Acceptance Testing and Energy-based Mission Reliability in Unmanned Ground Vehicles.

The objective of this research is to explore and develop new methodologies and techniques to improve UGV mission reliability. This dissertation focuses on two research issues that are critical in the following UGV deployment phases: (1) prior to field deployment to remove design deficiencies; and (2) during field usage to prevent mission failures. Four specific research topics are accomplished. The first topic focuses on simulation-based acceptance testing. A general framework is proposed to integrate dynamic and static simulations. Statistical hypothesis testing is used to compare static and dynamic simulations to determine when a simple static simulation can be used to replace the complex dynamic simulation. Results show that the static simulation can be used when a failure mechanism is not significantly affected by the dynamic characteristics of the vehicle. The remaining research topics aim at prevention of operational failures due to unexpected energy depletion. A model-based Bayesian prediction framework integrated with a dynamic vehicle model is proposed in the second research topic, which improves traditional approaches for estimation and prediction. The Bayesian framework combines mission prior knowledge with real-time measurements for adaptive prediction of end-of-mission energy requirement. Experimental studies were conducted, which validated and demonstrated the advantages of the framework on roads with different surface types and grades. The third research topic, entitled real-time energy reliable path planning, builds upon the above mentioned prediction framework to identify the most energy reliable path in a stochastic network with unknown and correlated arc lengths. Since traditional sequential optimization techniques cannot be directly applied to this problem, a heuristic approach based on two stage exploration/exploitation is proposed to identify the most reliable path. The framework, which minimizes the cost of exploration, outperforms traditional path planning approaches. In the final research topic, the impact of operator driving style on mission energy requirements is investigated using statistical response surface. While the previous topics help with overall mission planning regardless of the operator’s driving style, here, improving the driving style to increase energy availability is studied. The optimal drive cycle that minimizes energy consumption and procedures for reduction of energy consumption are proposed.PhDIndustrial & Operations EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107075/1/sadrpour_1.pd

Epidemiology of Chlamydia trachomatis in the Middle East and north Africa: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The epidemiology of Chlamydia trachomatis in the Middle East and north Africa is poorly understood. We aimed to provide a comprehensive epidemiological assessment of C trachomatis infection in the Middle East and north Africa. METHODS: We did a systematic review of C trachomatis infection as well as a meta-analysis and meta-regression of C trachomatis prevalence. We searched PubMed and Embase, as well as regional and national databases up to March 13, 2019, using broad search terms with no language or year restrictions. Any document or report including biological measures for C trachomatis prevalence or incidence was eligible for inclusion. We extracted all measures of current (genital or rectal), recent, and ever infection with C trachomatis. We estimated pooled average prevalence in different populations using random-effects meta-analysis. Factors associated with prevalence and sources of between-study heterogeneity were determined using meta-regression. FINDINGS: We identified a total of 1531 citations, of which 255 reports contributed to 552 C trachomatis prevalence measures from 20 countries. No incidence measures were identified. Pooled prevalence of current genital infection was 3·0% (95% CI 2·3-3·8) in general populations, 2·8% (1·0-5·2) in intermediate-risk populations, 13·2% (7·2-20·7) in female sex workers, 11·3% (9·0-13·7) in infertility clinic attendees, 12·4% (7·9-17·7) in women with miscarriage, 12·4% (9·4-15·7) in symptomatic women, and 17·4% (12·5-22·8) in symptomatic men. Pooled prevalence of current rectal infection was 7·7% (4·2-12·0) in men who have sex with men. Substantial between-study heterogeneity was found. Multivariable meta-regression explained 29·0% of variation. Population type was most strongly associated with prevalence. Additional associations were found with assay type, sample size, country, and sex, but not with sampling methodology or response rate (about 90% of studies used convenience sampling and >75% had unclear response rate). There was no evidence for temporal variation in prevalence between 1982 and 2018. INTERPRETATION: C trachomatis prevalence in the Middle East and north Africa is similar to other regions, but higher than expected given its sexually conservative norms. High prevalence in infertility clinic attendees and in women with miscarriage suggests a potential role for C trachomatis in poor reproductive health outcomes in this region. FUNDING: National Priorities Research Program from the Qatar National Research Fund (a member of Qatar Foundation)

The Role of PI4KB in Cellular Localization of Small GTPases

Constitutively active oncogenic mutant K-Ras is one the principal contributors to human cancers including 90% of pancreatic, 50% of colorectal and 32% of non-small cell lung cancers. However, except for K-Ras G12C oncogenic mutant, which only presents in about 13% of non-small cell lung cancer patients, there is no anti-K-Ras therapy for a considerable subset of K-Ras mutations in human tumors, reflecting challenges for targeting oncogenic K-Ras activity. K-Ras is a membrane-bound small GTPase; when active, it triggers multiple signaling pathways regulating a variety of key cellular functions such as cell growth, proliferation and survival. To initiate these signaling cascades, K-Ras must localize to the plasma membrane (PM), where gets activated by guanine-nucleotide exchange factors and interact with its downstream effectors. Based on this dependency of K-Ras localization to the PM for its biological activity, removing K-Ras from the PM has been suggested as an anti-K-Ras approach. The exact mechanism of K-Ras interaction with the PM is not fully elucidated. Extensive studies have shown a specific preference of K-Ras for interacting with phosphatidylserine (PS), an acidic phospholipid in the inner PM leaflet, and decrease in the PS contents dissociates K-Ras from the PM and blocks K-Ras signaling. Towards our goal of targeting the PM/K-Ras interaction, our recent study has indicated that phosphatidylinositol 4-kinase IIIβ (PI4KB), which converts PI to PI 4-phosphate at the Golgi complex, is involved in the PM enrichment of PS and K-Ras. We found that upon PI4KB inhibition, K-Ras and PS redistribute from the PM to mitochondria and other endomembranes, respectively. The aims of this dissertation are to 1) characterize PI4KB as an anti-K-Ras target in human pancreatic cancer cell lines expressing oncogenic mutant K-Ras, and 2) assess the mechanism of K-Ras translocation to mitochondria upon PI4KB inhibition. Our proliferation assay data demonstrate that chemical inhibitors for PI4KB reduced the growth of human pancreatic cancer cells harboring oncogenic mutant K-Ras, but not wild-type K-Ras. These data suggest that PI4KB could be a target for treating human pancreatic cancers. In the second aim of study, we sought to elucidate whether the polybasic domain (PBD) of K-Ras is involved in mitochondrial translocation of K-Ras in PI4KB inhibited cells. K-Ras is distinct from the other Ras isoforms, H-Ras and N-Ras, for its PM targeting signal. While H- and N-Ras bind the PM via the C-terminal prenyl and palmitoyl lipid moieties, K-Ras binds the PM through the C-terminal prenyl lipid moiety and PBD made of hexa-Lys residues. Also, the PBD electrostatically interacts with the PM PS, and depleting PM PS content dissociates K-Ras from the PM. Our data show that PI4KB inhibition translocates K-Ras, but not H -Ras, to mitochondria. Thus, we propose that K-Ras PBD is involved in translocation to mitochondria upon PI4KB inhibition. To test this, we examined the mitochondrial localization of four small GTPases containing PBD in PI4KB-inhibited cells: Rac1, RalA, Arl4a and Arl4c. Our data demonstrate that PI4KB inhibition promotes mitochondrial translocation of RalA, which has a closer sequence and structure to K-Ras compared to the other three small GTPase, even though K-Ras and RalA use different prenyl groups for the PM anchoring. Taken together, here we identified PI4KB as a possible therapeutic candidate for treating human pancreatic cancers harboring oncogenic mutant K-Ras. Moreover, different observations made for the effect of PI4KB inhibition on the localization of four small GTPases containing PBD indicate that PBD-mediated PM anchoring is not a deceptively simple electrostatic interaction, which only is based on positive charges provided by PBD. Although further studies are needed to explore the exact mechanism of this interaction, we propose that in addition to positive charges, primary sequences of PBD, and intramolecular interactions (non-covalent bonds) also play roles. Moreover, it is feasible to consider the possibility that the membrane localization of small GTPase is also regulated by their effector proteins, where they recruit to and/or stabilize the membrane localization of small GTPases

Detection of Chlamydia trachomatis and Mycoplasma genitalium in semen samples of infertile men using multiplex PCR

Background: Chlamydia trachomatis is the most common bacterial sexually transmitted infection in the world, but the effect of this infection on male fertility is still controversial. Despite reports of interaction between Mycoplasma genitalium and sperm, this pathogen in semen samples of infertile men is less studied. We studied, the prevalence of Chlamydia trachomatis and Mycoplasma genitalium infection in infertile men.Methods: Among attending Avicenna Infertility Center, 120 men who had abnormal semen analysis tests were selected and the samples were taken. After detailed analysis of semen quality, DNA was extracted from each sample by chelex. Samples were evaluated for these two pathogens by multiplex PCR. Results were statistically analyzed.Results: Chlamydia trachomatis and Mycoplasma genitalium was detected in 23/3% and 12/5% of the samples, respectively. Although, Mycoplasma genitalium infection rises by increasing (P=0.640) and decreasing in age of first sexually activity (P=0.203), and also positive cases of Chlamydia trachomatis infection showed increase regarding age increase (P=0.619) and age decrease in first sexually activity (P=0.511), but these differences were not statistically significant. Conclusion: All in all, regarding to the increased prevalence of Chlamydia trachomatis infection compared with the only similar study in Iran and high prevalence of Mycoplasma genitalium infection in infertile men, this assessment was done. A multiplex PCR protocol rapidly and simultaneously identify these organisms in comparison with uniplex from clinical samples. Based on our results screening for Chlamydia trachomatis and Mycoplasma genitalium infection among infertile men seems to be valuable

Evaluation of Alternative Estrogen Activity Assays for New Computational Models to Support the Endocrine Disruption Screening Program

Poster presented to SOT Conference 2024: A New Approach Method (NAM) to Screen for the Impact of Endogenous Stress on Chemical Toxicity Search for CCTE records in EPA’s Science Inventory by typing in the title at this link.https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25</p

An economic evaluation of adaptation pathways in coastal mega cities: An illustration for Los Angeles

Sea level rise and uncertainty in its projections pose a major challenge to flood risk management and adaptation investments in coastal mega cities. This study presents a comparative economic evaluation method for flood adaptation measures, which couples a cost–benefit analysis with the concept of adaptation pathways. Our approach accounts for uncertainty in sea level rise projections by allowing for flexibility of adaptation strategies over time. Our method is illustrated for Los Angeles County which is vulnerable to flooding and sea level rise. Results for different sea level rise scenarios show that applying adaptation pathways can result in higher economic efficiency (up to 10%)than individual adaptation strategies, despite the loss of efficiency at the initial strategy. However, we identified ‘investment tipping points’, after which a transition could decrease the economic efficiencies of a pathway significantly. Overall, we recommend that studies evaluating adaptation strategies should integrate cost–benefit analysis frameworks with adaptation pathways since this allows for better informing decision makers about the robustness and economic desirability of their investment choices

Assessment of the Effects of a Novel Herbal Immunomodulator Drug (IMOD) on Cytokine Profiles in Experimental Canine Visceral Leishmaniasis: a Preliminary Survey

Background: Cytokines play a fundamental role in the regulation of immune responses in remission and/or relapsing of leishmaniasis. Therefore, immunotherapy for the treatment of canine visceral leishmaniasis (CVL) has represented a principle approach in control of the infection. The present research aimed to evaluating the immunotherapeutic potential of a novel herbal immunomodulator drug (IMOD) on CVL. Methods: Twelve mongrel dogs were intravenously infected with Iranian strain of L. infantum and randomly divided into three groups; 1: negative control (non-infected), 2: immunotherapy with IMOD and 3: positive control (non-treated). Cell proliferation and Th1-/Th2-type cytokines were measured in peripheral blood mononuclear cell (PBMC) by cell proliferation kit I (MTT) and enzyme-linked immunospot (ELISpot) assays, respectively. Results : At the 60 days follow-up assessment, no adverse effects were observed in treated interventional group. Cellular proliferation assay indicated that PBMCs of IMOD group had higher stimulation index (SI) than positive control group (p <0.05). Enhancement of CD4+ T cells such as IL-2, IL-4 & IL-10 were detected in negative control group due to in vitro IMOD stimulation 30 days post-treatment. In accordance to decreasing trends of Th1 & Th2 cytokines in positive control group, the mean number of IFN-γ, IL-2, IL-4 and IL-10 spot forming cells (SFCs) down regulated for IMOD group during the study. Conclusion: These data indicate that IMOD had immunomodulatory potential but is not sufficient for total parasitic cure due to balance of Th1/Th2 cytokines. This is a preliminary study and we propose to undertake a series of experiments to evaluate the CVL due to in vitro modulatory effects of IMOD

Pathways to resilience: Adapting to sea level rise in Los Angeles

Los Angeles (LA) County's coastal areas are highly valued for their natural benefits and their economic contributions to the region. While LA County already has a high level of exposure to flooding (e.g. people, ports, and harbors), climate change and sea level rise will increase flood risk; anticipating this risk requires adaptation planning to mitigate social, economic, and physical damage. This study provides an overview of the potential effects of sea level rise on coastal LA County and describes adaptation pathways and estimates associated costs in order to cope with sea level rise. An adaptation pathway in this study is defined as the collection of measures (e.g., beach nourishment, dune restoration, flood‐proofing buildings, and levees) required to lower flood risk. The aim of using different adaptation pathways is to enable a transition from one methodology to another over time. These pathways address uncertainty in future projections, allowing for flexibility among policies and potentially spreading the costs over time. Maintaining beaches, dunes, and their natural dynamics is the foundation of each of the three adaptation pathways, which address the importance of beaches for recreation, environmental value, and flood protection. In some scenarios, owing to high projections of sea level rise, additional technical engineering options such as levees and sluices may be needed to reduce flood risk. The research suggests three adaptation pathways, anticipating a +1 ft (0.3 m) to +7 ft (+2 m) sea level rise by year 2100. Total adaptation costs vary between $4.3 and$6.4 bn, depending on measures included in the adaptation pathway