Chez l’homme, la primo-infection par le vírus Herpès simplex de type 1 (HSV-1) a lieu au niveau de la muqueuse oro-pharyngée. Après une phase de réplication, les virions pénètrent les terminaisons axonales et migrent vers le ganglion trijumeau ipsilatéral (TG), puis vers le TG controlatéral. Le virus entre alors dans un état de latence dans les 2 TG. Les réactivations d’HSV-1 dans ces neurones sont responsables des kératites herpétiques (KH), unilatérales et survenant toujours du même côté chez un patient donné.En utilisant un modèle murin oro-oculaire, qui reproduit les aspects essentiels de la maladie chez l’homme, nous avons précédemment démontré que l’inoculation virale latéralisée d’un côté de la bouche entraine une réplication virale dans la lèvre, suivie d’une KH ipsilatérale à l’inoculation 6 jours plus tard. De manière concomitante, le virus se propage aux 2 TG, mais les réactivations ne surviennent que du côté ipsilatéral à l’inoculation. Nous avons également observé qu’après une primo-infection dans une lèvre avec une souche d’HSV-1 non-neurovirulente, les souris étaient protégées contre les signes de la maladie et contre la réactivation d’une souche sauvage pleinement virulente inoculée secondairement dans l’autre lèvre (souche ré-infectante). Afin de comprendre les mécanismes immunitaires en jeu dans cet état de protection, nous avons combiné une analyse en cytométrie en flux multiparamétrique à des tests immunologiques, pour quantifier et définir l’infiltrat immunitaire hématopoïétique et les chémokines inflammatoires au site d’inoculation et dans les TG. Nous avons démontré qu’après une inoculation unique avec la souche sauvage virulente, un infiltrat immun riche en cellules pro-inflammatoires, survenaient de manière retardée dans les lèvres inoculées, et persistaient dans les TG. A l’opposé, l’infiltrat immunitaire était plus précoce dans les tissus réinfectés (après une primo-infection par la souche non neurovirulente), plus riche en cellules de l’immunité adaptative, et associé à des concentrations moindres de chémokines inflammatoires. En outre, cet infiltrat s’estompait plus rapidement, avec une disparition concomitante des chémokines inflammatoires. Ces données permettent de mieux comprendre la nature et la cinétique de la réponse immunitaire anti-HSV-1, et pourront être utiles pour le développement futur de stratégies vaccinales anti-HSV-1. / In humans, Herpes simplex virus type 1 (HSV-1), primary infection occurs in the oral mucocutaneous tissues. Virions replicated here penetrate sensitive neuronal axons, migrate to both trigeminal ganglion (TG) where it established a lifelong latency. Reactivations of HSV-1 in the TG neurons induce clinical recurrences in the connected peripheral tissues. This process is involved in herpes simplex keratitis (HSK), a condition that, strikingly, occurs almost exclusively in the same eye for a given patient. Based on an experimental oro-ocular (OO) model of HSV-1 infection, that recapitulates most of these human clinical features, we previously demonstrated that a virus inoculation on one side of the mouth, leads to viral replication in the lip, followed by HSK. Virus concomitantly disseminates to both TG, but reactivation only occurs in the TG ipsilateral to the inoculation site. We also observed that after a primary inoculation with a non-neurovirulent strain of HSV-1 in one lip, mice are protected against both acute phase disease and reactivation after a superinfection with a fully virulent wild-type strain of HSV-1 in the contralateral lip.In order to understand the underlying mechanisms involved in this state of protection, we combined high resolution flow cytometry and bead-based immunoassays, to quantify hematopoietic subsets and inflammatory chemokines in the site of inoculation and in the TG. We demonstrated that after a single inoculation with the wild-type strain, a delayed immune infiltrate, boasting more proinflammatory subsets, occurred in the lip and persisted in the TG. In contrast, the immune infiltrate occurred earlier in the superinfected lip and ipsilateral TG, with less inflammatory chemokines but more adaptive immune subsets. Moreover, cellular infiltrate resolved faster, correlating with nullification of inflammatory chemokines locally. These data show that immune response kinetics influence the development of natural immunity to HSV-1, and can be harnessed to protect against disease and reactivations.

Problem behavior can interfere with teaching and learning. Developing interventions for problem behavior may be more efficient when the function of problem behavior is known. A variety of functional analysis (FA) methods have been developed to provide information on the variables maintaining problem behavior. Unfortunately most of the current adaptations of the FA are not always feasible for classroom teachers, or suited to a typical school day. The trial-based FA is an adaptation that increases the accessibility of FA in educational settings, but typically relies on occurrence measures. The use of latency as a measure may improve the sensitivity of the trial-based FA. This study extends the literature on adaptations to the functional analysis, specifically for use in the classroom, by using latency as a measure of response strength in the trial-based FA.

In the 21th century, we see a trend in which CPU processing power is not evolving at the same pace as it did in the century before. Also, in the current generation, the data requirements and the need for higher speed are increasing every day. This increasing demand requires multiple middlebox instances in order to scale. With recent progress in virtualization, middleboxes are getting virtualized and deployed as software (Network Function (NF)s) behind commodity CPUs. Various systems perform Load Balancing (LB) functionality in software, which consumes extra CPU at the NF side. There are research work in the past which tried to move the LB functionality from software to hardware. Majority of hardware­based load balancer only provides basic LB functionality and depends on NF to provide the current performance statistics. Providing statistics feedback to LB consumes processing power at the NF and creates an inter­dependency.   In this thesis work, we explore the possibility of moving the load balancing functionality to a Smart Network Interface Card (smartNIC). Our load balancer will distribute traffic among the set of CPUs where NF instances run. We will use P4 and C programming language in our design, which gives us the combination of high­speed parallel packet processing and the ability to implement relatively complex load balancing features. Our LB approach uses latency experienced by the packet as an estimate for the current CPU loading. In our design, higher latency is a sign of a more busy CPU. The Latency Aware smartNIC based Load Balancer (LASLB) also aims to reduce the tail latency by moving traffic from CPUs where traffic experiences high latency to CPU that processes traffic under low latency. The approach followed in the design does not require any statistics feedback support from the NF, which avoids the tight binding of LB with NF.   Our experiment on different traffic profiles has shown that LASLB can save ~30% CPU for NF. In terms of fairness of CPU loading, our evaluation indicates that in imbalanced traffic, the LASLB can load more evenly than other evaluated methods in smartNIC­ based LB category. Our evaluation also shows that LASLB can reduce 95th percentile tail latency by ~22% compared to software load balancing.

No description available.

Encryption is the process of obfuscating data to restrict access to it while allowing it to be returned to its original non-obfuscated form through decryption. This process is increasingly used within web-based systems to secure data. When encryption is introduced in a system, the overall end-to-end latency of the system typically increases, and this increase depends on the size of the input data given to the encryption algorithm. Arguably, the latency introduced by encryption can be reduced if data sizes can be reduced before encryption. Lossless compression is the process of taking some data and reducing its overall data footprint. Introducing such a process within a web-based system that uses encryption could have the potential of reducing overall end-to-end latency within the system, both by reducing encryption time and data transfer time. This thesis evaluates whether the introduction of compression can reduce end-to-end latency in a web-based file upload system that encrypts the received files before storage. A series of experiments have been performed on a created file upload system where compression has been implemented to be used before upload and encryption. The results of these experiments show that compression can reduce end-to-end latency within web-based file upload systems that use encryption by approximately 39% for upload scenarios and approximately 49% for download scenarios when running in a system configuration with network latency.

Latency is a common issue found in robotics teleoperation that is not currently addressed in simulation. This study examined the effects of latency on operator performance for a robot teleoperation navigation task. Operators used a Logitech gamepad controller to teleoperate a robot through both a simulated environment and real-world environment. Both environments had the same dimensions and provided a path with obstacles the participant had to navigate. Participants performed this navigation task under three latency conditions, zero, low and high. Completion time, number of collisions, NASA-TLX, System Usability Survey, and User Experience survey were collected and participant performance compared for all latency conditions across the simulated and real-world environments. Results indicated a significant difference in participant performance between the simulated and real-world scenarios.

Human Immunodeficiency Virus 1 (HIV-1) remains a significant public health concern due to the lack of a cure. In spite of anti-retroviral therapies, HIV-1 persists within infected cells as integrated transcriptionally silent proviruses. Re-activation after therapy interruption results in new HIV-1 replication. Attempts to clear this reservoir through the use of latency reversing agents by targeting cellular mechanisms that maintain HIV-1 in a latent state have been unsuccessful. In addition, subsets of latently infected cells exist within the reservoir that display differential capacities for provirus induction. In order to understand the nature of the reservoir and manipulate it therapeutically, more knowledge is needed regarding factors that bias a virus towards latency or replication at the time of infection. Because multiple mechanisms that regulate HIV-1 transcription, including chromatin remodeling, transcription factor activation and polymerase pausing, are regulated by the T cell receptor (TCR), I hypothesized that signaling at the time of infection determines proviral fate. I transduced Jurkat cell lines and primary CD4+ T cells with chimeric antigen receptors (CARs) that mimicked signaling from the TCR. These CARs spanned a 3-log range of binding affinities for their ligand, providing a tunable model. High levels of TCR stimulation during infection biased cells towards productive replication and the formation of an inducible latent reservoir. Examination of the mechanisms downstream from TCR signaling revealed that robust cellular activation led to a release of the repressor Negative Elongation Factor from the paused RNA Polymerase II, facilitating transcriptional elongation. Because signaling determined the presence of repressive factors, I sought to manipulate the balance between latency and expression through recruitment of repressors to the HIV-1 provirus using a nuclease-deficient CRISPR Associated Protein 9 fused to a Krüppel Associated Box Domain. I screened a pool of guide RNAs that mediated transcriptional repression of HIV-1. Our lab discovered that guides bound to the HIV-1 Long Terminal Repeat prevented viral re-activation in an integrated cell model of HIV-1 latency. The research presented here confirms my hypothesis that signals during infection have prolonged effects on latency reversal. I provide evidence that manipulation of these mechanisms represent therapeutic targets for cure efforts.

The relationship between accommodation and myopia has been under investigation for many years, and the effort to understand it is ongoing. In this thesis, an introduction to the state of myopia research is given first, with particular reference to studies of accommodation and higher-order ocular aberrations, which feature in the subsequent chapters. Following a brief introduction to the general technique of aberrometry and visual stimulus control using adaptive optics, the development of a monocular adaptive optics instrument for this purpose is described. The instrument is used to vary a dioptric stimulus and record the accommodation response in pilot studies and a detailed experiment, which has also been published elsewhere. It is found, among other things, that accommodation can respond to more than one different input level during its latency period, and that such inputs can be stored until components of the accommodation control system are free to process them. Indications of a minimum halting time for accommodation, of around 0.6 s, are presented. In later chapters, the development and testing of a new, binocular adaptive optics apparatus will be found. As well as binocular aberrometry and adaptive optics control of stimulus aberrations, this instrument displaces images to allow for and stimulate ocular convergence in binocular accommodation experiments. It is the first instrument in the world with its combined functionalities. Finally, the contribution of this thesis is summarised, and further instrumentation development and experiments are put forward for the continuation of this branch of accommodation and myopia research.

Physical constrains of integrated circuits (commonly called chip) in regards to size and finite number of wires, has made the design of System-on-Chip (SoC) more interesting to study in terms of finding better solutions for the complexity of the chip-interconnections. The SoC has hundreds of Processing Elements (PEs), and a single shared bus can no longer be acceptable due to poor scalability with the system size. Networks on Chip (NoC) have been proposed as a solution to mitigate complex on-chip communication problems for complex SoCs. They consists of computational resources in the form of PE cores and switching nodes which allow PEs to communicate with each other. In the design and development of Networks on Chip, performance modelling and analysis has great theoretical and practical importance. This research is devoted to developing efficient and cost-effective analytical tools for the performance analysis and enhancement of NoCs with m-port n-tree topology under bursty traffic. Recent measurement studies have strongly verified that the traffic generated by many real-world applications in communication networks exhibits bursty and self-similar properties in nature and the message destinations are uniformly distributed. NoC's performance is generally affected by different traffic patterns generated by the processing elements. As the first step in the research, a new analytical model is developed to capture the burstiness and self-similarity characteristics of the traffic within NoCs through the use of Markov Modulated Poisson Process. The performance results of the developed model highlight the importance of accurate traffic modelling in the study and performance evaluation of NoCs. Having developed an efficient analytical tool to capture the traffic behaviour with a higher accuracy, in the next step, the research focuses on the effect of topology on the performance of NoCs. Many important challenges still remain as vulnerabilities within the design of NoCs with topology being the most important. Therefore a new analytical model is developed to investigate the performance of NoCs with the m-port n-tree topology under bursty traffic. Even though it is broadly proved in practice that fat-tree topology and its varieties result in lower latency, higher throughput and bandwidth, still most studies on NoCs adopt Mesh, Torus and Spidergon topologies. The results gained from the developed model and advanced simulation experiments significantly show the effect of fat-tree topology in reducing latency and increasing the throughput of NoCs. In order to obtain deeper understanding of NoCs performance attributes and for further improvement, in the final stage of the research, the developed analytical model was extended to consider the use of virtual channels within the architecture of NoCs. Extensive simulation experiments were carried out which show satisfactory improvements in the throughput of NoCs with fat-tree topology and VCs under bursty traffic. The analytical results and those obtained from extensive simulation experiments have shown a good degree of accuracy for predicting the network performance under different design alternatives and various traffic conditions. / Libyan Ministry of Higher Education

No description available.