Os herpesvírus são normalmente adaptados a um único grupo de hospedeiros, e esta associação parasita-hospedeiro está ligada à sua seleção e coevolução. Estes agentes podem causar infecções latentes, onde normalmente o vírus não se replica. Durante o ciclo lítico, no entanto, outras células são infectadas e liberam partículas virais capazes de infectar outros indivíduos. O CFPHV (Chelonid fibropapilloma-associated herpesvirus) tem sido apontado como principal agente infeccioso ligado a fibropapilomatose em tartarugas-marinhas. A doença caracteriza-se por uma proliferação cutânea benigna mas que, dependendo da sua severidade, pode comprometer a sobrevivência do indivíduo afetado, sendo por isso apontada como importante ameaça a conservação de tartarugas-marinhas, particularmente de tartarugas verdes (Chelonia mydas), a principal espécie acometida pela doença. Alguns aspectos da biologia do CFPHV e sua relação com as tartarugas verdes foram estudados no presente trabalho. Primeiramente, a capacidade deste agente em se disseminar pelo ambiente e infectar outros indivíduos, e as possíveis vias envolvidas nesta dispersão. Em seguida, avaliou-se os possíveis tecidos em que o herpesvírus pode estabelecer a infecção latente. Por fim, determinou-se a prevalência de indivíduos de Chelonia mydas infectados pelo CFPHV em duas áreas de alimentação (Ubatuba-SP e Vitória-ES) e em uma áreas mista - de alimentação e reprodução (Fernando de Noronha-PE). No primeiro estudo, observou-se que a prevalência de CFPHV nas amostras de secreções de Chelonia mydas variou entre 0%, no Espírito Santo, a 25%, em São Paulo. Os haplótipos afetados foram CMA-3 e CMA-8, e a variante viral encontrada não havia sido detectada anteriormente no Brasil, mas possui elevada similaridade com vírus provenientes do Golfo da Guiné e de Porto Rico. Os resultados sugerem que estes vírus podem ser transmitidos por secreções e também circular entre diferentes regiões. No segundo estudo, detectou-se a presença de CFPHV no cérebro de 5 animais necropsiados e também na pele e em lesões fibropapilomatosas. Em um dos animais foi detectada a presença de uma única variante de CFPHV no cérebro, pele e tumores. Esta variante ainda não havia sido detectada no Brasil e apresentou 100% de identidade com a variante detectada nas secreções. Para avaliar a relação entre haplótipos e variantes virais, o terceiro estudo determinou a prevalência de CFPHV em pele e tumores de 136 indivíduos - 9,56% de indivíduos sadios apresentavam o agente em tecido epitelial e 45,58% dos animais foram positivos para CFPHV, quando considerados também animais com fibropapilomatose. Duas novas variantes de herpesvírus foram encontradas: Var. 7, em Ubatuba-SP e Vitória-ES e Var. 8, em Vitória-ES. Não houve associação entre uma variante viral e um haplótipo. Os resultados observados permitem apontar que o CFPHV pode estabelecer infecções latentes; o vírus pode \"migrar\" entre diferentes regiões, junto com seus hospedeiros; partículas virais podem ser liberadas por secreções; duas novas variantes foram identificadas. Altas taxas de substituição de nucleotídeos em CFPHV podem indicar o surgimento das variantes destas áreas, mas a alta similaridade entre as variantes detectadas e àquelas de Porto Rico e Golfo da Guiné sugerem também a entrada de novas variantes na costa brasileira. / Herpesviruses are usually adapted to a single group of hosts, and this host-parasite association is linked to its selection and co-evolution. These agents can cause latent infections, where the virus usually does not replicate. During the lytic cycle, however, other cells are infected and release viral particles capable of infecting other individuals.The CFPHV (Chelonid fibropapilloma-associated herpesviru) has been indicated as the main infectious agent linked to fibropapillomatosis on sea turtles. The disease is characterized by a benign skin proliferation, but, depending on its severity, can compromise the survival of the affected individual, therefore considered an important threat to the conservation of sea turtles, especially green turtles (Chelonia mydas), the main species affected by the disease. Some aspects of the CFPHV biology and its relation to green turtles were studied in this work. Firstly, the ability of this agent to spread in the environment and infect other individuals, and the possible pathways involved in this dispersion. Then, potential tissues wherein the herpesvirus can establish latent infection were assessed. Finally, we determined the prevalence of Chelonia mydas individuals infected by CFPHV in two feeding areas (Ubatuba-SP and Vitória-ES) and in a mixed area of feeding and reproduction (Fernando de Noronha-PE). In the first study, it was observed that the prevalence of CFPHV in samples of Chelonia mydas secretions ranged from 0% in Espírito Santo, to 25% in São Paulo. Affected haplotypes were CM-A3 and CM-A8, and viral variant found had not been previously detected in Brazil, but it is significantly similar to viruses found in the Gulf of Guinea and Puerto Rico. The results suggest that these viruses can be transmitted by secretions and can also circulate among different regions. Considering the low maintenance of the agent within the environment, they are probably brought by individuals with the latent virus, being capable of releasing viral particles during the herpesvirus replication cycle. In the second study, the presence of CFPHV was detected inside the brain of 5 necropsied animals, besides the detection of the virus on the skin and fibropapillomatosis lesions. In one of the animals, it was possible to characterize the CFPHV and the presence of a single viral variant inside the brain, tumors and on the skin of the same animal was detected. This variant had not yet been detected in Brazil and showed 100% identity with the variant detected in secretions. These results indicate that the virus may establish a latent infection in nerve tissue. To evaluate the relationship between haplotypes and viral variants, the third study determined the prevalence of CFPHV on skin and tumors of 136 individuals - 9.56% of healthy individuals showed the agent in epithelial tissue and 45.58% of the animals were positive for CFPHV, when also considered animals with fibropapillomatosis. Two new variants of the herpesvirus were found, Var. 7 in Ubatuba-SP and Vitória-ES and Var. 8 only in Vitória-ES. C. mydas individuals of different haplotypes were infected, and there was no association between a viral variant and a haplotype. The observed results permitted to point that CFPHV can establish latent infections in Chelonia mydas; the virus can \"migrate\" among different regions, along with its hosts; viral particles can be released by secretion; viral variants previously detected were not found in these areas, but two new variants were detected. The high nucleotide substitution rates observed in CFPHV may indicate the emergence of these variants in these areas, but the high similarity among the detected variants and those identified in Puerto Rico and Gulf of Guinea also suggest the entry of new variants into the Brazilian coast.

Orientador: Ibiara Correia de Lima Almeida Paz / Resumo: A avicultura de corte é caracterizada pelos ciclos de produção muito curtos, com rápido crescimento dos frangos. Em contrapartida, essa característica se reflete na composição mineral dos ossos e cartilagens, estando inaptos para sustentar seu peso, resultando em queda no desempenho e na produtividade, além de prejudicar o bem-estar animal. A hipótese dessa pesquisa foi de que os distúrbios ósseos causam prejuízo ao desenvolvimento do frango de corte e a qualidade de sua carcaça, e esses problemas começam a surgir com o aumento exponencial do ganho de peso. O objetivo desse trabalho foi correlacionar as metodologias de avaliação de bem-estar em frangos de corte por meio da capacidade de manter-se em pé em caixas plásticas (versão adaptada do latency to lie) e caminhar no trajeto em um metro linear (gait score), delineando a idade e o peso que se iniciam os distúrbios locomotores. Somado a isso, foi verificado a incidência de miopatia dorsal cranial, pododermatite e distúrbios locomotores nas aves. Para tanto, foram utilizadas 1000 aves da linhagem Cobb® Slow, adquiridas de um incubatório comercial, com 1 dia de idade, e alojadas em um sistema totalmente automatizado com ventilação em pressão negativa, utilização de exaustores e painéis evaporativos de celulose. Para este estudo, não houve tratamento, delineamento e repetição, assim, avaliou-se os animais em condições semelhantes às comerciais de criação. O bem-estar foi avaliado por dois métodos distintos, o gait score e o la... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Poultry farming is characterized by very short production cycles, with rapid growth of chickens. In contrast, this characteristic is reflect in the mineral composition of bones and cartilage, being unable to sustain their weight, resulting in a drop in performance and productivity, as well as impairing animal welfare. The hypothesis of this research was that the bone problems cause damage to the development of the broiler chicken and the quality of its carcass, and these problems begin to appear with the exponential increase of the weight gain. The objective of this study was to correlate welfare methodologies in broiler chickens through the ability to stand in plastic boxes (adapted version of latency to lie) and walk on a linear meter (gait score), delineating the age and weight that locomotion problems begin. In addition, the incidence of dorsal cranial myopathy, pododermatitis and locomotion problems in birds was verified. For this purpose, 1000 birds of the Cobb® Slow lineage were used, acquired from a commercial hatchery, at 1 day of age, housed in a fully automated system with negative pressure ventilation, use of hoods and evaporative cellulose panels. For this study, there was no treatment, delineation and repetition, thus, the animals were evaluated under conditions similar to commercial ones. The welfare was evaluated by two distinct methods, gait score and latency to lie, and later these methods were compared and correlated. The birds were weighed weekly, in order... (Complete abstract click electronic access below) / Mestre

"Due to the dramatic growth in the use of Wireless Sensor Network (WSN) applications - ranging from environment and habitat monitoring to tracking and surveillance, network research in WSN protocols has been very active in the last decade. With battery-powered sensors operating in unattended environments, energy conservation becomes the key technique for improving WSN lifetimes. WSN Medium Access Control (MAC) protocols address energy awareness and reduced duty cycles since the radio is the component that consumes most of the energy. This thesis investigates the performance of two recently published energy-aware MAC protocols, Crankshaft and SCP-MAC. Crankshaft has been shown to be one of the best protocols in terms of energy consumption in dense WSNs while SCP-MAC has a dedicated low duty cycle and low average latencies. The focus of this investigation is to discover techniques for reducing the latency of Crankshaft. Using OMNeT++, an open source and component-based simulation framework, this study investigates possible modifications to Crankshaft to improve its latency. The potential improvements considered include modifications to Crankshaft’s retransmission contention scheme (Sift), adjustments to its inherent settings, and investigating the impact of ACKs. Since OMNeT++ readily provided only a variant of SCP-MAC identified as SCP-MAC*, the simulations results presented involve comparing variants of both protocols (Crankshaft and SCP-MAC*). The performance of these protocols is also analyzed using distinct sensor node communication patterns. It was determined that Crankshaft’s latency depends on its ACK/Retransmission settings. Specifically, Crankshaft has the best latency with No ACKs, without much loss in energy consumption. But the latency can also be improved when ACKs are enabled by reducing the number of retries. Furthermore, the latency and delivery ratio are also directly governed by the WSN traffic pattern and the congestion in the network, as there was a noticeable improvement for both parameters in one-hop traffic, compared to multi-hop convergecast traffic to the sink. Finally, it was observed that Crankshaft’s broadcast performance in flooding traffic can be improved by increasing the number of broadcast slots used, though this is detrimental to its performance in unicast traffic."

Human cytomegalovirus (HCMV) is a betaherpesvirus which establishes a lifelong persistent infection, underpinned by its ability to establish latent infection in early myeloid lineage cells, in the infected host. Although well controlled by a healthy immune system, HCMV causes pathological and life threatening disease in individuals with a compromised or immature immune response, which can come from primary HCMV infection or reactivation of latent infection. Although progress is being made in understanding the mechanisms by which HCMV maintains latency and reactivates, a better understanding is essential towards the aim of targeting and killing latently infected cells. In this thesis, I will present evidence that the HCMV-encoded chemokine receptor homologue US28, which is expressed during latent infection of CD14+ monocytes, is necessary for maintaining HCMV latency in these monocytes and, in the absence of US28 protein expression, HCMV undergoes lytic infection. US28 expression was found to attenuate cellular signalling pathways in latently infected cells; in particular, MAP kinase and NFκB. Interestingly, deletion of the US28 gene or inhibition of the US28 protein resulted in the expression of lytic antigens which allowed detection of infected monocytes by the immune system. This observation may lead to a potential new immunotherapeutic strategy against latent HCMV. Having demonstrated that US28 protein is expressed on the surface of latently infected monocytes, I tested whether a new fusion-toxin protein, called F49A-FTP, which binds US28 protein, could be used to target and kill latently infected cells. I developed a protocol for treating latently infected monocytes with F49A-FTP which resulted in a significant reduction in virus reactivation after monocyte differentiation to dendritic cells. I was also able to show that this treatment kills CD34+ progenitor cells, which were experimentally latently infected with HCMV, as well as latently infected monocytes from a healthy, seropositive blood donor. Finally, during my investigations into the role of US28 during HCMV latency, a mass spectrometry screen was performed to measure changes in cellular protein expression when US28 protein is expressed in isolation, in THP-1 monocyte-like cell line. This identified CTCF, a transcription factor which appears to be modified by US28 in THP-1 cells. I showed that CTCF has a repressive effect on the HCMV MIEP, and that CTCF likely plays a role in HCMV latency. In summary, this work provides insights into the role of US28 during HCMV latency, and proposes potential novel therapeutic strategies to kill latently infected cells.

Le virus de l’herpès simplex de type 1 (HSV1) établit une infection latente dans le système nerveux de l'homme, au cours de laquelle un type de transcrits, appelés LATs (pour latency associated transcripts), s'accumule dans les neurones infectés. Le rôle clef des LATs dans le contrôle de la latence virale est reconnu. Cependant, depuis leur découverte dans les années 80, leur mécanisme d'action reste non élucidé.Le gène des LATs est transcrit en un LAT primaire de 8,3kb, qui est épissé, conduisant à la formation de deux LATs stables : le LAT2kb et le LAT1.5kb. De façon remarquable, le LAT2kb et le LAT1.5kb sont des introns. Leur stabilité est la conséquence d'un branchement non canonique qui se traduit par le maintien de la structure en lariat. Par ailleurs, la région du génome codant les LATs contient également le gène RL2 qui code ICP0, la protéine la plus en amont dans la cascade de réactivation du virus. Des études précédentes ont montré qu’au moment de la latence, des transcrits RL2 non épissés, s'accumulent au site principal de la latence (le ganglion de Gasser).Nous avons caractérisé ces transcrits non épissés du gène RL2 dans les tissus infectés de façon latente. Ils contiennent de façon reproductible l’intron 1 et sont d’autant plus abondants dans les tissus infectés de façon latente que les LAT s’accumulent. On peut ainsi distinguer plusieurs types de tissus infectés de façon latente, dont les deux exemples les plus représentatifs sont d’une part le ganglion de Gasser (forte expression des LAT et accumulation de transcrits RL2 non-épissés) et d’autre part le ganglion cervical supérieur (pas d’accumulation de LAT par rapport aux quantités exprimées pendant la phase aiguë de l’infection, et très peu d’expression dans transcrits non-épissés). Dans tous les cas, la réalité du caractère latent de l’infection était confirmé par la présence de génome viral sans expression de transcrits matures de gène viral précoce (représenté par celui de la thymidine kinase) ni tardif (gène UL18). Ces résultats suggèrent une relation entre la présence des LAT et l’accumulation de transcrits RL2 non-épissés, ce qui pourrait être en relation avec le maintien de l’infection à l’état latent dans ces tissus. / The herpes simplex virus type 1 (HSV-1) establishes a latent infection in the nervous system of humans, in which latency associated transcripts (LATs) accumulate in infected neurons. The key role of LATs in the control of viral latency is well established. However, since their discovery in the 80s, their mechanism of action remains unclear.The LAT gene is transcribed into a 8.3 kb primary LAT that is rapidly spliced, leading to the formation of two stable LATs; LAT2kb and LAT1.5kb. Remarkably, the LAT2kb and LAT1.5kb are introns. Their stability is the result of a non-canonical sequence of the branching point, which results in maintaining the lariat structure.Moreover, the region of the genome encoding the LATs also contains the RL2 gene, encoding ICP0 that acts upstream in the cascade of viral reactivation. Previous studies have shown that RL2 unspliced transcripts may accumulate in the main site of HSV-1 latency (trigeminal ganglia). We have characterized these unspliced transcripts RL2 gene in latently infected tissues. They reproducibly contain intron 1 and are particularly abundant in latently infected tissues where LATs also accumulate. We distinguished several types of latently infected tissues, the two most representative examples being the trigeminal ganglion (strong expression of LATs and accumulation of non-spliced transcripts RL2) and, in the opposite, the superior cervical ganglion (no accumulation of LAT compared with the amounts expressed during the acute phase of infection, and little expression in non-spliced RL2 transcripts). In all cases, the reality of the latent nature of the infection was confirmed by the presence of viral genome with no expression of mature transcripts from early viral gene (represented by the thymidine kinase gene) or late (UL18 gene).These results suggest a relationship between the presence of LAT and the accumulation of non-spliced RL2 transcripts, which could be related to the maintenance of latent infection in these tissues.

ARQUIVO 2.0 – des_memórias fotográficas é uma pesquisa na linha de Poéticas Visuais que trata do conceito de latência a partir de arquivos fotográficos disponíveis on-line. Abordando processos de criação que investigam a imagem e seus desdobramentos em meios, procedimentos e tecnologias, explorase relações entre palavras e fotos, a partir de duas séries: DELETE.use e RASTER. Em DELETE.use (2013-2015), a latência é investigada através da supressão da figura humana em clássicos da fotografia, procurando ressignificações para imagens de vários gêneros. Já em RASTER (2012-2016), a latência é analisada através de interferências sobre os códigos estruturais de arquivos fotográficos digitais. Nas duas séries, procurou-se criar estratégias para manipular, expor e compartilhar fotografias notórias, observando questões relacionadas com apropriação e coautorias, processos artísticos colaborativos, tradução e deslocamento de sentidos para arquivos fotográficos digitais, que culminaram na formulação do conceito de des_memória, como um estado poético e transitório, que influi nos modos de ver e falar sobre fotografia como um bem cultural. / ARCHIVE 2.0 - photographic des_memórias is a research in Visual Poetics line dealing with the concept of latency, from photographic archives available online. Addressing creation processes that investigate the image and its developments in media, procedures and technologies, explores relationships between words and photos, from two series: DELETE.use and RASTER In DELETE.use (2013-2015), the concept of latency is investigated by eliminating the human figure in photography classics, looking reinterpretation of images of various genres. Already RASTER (2012-2016), latency is analyzed by interference on the structural codes of digital photo files. In both series, we tried to create strategies to manipulate, display and share notorious photographs, observing issues related to ownership and coauthorships, collaborative artistic processes, translation and displacement directions for digital photo archives, which culminated in the formulation of the concept of des_memory as a poetic and transient state, that influence the ways of seeing and talking about photograph as a cultural asset.

Relying on computing systems that become increasingly complex is difficult: with many factors potentially affecting the result of a computation or its properties, understanding where problems appear and fixing them is a challenging proposition. Typically, the process of finding solutions is driven by trial and error or by experience-based insights. In this dissertation, I examine the idea of using provenance metadata (the set of elements that have contributed to the existence of a piece of data, together with their relationships) instead. I show that considering provenance a primitive of computation enables the exploration of system behaviour, targeting both retrospective analysis (root cause analysis, performance tuning) and hypothetical scenarios (what-if questions). In this context, provenance can be used as part of feedback loops, with a double purpose: building software that is able to adapt for meeting certain quality and performance targets (semi-automated tuning) and enabling human operators to exert high-level runtime control with limited previous knowledge of a system's internal architecture. My contributions towards this goal are threefold: providing low-level mechanisms for meaningful provenance collection considering OS-level resource multiplexing, proving that such provenance data can be used in inferences about application behaviour and generalising this to a set of primitives necessary for fine-grained provenance disclosure in a wider context. To derive such primitives in a bottom-up manner, I first present Resourceful, a framework that enables capturing OS-level measurements in the context of application activities. It is the contextualisation that allows tying the measurements to provenance in a meaningful way, and I look at a number of use-cases in understanding application performance. This also provides a good setup for evaluating the impact and overheads of fine-grained provenance collection. I then show that the collected data enables new ways of understanding performance variation by attributing it to specific components within a system. The resulting set of tools, Soroban, gives developers and operation engineers a principled way of examining the impact of various configuration, OS and virtualization parameters on application behaviour. Finally, I consider how this supports the idea that provenance should be disclosed at application level and discuss why such disclosure is necessary for enabling the use of collected metadata efficiently and at a granularity which is meaningful in relation to application semantics.

Telecom service providers are adopting a Network Functions Virtualization (NFV) based service delivery model, in response to the unprecedented traffic growth and an increasing customers demand for new high-quality network services. In NFV, telecom network functions are virtualized and run on top of commodity servers. Ensuring network performance equivalent to the legacy non-virtualized system is a determining factor for the success of telecom networks virtualization. Whereas in virtualized systems, achieving carrier-grade network performance such as low latency, high throughput, and high availability to guarantee the quality of experience (QoE) for customer is challenging. In this thesis, we focus on addressing the latency challenge. We investigate the delay overhead of virtualization by comprehensive network performance measurements and analysis in a controlled virtualized environment. With this, a break-down of the latency incurred by the virtualization and the impact of co-locating virtual machines (VMs) of different workloads on the end-to-end latency is provided. We exploit this result to develop an optimization model for placement and provisioning of the virtualized telecom network functions to ensure both the latency and cost-efficiency requirements. To further alleviate the latency challenge, we propose a multipath transport protocol MDTCP, that leverage Explicit Congestion Notification (ECN) to quickly detect and react to an incipient congestion to minimize queuing delays, and achieve high network utilization in telecom datacenters. / HITS, 4707

The U.S. National Market System (NMS), the largest marketplace in the world for securities and exchange traded funds, suffers from geographic market fragmentation which leads to reduced market efficiency. Communication lines transmit price updates and other information between geographically isolated exchanges at varying speeds, bounded above by the speed of light. Market participants have access to federally mandated information provided by the Securities Information Processor (SIP) and privately offered information provided by the exchanges, often called direct feeds. These feeds are quantitatively and qualitatively distinct, with the direct feeds tending to provide more information at a faster rate than the SIP feed. Differences between the SIP and direct feeds can lead to information asymmetries between market participants, which in turn create arbitrage opportunities. Under the market conditions of the NMS in 2016, these arbitrage opportunities occur regularly and many can be captured by market participants with fast connectivity. Several methods exist which allow market participants to reduce their communication latency with trading centers, including the practice of co-location where market participants pay to have their trading infrastructure located in the same building as the matching engines of an exchange. Such regularly occurring and executable arbitrage opportunities run counter to the Efficient-Market Hypothesis (EMH) in all forms, where even the weak form of the EMH claims that market participants should not be able to systematically profit from market inefficiencies. This thesis investigates the market inefficiencies and related effects introduced by geographic market fragmentation in two baskets of stocks: the Dow Jones Industrial Average (Dow), and the 30 largest stocks by market capitalization in the Standard \& Poor's 500 index (S&P 30).

Mechanical loading can modulate tissue plasticity and has potential applications in rehabilitation science and regenerative medicine. To safely and effectively introduce mechanical loads to human cells, tissues, and the entire body, we need to understand the optimal loading environment to promote growth and health. The purpose of this research was 1) to validate a limb vibration and compression system; 2) to determine the effect of limb vibration on neural excitability measured by sub-threshold TMS-conditioned H-reflexes and supra-threshold TMS; 3) to determine changes in center of pressure, muscle activity, and kinematics during a postural task following limb vibration; 4) to determine the effect of vibration on accuracy and long latency responses during a weight bearing visuomotor task. The major findings of this research are 1) the mechanical system presented in the manuscript can deliver limb vibration and compression reliably, accurate, and safely to human tissue; 2) sub-threshold cortical stimulation reduces the vibration-induced presynaptic inhibition of the H-reflex. This reduction cannot be attributed to an increase in cortical excitability during limb vibration because the MEP remains unchanged with limb vibration; 3) limb vibration altered the soleus and tibialis EMG activity during a postural control task. The vibration-induced increase in muscle activity was associated with unchanged center of pressure variability and reduced center of pressure complexity; 4) healthy individuals were able to accommodate extraneous afferent information due to the vibration interventions They maintained similar levels of accuracy of a visuomotor tracking task and unchanged long latency responses during an unexpected perturbation.