[CHA 96], MIB da interface M4 do Fórum ATM [ATM 96] MIB da empresa Bay Networks [BAY 96] e MIBs da empresa Cisco [WAN 96] [CHA 96a], [GRO 96], [GRO 96a], [RBH 96] e [BAK 96]. Em resultado ao estudo dos mecanismos de controle de trafego e congestionamento e a análise das MIBs selecionadas, foram construídas tabelas que tentam relacionar os parâmetros necessários para controlar os mecanismos de tráfego e congestionamento com os objetos das MIBs selecionadas. A cada parâmetro de controle é verificado se existe um objeto gerenciado ou uma combinação de objetos que podem fornecer o valor do parâmetro. A partir desta análise é verificado se os objetos gerenciados podem monitorar os mecanismos de tráfego e congestionamento. / This work presents a study of the best known ATM traffic policing mechanism and an analysis of management conditions using the SNMP (Simple Network Management Protocol). For this reason the managed objects were considerated pertaining to MIBs (Management Information Base) proposed by many working groups. This work inquires the possibility of managing the traffic policing process using the objects of this selected MIBs. Realizing this management, it can follow the network state and to utilize these informations in the planning of network capacity, because many times, the congestion only not happen for traffic excess but it occurs by worse dimension of the computer networks components. It was studied many traffic and congestion control mechanisms. These mechanisms belong to two procedures proposed by the ATM Forum: usage/network parameter control and feedback control mechanism. The algorithms studied for the usage/network parameter control were: leaky bucket, virtual leaky bucket, buffered leaky bucket, jumping window, moving window, peak counters and generic cell rate algorithm. The feedback control has two variations: credit-based and rate-based. The second mechanism was better accepted internationally, and many algorithms followed its principles. The algorithms were: rate based flow control, explicit rate control, VS/VD (Virtual Source / Virtual Destination), PRCA (Proportional Rate Control Algorithm), EPRCA (Enhanced Proporcional Rate Control Algorithm), ERICA (Explicit Rate Indication for Congestion Avoidance) e CAPC (Congestion Avoidance using Proportional Control). This work studies the two basic mechanism and the rate-based algorithms. The inspected MIBs for this work were: RFC I695's MIB [AHM 94], definitions of supplemental managed objects for ATM management [LY 96], ATM Forum ATM UNI 3.1 Specification's MIB [CHA 96], ATM Forum M4 interface's MIB [ATM 96] , Bay Networks enterprise's MIB [BAY 96] and Cisco enterprise's MIB [WAN 96] [CHA 96a], [GRO 96], [GRO 96a], [RBH 96] e [BAK 96]. As a result of the study of the traffic and congestion control mechanisms and the analysis of selected MIBs, table were built that try to relate the necessary parameters to control traffic and congestion mechanisms with the managed objects. Each control parameter is examined if it has a managed object or a object arrangement that can supply the parameter value. This analysis will verify if managed objects can control traffic and congestion control.