BACKGROUND: Sleep problems affect people of all ages, race, gender, and socioeconomic classifications. Undiagnosed sleep disorders significantly and adversely impact a person’s level of academic achievement, job performance, and subsequently, socioeconomic status. Undiagnosed sleep disorders also negatively impact both direct and indirect costs for employers, the national government, and the general public. Sleepiness has significant implications on quality of life by impacting occupational performance, driving ability, cognition, memory, and overall health. The purpose of this study is to describe the prevalence of daytime sleepiness, as well as other quantitative predictors of sleep continuity and quality. METHODS: Population data from the CDC program in fatigue surveillance were used for this secondary analysis seeking to characterize sleep quality and continuity variables. Each participant underwent a standard nocturnal polysomnography and a standard multiple sleep latency test (MSLT) on the subsequent day. Frequency and chi-square tests were used to describe the sample. One-Way Analysis of Variance (ANOVA) was used to compare sleep related variables of groups with sleep latencies of <5 >minutes, 5-10 minutes, and >10 minutes. Bivariate and multivariate logistic regression was used to examine the association of the sleep variables with sleep latency time. RESULTS: The mean (SD) sleep latency of the sample was 8.8 (4.9) minutes. Twenty-four individuals had ≥1 SOREM, and approximately 50% of participants (n = 100) met clinical criteria for a sleep disorder. Individuals with shorter sleep latencies, compared to those with longer latencies reported higher levels of subjective sleepiness, had higher sleep efficiency percentages, and longer sleep times. The Epworth Sleepiness Scale, sleep efficiency percentage, total sleep time, the presence of a sleep disorder, and limb movement index were positively associated with a mean sleep latency of <5 >minutes. CONCLUSIONS: The presence of a significant percentage of sleep disorders within our study sample validate prior suggestions that such disorders remain unrecognized, undiagnosed, and untreated. In addition, our findings confirm questionnaire-based surveys that suggest a significant number of the population is excessively sleepy, or hypersomnolent. Therefore, the high prevalence of sleep disorders and the negative public health effects of daytime sleepiness demand attention. Further studies are now required to better quantify levels daytime sleepiness, within a population based sample, to better understand their impact upon morbidity and mortality. This will not only expand on our current understanding of daytime sleepiness, but it will also raise awareness surrounding its significance and relation to public health.

Equine Herpesvirus type 1 (EHV-1) is a worldwide threat to the health of horses. It can cause mild respiratory disease, abortions and deaths of newborn foals as well as a potentially fatal neurologic disorder known as Equine Herpesvirus Myeloencephalopathy (EHM). The virus is maintained in populations by stress-induced periodic reactivation of virus in long-term latently infected horses and transmission of the reactivated virus to susceptible individuals. In horses, peripheral blood leukocytes (PBLs) are thought to be an important site for EHV-1 latent genomes. Since the Unfolded Protein Response (UPR) is a cellular response to a variety of stressors that has been linked to reactivation of herpes simplex virus in humans, a virus closely related to EHV-1, I tested the hypothesis that latent EHV-1 relies on the UPR as a pluripotent stress sensor and uses it to reactivate lytic gene expression. Since little work has been done in defining the UPR in horses, I first successfully developed a quantitative real-time polymerase chain reaction (RT-qPCR) assay to detect and quantitate transcripts for selected UPR genes in equine dermal (E.Derm) cells and PBLs. Activation of the UPR was achieved in both cell types using thapsigargin and a difference in gene expression after activation of the UPR in two equine cell types was found. A nested PCR assay to detect and distinguish latent EHV-1 and EHV-4 was evaluated and the sensitivity of the technique to detect EHV-1 was determined. I discovered that the nested PCR technique was not sensitive enough to detect the estimated one latent viral genome in 50,000 PBLs. Lytic EHV-1 infection was characterized by single step growth curve in E.Derm cells and consistent detection of temporal EHV-1 gene expression by RT-qPCR was achieved. The relationship between EHV-1 gene expression and UPR gene expression during lytic infection was investigated. While EHV-1 infection had no effect on UPR gene expression, activation of the UPR appeared to decrease the expression of EHV-1 genes temporarily and reversibly during the first 4 h after infection. Finally, detection of EHV-1 in PBLs from horses presumed to be latently infected by co-cultivation with E. Derm cells permissive to EHV-1 infection was attempted. To detect viral DNA, PBLs were stimulated with thapsigargin or interleukin 2 (IL-2) which was previously reported to induce reactivation of latent EHV-1. I was not able to reproduce previously published experiments of reactivation in vitro of latent EHV-1 by stimulation with IL-2, and virus reactivation did not occur after stimulation of PBLs with thapsigargin. In summary, a RT-qPCR assay to measure the expression of equine UPR genes was developed and activation of the UPR by treatment of E.Derm cells and PBLs with thapsigargin was successfully achieved. A difference in gene expression after activation of the UPR in two equine cell types was found. In contrast to what has been reported for other alphaherpesviruses, there appears to be no, or only little, interaction between the UPR and EHV-1 during viral infection. Detection of latent EHV-1 genomes in PBLs was not achieved by using a nested PCR, as this technique was not sensitive enough to detect the estimated one latent viral genome in 50,000 PBLs. Finally, latent EHV-1 was not detected in presumed latently infected PBLs or reactivated by triggering the UPR in equine PBLs.

This thesis work investigates the effects of crosstalk on on-chip interconnects. We use optimal repeater insertion as a reference and derive analytical expressions for signal latency, maximum data-rate and power consumption. Through calculations and simulations we show that despite large uncertainties in arrival time of a signal that is subject to crosstalk, we are able to make predictions about the maximum data-rate on a bus. We also show that data-rates can exceed the classical limit of the latency inverted by using wave pipelining. To increase the data-rate, we can increase the number of repeaters to a limit, at the cost of additional latency and power. Savings in power consumption can be achieved by using fewer repeaters, paying in latency and data-rate. Through fewer repeaters, the top metal layer shows better performance in all investigated aspects.

The human gammaherpesviruses EBV and KSHV realize their oncogenic potential during latent infection. The species specificity of the human gammaherpesviruses has hindered the study of latency in animal models. Murine gammaherpesvirus MHV-68 (MHV-68) may be used as a representative gammaherpesvirus for the study of latency. The goal was to establish an in vitro model of MHV-68 latency using replication defective MHV-68. ORF50 has been identified as the major viral trans-activator essential for entry into the lytic replication cycle and necessary and sufficient for reactivation of MHV-68 virus from latency. ORF50 null mutants (A50) can theoretically be used to infect cells in vitro to facilitate an analysis of virus gene expression and episome maintenance during latency. In this project A50 mutants containing the luciferase or green fluorescence protein (GFP) under OW50 promoter control were used to infect a variety of cell types. 3T3 fibroblasts are a permissive cell line and were used for an initial characterization of the ability of A50 MHV-68 to establish latency. B lymphocytes and macrophages are the major reservoirs of persistence in vivo thus the ability of A50 mutants to establish latency in NSO B and RAW macrophage cell lines was explored. Latency was readily established and maintained in 3T3 and RAW cells. The low infectability of NSO B- cells restricted the utility of this cell line in studies of latency. Examination of patterns of lytic and latent transcription in 3T3 and RAW cells coordinately infected with A50 MHV-68 revealed reactivation efficiencies of 40-60%. Following long-term passage A50 exhibited stable transcription of two latency related genes M2 and ORF73, with episomal maintenance of the viral genome, in the absence of contaminating lytic infection. The results demonstrate the utility of A50 mutants for studies of gammaherpesvirus latency in vivo.

Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 89-103). Also available on the Internet.

Functional Analysis is a widely used and effective tool for the assessment of challenging behavior. However, there are several practical issues associated with analogue functional analysis, including the reinforcement of challenging behavior and the extended duration of the assessment process. These issues have been addressed in several modified functional analysis models, including the brief functional analysis. The brief functional analysis allows practitioners and researchers to complete an assessment of challenging behavior within a 90-minute period, thus addressing the practical issue of extended duration. It does not, however, address the potential issues associated with the reinforcement of challenging behavior. The current study evaluated the efficacy of three modified functional analysis methods, including a brief antecedent-based analysis (A-B), a brief latency-based analysis, and a brief functional analysis (A-B-C). Results from each assessment were compared and high levels of correspondence was observed between the respective assessment models. Results are discusses in terms of the relative strengths and limitations of each of the models. / text

The purpose of this dissertation was to compare two methods of assessing challenging behavior in young children in the home setting and to determine if the two methods could result in the same outcome. Results indicated that there was full correspondence between the two assessment methods for three out of five participants, and among 19 comparisons, 16 agreements were made (84%). Future research should validate latency functional analysis via treatment evaluation with this population. / text

Networking research and development have historically focused on increasing network throughput and path resource utilization, which particularly helped bulk applications such as file transfer and video streaming. Recent over-provisioning in the core of the Internet has facilitated the use of interactive applications like interactive web browsing, audio/video conferencing, multi- player online gaming and financial trading applications. Although the bulk applications rely on transferring data as fast as the network permits, interactive applications consume rather little bandwidth, depending instead on low latency. Recently, there has been an increasing concern in reducing latency in networking research, as the responsiveness of interactive applications directly influences the quality of experience. To appreciate the significance of latency-sensitive applications for today's Internet, we need to understand their traffic pattern and quantify their prevalence. In this thesis, we quantify the proportion of potentially latency-sensitive traffic and its development over time. Next, we show that the flow start-up mechanism in the Internet is a major source of latency for a growing proportion of traffic, as network links get faster. The loss recovery mechanism in the transport protocol is another major source of latency. To improve the performance of latency-sensitive applications, we propose and evaluate several modifications in TCP. We also investigate the possibility of prioritization at the transport layer to improve the loss recovery. The idea is to trade reliability for timeliness. We particularly examine the applicability of PR-SCTP with a focus on event logging. In our evaluation, the performance of PR-SCTP is largely influenced by small messages. We analyze the inefficiency in detail and propose several solutions. We particularly implement and evaluate one solution that utilizes the Non-Renegable Selective Acknowledgments (NR-SACKs) mechanism, which has been proposed for standardization in the IETF. According to the results, PR-SCTP with NR-SCAKs significantly improves the application performance in terms of low latency as compared to SCTP and TCP. / Interactive applications such as web browsing, audio/video conferencing, multi-player online gaming and financial trading applications do not benefit (much) from more bandwidth. Instead, they depend on low latency. Latency is a key determinant of user experience. An increasing concern for reducing latency is therefore currently being observed among the networking research community and industry. In this thesis, we quantify the proportion of potentially latency-sensitive traffic and its development over time. Next, we show that the flow start-up mechanism in the Internet is a major source of latency for a growing proportion of traffic, as network links get faster. The loss recovery mechanism in the transport protocol is another major source of latency. To improve the performance of latency-sensitive applications, we propose and evaluate several modifications in TCP. We also investigate the possibility of prioritization at the transport layer to improve the loss recovery. The idea is to trade reliability for timeliness. We particularly examine the applicability of PR-SCTP with a focus on event logging. In our evaluation, the performance of PR-SCTP is largely influenced by small messages. We analyze the inefficiency in detail and propose several solutions. We particularly implement and evaluate one solution that utilizes the Non-Renegable Selective Acknowledgments (NR-SACKs) mechanism, which has been proposed for standardization in the IETF. According to the results, PR-SCTP with NR-SCAKs significantly improves the application performance in terms of low latency as compared to SCTP and TCP.

The aggressive scaling of the semiconductor technology following the Moore’s Law has delivered true system-on-chip (SoC) integration. Network-on-chip (NoC) has been recently introduced as an effective solution for scalable on-chip communication since dedicated point-to-point (P2P) interconnection and shared bus architecture become performance and power bottlenecks in the SoCs. This dissertation studies three critical NoC challenges such as latency, power, and compatibility with emerging technologies in aspect of an architecture and physical design level. Latency is a key issue in NoC since the performance of applications considerably depends on resource sharing policies employed in an on-chip network. NoCs have been mainly developed to improve network-level performance that captures the inherent performance characteristics of a network itself, but the network-level optimizations are not directly related to application- or system-level performance. In addition, memory latency on NoC critically affects the performance of applications or systems. We propose a synchronous dynamic random access memory (SDRAM) aware NoC design to optimize memory throughput, latency, and design complexity. Furthermore, it is extended to an application-aware NoC design to provide the quality-of-service (QoS) of memory for various applications. NoC provides great on-chip communication. However, it brings no true relief to power budget when the on-chip network scales in terms of complexity/size and signal bandwidth. The combination of NoC and other techniques has the potential to reduce power. We study two power saving research topics for NoC: (a) we propose a voltage-frequency island (VFI) aware NoC optimization framework with a better tradeoff between power efficiency and design complexity to minimize both computation and on-chip communication power. (b) We formulate an application mapping problem to mixed integer quadratic programming (MIQP) with the purpose of reducing power consumption in various hard networks and develop highly efficient algorithms for the MIQP. Regarding NoC compatible with new technologies, we focus on three dimensional (3D) die integration based on through-silicon vias (TSVs). Since an on-chip network design has been subject to not only application constraints but also design/manufacturing constraints, a 3D NoC design is required for innovation in interconnection networks. We propose a chemical-mechanical polishing (CMP) aware application-specific 3D NoC design that minimizes TSV height variation, thus reduces bonding failure, and meanwhile optimizes conventional NoC design objectives such as hop count, wirelength, power, and area. / text

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