No description available.

Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet the underlying mechanism of this paradoxical phenomenon remains unclear. It is well known that tyrosine phosphorylation of most components of the IFN-I Jak-STAT pathway is essential for its signaling transduction. Thus, we have performed phosphotyrosine proteomics. We have found that the IFN-I Jak-STAT pathway is inactive due to the attenuated STAT2 activity, whereas the IFN-II Jak-STAT pathway is constitutively active, in EBV latency. We further confirmed these results by immunoblotting. This pilot study provides valuable information for the critical question regarding how the IRF7-mediated IFN-I response is evaded by EBV in its latency, and will prompt us to elucidate the underlying mechanisms.

MicroRNAs (miRNAs) function as key regulators in immune responses and cancer development. In the contexts of infection with oncogenic viruses, miRNAs are engaged in viral persistence, latency establishment and maintenance, and oncogenesis. In this review, we summarize the potential roles and mechanisms of viral and cellular miRNAs in the host-pathogen interactions during infection with selected tumor viruses and HIV, which include (i) repressing viral replication and facilitating latency establishment by targeting viral transcripts, (ii) evading innate and adaptive immune responses via toll-like receptors, RIG-I-like receptors, T-cell receptor, and B-cell receptor pathways by targeting signaling molecules such as TRAF6, IRAK1, IKKε, and MyD88, as well as downstream targets including regulatory cytokines such as tumor necrosis factor α, interferon γ, interleukin 10, and transforming growth factor β, (iii) antagonizing intrinsic and extrinsic apoptosis pathways by targeting pro-apoptotic or anti-apoptotic gene transcripts such as the Bcl-2 family and caspase-3, (iv) modulating cell proliferation and survival through regulation of the Wnt, PI3K/Akt, Erk/MAPK, and Jak/STAT signaling pathways, as well as the signaling pathways triggered by viral oncoproteins such as Epstein-Barr Virus LMP1, by targeting Wnt-inhibiting factor 1, SHIP, pTEN, and SOCSs, and (v) regulating cell cycle progression by targeting cell cycle inhibitors such as p21/WAF1 and p27/KIP1. Further elucidation of the interaction between miRNAs and these key biological events will facilitate our understanding of the pathogenesis of viral latency and oncogenesis and may lead to the identification of miRNAs as novel targets for developing new therapeutic or preventive interventions.

Real-time multimedia streaming is an extensively researched topic. The possibility of streaming video over the internet in real time requires smart solutions on many levels at the player and streamer side, as well as along the intermediate network. There are many different methods used to achieve this, but not all of them are suitable for the low latency real-time streaming needed for remote operations of vehicles. This thesis focuses on the bit-rate control at the streamer side to achieve low latency, meaning how the video quality is changed to adapt to the changes in the network. A literature study was conducted, in order to find what algorithms are currently being used for real-time streaming. It investigated both what control methods are used, as well as what feedback metrics are feed to these controllers. These approaches where then evaluated from a theoretical standpoint for real-time low latency streaming on 4G networks together with the rest of the assumed system. Using these discovered methods, two new algorithms were created. They were tested against an already existing benchmark controller, both in simulation and on a real network. As the benchmark algorithm proved to already be using all suitable feedback metrics, only small control alterations where done to the existing benchmark algorithm. The goal for the new algorithms was to increase the total throughput of the video stream, without decreasing the robustness and causing a higher latency.  Simulation and real network tests proved that the new algorithms are unable to provide a higher throughput without increasing the latency. The conclusion is that the benchmark controller is well designed and explicitly configured to work for the goal of low latency video streaming. This being the case with many controllers in the industry, as they are well designed and extensively trimmed for their specific task.

No description available.

Computer designers rely upon near-cycle-accurate microarchitectural simulation to explore the design space of new systems. Unfortunately, such simulators are becoming increasingly slow as systems become more complex. Hybrid simulators which offload some of the simulation work onto FPGAs can increase the speed; however, such simulators must be automatically synthesized or the time to design them becomes prohibitive. Furthermore, FPGA implementations of simulators may require multiple FPGA clock cycles to implement behavior that takes place within one simulated clock cycle, making correct arbitrary composition of simulator components impossible and limiting the amount of hardware concurrency which can be achieved. Latency-Insensitive Bounded Dataflow Networks (LI-BDNs) have been suggested as a means to permit composition of simulator components in FPGAs. However, previous work has required that LI-BDNs be created manually. This paper introduces techniques for automated synthesis of LI-BDNs from the processes of a System-C microarchitectural model. We demonstrate that LI-BDNs can be successfully synthesized. We also introduce a technique for reducing the overhead of LI-BDNs when the latency-insensitive property is unnecessary, resulting in up to a 60% reduction in FPGA resource requirements.

When humans and remote robots work together on a team, the robots always interact with a human supervisor, even if the interaction is limited to occasional reports. Distracting a human with robotic interactions doesn't pose a problem so long as the inclusion of robots increases the team's overall effectiveness. Unfortunately, increasing the supervisor's cognitive load may decrease the team's sustainable performance to the point where robotic agents are more a liability than an asset. Present approaches resolve this problem with adaptive autonomy, where a robot changes its level of autonomy based on the supervisor's cognitive load. This thesis proposes to augment adaptive autonomy by modeling temporal latency and using this model to optimally select the temporal interval between when a supervisor is informed of a pending change and when the robot makes the change. This enables robotic team members to time their actions in response to the supervisor's cognitive load. The hypothesis is confirmed in a user-study where 26 participants interacted with a simulated search-and-rescue scenario.

Relationship functioning in couples has been linked to numerous health outcomes. The purpose of this study was to examine the association between 1) marital functioning and sleep dimensions, 2) marital functioning and cortisol, and 3) sleep dimensions and cortisol. The sample consisted of 108 heterosexual, married couples and was part of a larger marital intervention study. As predicted, poor marital functioning was related to negative sleep outcomes. However, these effects were only significant for wives. There was also evidence to suggest that poor marital functioning was associated with increased cortisol levels in husbands. These effects were independent of age and BMI. Contrary to our hypotheses, cortisol was not linked to sleep outcomes and, therefore, not a mediator of effect between marital functioning and cortisol. However, we did find evidence to suggest that stress and depressive symptomology could mediate the association between dyadic adjustment and sleep. Together, these findings provide evidence for how marital functioning can affect both physical and psychological health.

Irregular applications, such as unstructured mesh operations, do not easily map onto the typical GPU programming paradigms endorsed by GPU manufacturers, which mostly focus on maximizing concurrency for latency hiding. In this work, we show how alternative techniques focused on latency amortization can be used to control overall latency while requiring less concurrency. We used a custom-built microbenchmarking framework to test several GPU kernels and show how the GPU behaves under relevant workloads. We demonstrate that coalescing is not required for efficacious performance; an uncoalesced access pattern can achieve high bandwidth - even over 80% of the theoretical global memory bandwidth in certain circumstances. We also make other further observations on specific relevant behaviors of GPUs. We hope that this study opens the door for further investigation into techniques that can exploit latency amortization when latency hiding does not achieve sufficient performance.

Primary somatosensory cortex (SI) is an important cortical structure involved in receiving and relaying sensory inputs to condition primary motor cortex (M1). The functional interaction between SI and M1 is important for motor control by providing surround inhibition, which is the inhibition of muscles not involved in the movement and in learning new motor skills. This interconnection is known as short-latency afferent inhibition (SAI) and may be probed using Transcranial magnetic stimulation and peripheral nerve stimulation. SAI is dependent on the afferent volley as increasing the nerve stimulation intensity increases the depth of SAI. Individuals with spinal cord injury show reductions in SAI evoked in lower limb and this may be a contributing factor to the impairments in motor control seen within this population. SAI has yet to be investigated in the upper limb in individuals with chronic cervical SCI and this thesis examines these alterations. Two experiments were performed examining M1 excitability (motor evoked potentials), SI excitability (somatosensory evoked potentials) and the interconnection between SI and M1 (SAI). The first Experiment investigated alterations in these measures in individuals with SCI while the second Experiment investigated these measures as a function of the afferent volley. The collective results from Experiment 1 indicate that motor evoked potentials and SAI are reduced but somatosensory evoked potentials are similar to controls. Further data from Experiment 2 indicate that SAI and SEPs increase as a function of the afferent volley and indicate that alterations seen in individuals with SCI may be due to cortical plasticity in the synapses from SI to M1 or within M1. The novel findings of this thesis have indicated aberrant cortical circuits in individuals with SCI and have indicated potential synapses that may be targets for TMS plasticity protocols to alter and restore function to these circuits. / Thesis / Master of Science (MSc)