Similar to cancer cells, HIV-infected cells differ from HIV-uninfected cells in that they have altered interferon signaling pathways, the apparent reason for the selectivity of certain oncolytic viruses (OVs). Therefore, it was hypothesized that use of an OV, such as recombinant Maraba virus (MG1), may be a potential approach to eliminate latently-infected cells constituting the HIV reservoir while sparing HIV-uninfected cells. This was studied in U1, ACH-2, OM-10 and J1.1 cells and their respective HIV-uninfected parent cell lines in addition to CD4+CD25-HLADR- cells from HIV-infected individuals on effective antiretroviral therapy. Although MG1 infected and killed latently HIV-infected U1 cells to a greater degree than the HIV-uninfected parent U937 cells, this was not observed in the other HIV-infected cell lines and their respective parent cell lines. Furthermore, results from primary cells suggest that MG1 alone does not appear to eliminate cells which comprise the major HIV reservoir. Challenges of studying the HIV reservoir and priorities for future studies examining the use of OVs as a potential strategy to eliminate the HIV reservoir are discussed.

Thesis (Ph. D.)--University of Nevada, Reno, 2005. / Includes bibliographical references. Online version available on the World Wide Web.

Data centres lie at the heart of almost every service on the Internet. Data centres are used to provide search results, to power social media, to store and index email, to host “cloud” applications, for online retail and to provide a myriad of other web services. Consequently the more efficient they can be made the better for all of us. The power of modern data centres is in combining commodity off-the-shelf server hardware and network equipment to provide what Google’s Barrosso and Ho ̈lzle describe as “warehouse scale” computers. Data centres rely on TCP, a transport protocol that was originally designed for use in the Internet. Like other such protocols, TCP has been optimised to maximise throughput, usually by filling up queues at the bottleneck. However, for most applications within a data centre network latency is more critical than throughput. Consequently the choice of transport protocol becomes a bottleneck for performance. My thesis is that the solution to this is to move away from the use of one-size-fits-all transport protocols towards ones that have been designed to reduce latency across the data centre and which can dynamically respond to the needs of the applications. This dissertation focuses on optimising the transport layer in data centre networks. In particular I address the question of whether any single transport mechanism can be flexible enough to cater to the needs of all data centre traffic. I show that one leading protocol (DCTCP) has been heavily optimised for certain network conditions. I then explore approaches that seek to minimise latency for applications that care about it while still allowing throughput-intensive applications to receive a good level of service. My key contributions to this are Silo and Trevi. Trevi is a novel transport system for storage traffic that utilises fountain coding to max- imise throughput and minimise latency while being agnostic to drop, thus allowing storage traffic to be pushed out of the way when latency sensitive traffic is present in the network. Silo is an admission control system that is designed to give tenants of a multi-tenant data centre guaranteed low latency network performance. Both of these were developed in collaboration with others.

All mammalian cells encode microRNAs (miRNAs), which are small non-coding RNAs (~ 22 nucleotides) that control numerous physiological processes via regulation of gene expression. A number of viruses, in particular herpesviruses, also encode miRNAs. Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi’s sarcoma associated herpesvirus (KSHV) are associated with lymphoproliferative disorders and some types of cancer in humans. Gammaherpesvirus-encoded miRNAs are predicted to contribute to pathogenesis and virus life cycle by suppressing host and viral target genes. However, the exact functions of these miRNAs during virus infection in the natural host are largely unknown. Strict species specificity has limited research on the human gammaherpesviruses mainly to in vitro studies. Murine gammaherpesvirus 68 (MHV-68) encodes at least 15 miRNAs and provides a unique tractable small animal model to investigate in vivo gammaherpesvirus pathogenic features that are difficult to assess in humans. Following intranasal infection of lab mice, the virus undergoes primary lytic infection in the lung epithelial cells and then spreads to the spleen establishing latent infection in splenic B lymphocytes, macrophages, and dendritic cells. The peak of the latent viral load occurs in the spleen at 14 dpi and then it decreases over time, but the virus is not completely eliminated and the latent viral genomes remain in the host cells for lifetime and can reactivate to produce infectious virus under certain conditions. The aims of my project were to: (1) establish and develop quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays for quantification of the MHV-68 miRNAs, (2) determine the miRNAs expression profiles during the two stages of virus infection (lytic and latent infection), (3) investigate the kinetics of the miRNAs expression during latency in vivo, (4) construct an MHV-68 miRNA mutant virus lacking 9 miRNAs (designated MHV-68.ΔmiRNAs), and (5) carry out thorough phenotypic characterisation of this mutant virus in order to determine the possible functions MHV-68 miRNAs in the context of natural host infection. It was found that the MHV-68 miRNAs expression pattern varied during different stages of infection, suggesting a differential regulation of the expression of these miRNAs depending on the phase of infection. In order to investigate the kinetics of miRNAs expression during latency in vivo, BALB/c mice were infected intranasally with MHV- 68 virus and spleens were harvested at days 10, 14, 21, and 32 post infection. The levels of miRNAs expression were determined by qRT-PCR in the splenocytes from infected mice. Interestingly, in contrast to the lytic MHV-68 protein coding genes, the expression of the miRNAs increased over time after 21 dpi, suggesting that the MHV-68-encoded miRNAs may play more fundamental roles during later stages of latent infection. In order to determine the potential roles of the MHV-68 miRNAs in virus pathogenesis, a miRNA mutant virus lacking the expression of 9 miRNAs, named MHV- 68.ΔmiRNAs, was constructed. The miRNA mutant virus replicated with the same kinetics as wild type virus in vitro and in vivo demonstrating that the deleted MHV-68 miRNAs are dispensable for virus lytic replication. To examine the roles of the miRNAs during virus latency, the MHV-68.ΔmiRNAs virus was characterised throughout a 49- day course of infection. Although the level of ex vivo reactivation of the MHV-68.ΔmiRNAs virus was comparable to that of the WT virus during the establishment of latency and as late as 28 dpi, the reactivation of the MHV-68.ΔmiRNAs virus was approximately 18-times higher than that of the WT virus at 49 dpi despite the similar levels of the genomic viral DNA loads at the same time-point. This suggests that the MHV-68 miRNAs suppress virus reactivation and promote maintenance of long-term latency. Moreover, the lytic viral gene expression levels were higher in splenocytes from the MHV-68.ΔmiRNAs-infected mice than the basal expression levels in the splenocytes from WT MHV-68-infected mice, suggesting that the MHV-68 miRNAs may suppress viral lytic gene expression during long-term latency in vivo and thus help the virus lay low.

abstract: Virtual machines and containers have steadily improved their performance over time as a result of innovations in their architecture and software ecosystems. Network functions and workloads are increasingly migrating to virtual environments, supported by developments in software defined networking (SDN) and network function virtualization (NFV). Previous performance analyses of virtual systems in this context often ignore significant performance gains that can be acheived with practical modifications to hypervisor and host systems. In this thesis, the network performance of containers and virtual machines are measured with standard network performance tools. The performance of these systems utilizing a standard 3.18.20 Linux kernel is compared to that of a realtime-tuned variant of the same kernel. This thesis motivates improving determinism in virtual systems with modifications to host and guest kernels and thoughtful process isolation. With the system modifications described, the median TCP bandwidth of KVM virtual machines over bridged network interfaces, is increased by 10.8% with a corresponding reduction in standard deviation of 87.6%. Docker containers see a 8.8% improvement in median bandwidth and 4.4% reduction in standard deviation of TCP measurements using similar bridged networking. System tuning also reduces the standard deviation of TCP request/response latency (TCP RR) over bridged interfaces by 86.8% for virtual machines and 97.9% for containers. Hardware devices assigned to virtual systems also see reductions in variance, although not as noteworthy. / Dissertation/Thesis / Masters Thesis Computer Science 2015

La latence, c'est-à-dire le délai entre l'action d'un utilisateur en entrée d'un système et la réponse correspondante fournie par le système, est un problème majeur pour l'utilisabilité des dispositifs interactifs. La latence est particulièrement perceptible pour l’interaction au toucher et détériore la performance de l'utilisateur même à des niveaux de l'ordre de la dizaine de millisecondes. Or, la latence des écrans tactiles actuels (smartphones ou tablettes) est en général supérieure à 70 ms.Notre objectif est d'améliorer nos connaissances sur la latence (ses causes, ses effets) et de trouver des méthodes pour la compenser ou en diminuer les effets négatifs. Nous proposons un état de l'art des travaux en IHM sur le sujet, puis nous effectuons un rapprochement avec la littérature du contrôle moteur qui a aussi étudié le comportement humain face à des perturbations visuomotrices et en particulier l’adaptation des mouvements à un retard du retour visuel.Nous détaillons ensuite nos quatre contributions. Nos résultats contribuent de manière à la fois pratique et théorique à la résolution du problème de la latence lors de l'interaction au toucher direct. Deux contributions complètent le diagnostic de la latence : la première est une nouvelle technique de mesure de latence; la seconde est une étude de l'effet de la latence sur l'interaction bimanuelle, importante pour l'interaction sur les grandes surfaces tactiles. Nous montrons que l'interaction bimanuelle est autant touchée par la latence que l'interaction à une main, ce qui suggère que des tâches plus complexes, qui augmenterait la charge cognitive, ne réduisent pas nécessairement l'effet de la latence. Nos deux autres contributions portent sur la réduction des effets de la latence. D'une part, nous proposons un système à faible latence (25 ms) associé à une compensation prédictive logicielle, et nous mettons en évidence que ce système permet d'améliorer la performance des utilisateurs comme s'ils utilisaient un système à 9 ms de latence. D'autre part nous étudions la capacité des utilisateurs à s'adapter à la latence pour améliorer leur performance sur une tâche de suivi de cible et nous montrons que l'impact négatif de la latence se réduit sur le long terme grâce aux capacités d'adaptation humaine. / Latency, the delay between a user input on a system and the corresponding response from the system, is a major issue for the usability of interactive systems. In direct-touch interaction, latency is particularly perceivable and alters user performance even at levels in the order of ten milliseconds. Yet, current touch devices such as smartphones or tablet-pc exhibit in general latencies over 70 ms.Our goal is to improve the knowledge on latency (its causes, its effects) and to find strategies to compensate it or to decrease its negative effects. We present a review of the HCI literature on the topic, then we link this literature with the motor control research field that has studied human behaviour when facing visuomotor perturbations, and in particular the adaptation to feedback delay.We then present our four contributions. We contribute both in a practical and a theoretical manner to the problem of latency in direct-touch interaction. Two of our contributions supplement the diagnosis of latency: the first one is a new latency measurement technique; the second one is a study of the impact of latency on bimanual interaction, which is important when interacting on large tactile surfaces. We show that bimanual interaction is as much affected by latency as a single hand interaction, suggesting that more complex tasks, suppose to increase the cognitive load, do not necessarily reduce the effect of latency. Our two other contributions address the reduction of the effects of latency. On one hand, we introduce a low latency system (25 ms) associated with a predictive software compensation, and we show that the system enables users to improve their performances as if they were using a system with 9 ms of latency. On the other hand we study users' ability to adapt to latency in order to improve their performance on a tracking task, and we show that the negative impact of latency is reduced with long-term training thanks to human adaptability.

O câncer é responsável por aproximadamente 13% de todas as mortes no mundo, sendo que elas ocorrem principalmente em pessoas que são diagnosticadas tardiamente e em estágios avançados. Devido às suas características devastadoras e à prevalência cada vez maior da doença, é inquestionável a necessidade de investigações e pesquisas constantes na área, no sentido de aprimorar a detecção precoce e auxiliar em sua prevenção e tratamento. Dentre as diversas abordagens existentes, uma alternativa é a criação de técnicas para estimar o período de crescimento \"silencioso\" do câncer, que significa conhecer o momento do início do processo cancerígeno, também chamado de período de latência. A partir da revisão da literatura realizada, foi verificada uma escassez de modelos que estimam a latência do câncer, indicando a necessidade de estudo sobre o tema. Nesse contexto, métodos de análise de sobrevivência surgem como uma ferramenta útil para a construção desses modelos. No presente trabalho, é apresentada uma revisão de um modelo já existente, bem como sua formulação e métodos de estimação. Além disso, apresenta-se uma aplicação em um conjunto de dados reais e uma discussão dos resultados obtidos.Foi identificada a necessidade da formulação de um novo modelo, visto que o método estudado apresenta algumas limitações. Com isso são apresentadas 3 alternativas de modelos que solucionam os pontos apresentados na discussão, com respectivas aplicações. / Cancer is responsible for about 13% of all deaths in the world occuring mainly in people who are late diagnosed and in advanced stages. Due to its devastating characteristics and the growing prevalence of the disease, it is unquestionable the need of constant investigation and research in this area, in order to improve the early detection and to help in its prevention and treatment. Among the existing approaches, one alternative is the creation of techniques to estimate the \"silent\" growth period of cancer, which means to know the beginning moment of the carcinogen period, also known as latency period. In a literature review, it was found an shortage of models that estimate the latency of cancer, indicating the need of study about this theme. In this context, survival analysis methods appear as an useful tool to build these models. In this study, a review of an existing model is presented, as well as its formulation and estimation methods. Furthermore, an application on real data and a discussion of the obtained results are made. As a result, it was identified the need to formulate a new model, because of the limitations of the studied one. We present 3 alternative models that solve the points presented in the discussion, with applications.

Firewalls are one of the essential tools to secure any network. IPtables has been the defacto firewall in all Linux systems, and the developers behind IPtables are alsoresponsible for its intended replacement, NFtables. Both IPtables and NFtables arefirewalls developed to filter packets. Some services are heavily dependent on lowlatency transport of packets, such as VoIP, cloud gaming, storage area networks andstock trading. This work is aiming to compare the latency between the selectedfirewalls while under generated network load. The network traffic is generated byiPerf and the latency is measured by using ping. The measurement of the latency isdone on ping packets between two dedicated hosts, one on either side of the firewall.The measurement was done on two configurations one with regular forwarding andanother with PAT (Port Address Translation). Both configurations are measured whileunder network load and while not under network load. Each test is repeated ten timesto increase the statistical power behind the conclusion. The results gathered in theexperiment resulted in NFtables being the firewall with overall lower latency bothwhile under network load and not under network load. / Brandväggen är ett av de viktigaste verktygen för att säkra upp nätverk. IPtables harvarit den främst använda brandväggen i alla Linux-system och utvecklarna bakomIPtables är också ansvariga för den avsedda ersättaren, NFtables. Både IPtables ochNFtables är brandväggar som utvecklats för att filtrera paket. Vissa tjänster är starktberoende av att paket som skickas anländer med låg latens. Tjänster som VoIP, cloudgaming, lagringsnät och aktiehandel. Detta arbete syftar till att jämföra latensenmellan de valda brandväggarna under en genererad nätverkslast. Nätverkslastengenereras av iPerf och latensen mäts med hjälp av ping. Mätningen av latensen görs påpingpaketen mellan två dedikerade värdar, en på vardera sida av brandväggen.Mätningen gjordes på två olika konfigurationer, en med vidarebefordran och en annanmed portadressöversättning (eng. PAT, Port Address Translation). Bådakonfigurationerna mäts både under nätverksbelastning och utan nätverksbelastning.Varje test upprepas tio gånger för att öka den statistiska signifikansen bakomslutsatsen. Resultaten som samlats in i experimentet visade att NFtables varbrandväggen med generell lägre latens både under last och inte under last.

The Internet of Things (IoT) is growing rapidly these years and the influence of IoT on everyday life and behavior are also increasing. It is a network that connects physical devices, vehicles, buildings, and other items and embedded with electronics, software, sensors, actuators, and network connectivity so that these objects can collect and exchange data. It has been utilized in lots of domains, such as transportation and logistics domain, healthcare domain, smart environment domain, personal and social domain. It is estimated that the IoT will consist of almost 50 billion objects by 2020. IoT Gateway is really important in IoT, which can bridge traditional communication networks with sensor networks to make the network communication easier. IoT communication is of vital importance in today’s life. This study has the aim of integrating and evaluating of IoT gateways and IoT communication systems. It proposes a scenario where the IoT gateway connects to an actuator in order to control the actuator and transmit the data via the IoT communication system, creates a demonstrator by setting up the communication between the IoT gateway platform and the IoT communication system, measures and evaluates the performance in terms of latency and throughput using the implemented scenario, and at last draws the conclusion.

The storage of frequently requested multimedia content at small-cell base stations (BSs) can reduce the load of macro-BSs without relying on high-speed backhaul links. In this work, the optimal operation of a system consisting of a cache-aided small-cell BS and a macro-BS is investigated for both offline and online caching settings. In particular, a binary fading one-sided interference channel is considered in which the small-cell BS, whose transmission is interfered by the macro-BS, has a limited-capacity cache. The delivery time per bit (DTB) is adopted as a measure of the coding latency, that is, the duration of the transmission block, required for reliable delivery. For offline caching, assuming a static set of popular contents, the minimum achievable DTB is characterized through information-theoretic achievability and converse arguments as a function of the cache capacity and of the capacity of the backhaul link connecting cloud and small-cell BS. For online caching, under a time-varying set of popular contents, the long-term (average) DTB is evaluated for both proactive and reactive caching policies. Furthermore, a converse argument is developed to characterize the minimum achievable long-term DTB for online caching in terms of the minimum achievable DTB for offline caching. The performance of both online and offline caching is finally compared using numerical results.