Investigation of the interaction between Ebola virus and the host

Ebola viruses cause viral haemorrhagic fever in humans and non human primates. Due to the severity of their symptoms, the lack of an approved treatment or vaccine, and the mechanism of transmission, these viruses have been classified as containment level 4 (CL4) pathogens. In December 2013, an Ebola virus outbreak initiated in West Africa, which lasted more than two years, and has been considered the worst outbreak in the history of the Ebola viruses. More than twenty-seven thousand people had a positive diagnosis of infection with more than eleven thousand confirmed dead. This outbreak highlights not only the urgent necessity for new treatments and vaccines against this virus but also that there is still a large knowledge gap for Ebola viruses compared to other pathogens. This thesis focuses on using high resolution approaches to characterise the interaction between the Zaire ebolavirus species (EBOV) and the host. The work focuses on using high resolution sequencing to characterise the evolution of EBOV throughout the outbreak in West Africa and also in adapting to grow in a novel host. The work also focuses on two viral proteins that are critical to the virus life cycle. The VP24 protein that is an interferon antagonist and the nucleoprotein (NP) which encapsidates the viral genome. Quantitative proteomics was used to identify host cell proteins that interacted with these viral proteins and inhibitors were used to ablate cellular protein function and monitor the effect on viral biology. The thesis is written in the style of ‘by publication’ and the publications associated with this work are reproduced in the Appendix

B 0 field inhomogeneity considerations in pseudo‐continuous arterial spin labeling (pCASL): effects on tagging efficiency and correction strategy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89456/1/nbm1675.pd

Supersymmetry versus precision experiments revisited

We study constraints on the Minimal Supersymmetric Standard Model from electroweak experiments. We find that the light sfermions always make the fit worse than the Standard Model, while the light chargino generally make the fit slightly better through the oblique corrections. The best overall fit to the precision measurements are found when the mass of lighter chargino is about 100 GeV and the SU(2)_L doublet sfermions are all much heavier. We find the slight improvement of the fit over the SM, where the total \chi^2 of the fit decreases by about one unit.Comment: 3 pages, 2 figures, LaTeX2e, used ws-p10x7.cls (included), talk given at ICHEP2000, Osaka, Japa

Are Portable Imaging Intraoperative Radiographs Helpful for Assessing Adequate Acetabular Cup Positioning in Total Hip Arthroplasty?

Despite advances in surgical techniques and instrumentation, current intra-operative estimations of acetabular version in total hip arthroplasty are of limited accuracy. In the present study, two experienced orthopedic surgeons compared intra-operatively measured (using portable imaging) anteversions and vertical inclinations of acetabular components with those measured using standardized radiographs post-operatively in 40 patients. Of the all vertical inclinations measured from intra-operative radiographs, 72.5% (n=29) were within ±2°, and 97.5% (n=39) were within ±5° of those determined using post-operative radiographs, and for anteversion, 52.5% (n=21) were within ±2°, and 97.5% (n=39) were within ±5°. Post-operative radiographs demonstrated that 90.0% (n=36) of vertical inclinations and anteversions were within the adequate zone. Obviously, our method has its limitations, but the authors conclude that the method described in this article better allows surgeons to verify acetabular version intra-operatively. In particular, the described method is suitable in cases with a deformed acetabular anatomy and difficult revision surgery

Simulation model generation combining IFC and CityGML data

The energy efficiency requirements at district scale revealed the need for detailed building energy simulations, with which the overall district energy demand can be estimated with an acceptable degree of accuracy. In order to meet this need, an automated simulation model generation process is introduced at the context of the European project OptEEmAL, which includes: a query stage where data are gathered from IFC, CityGML files, and a transformation stage where a single IDF file is generated for a building in a district environment, suitable for EnergyPlus simulations. The queried data are assumed to conform to certain correctness, completeness and consistency conditions across district and building scales. As a demonstration example, a simulation model is generated for a specific building. Future improvements of this work are discussed related to the integration of all the data requirements of the proposed process, in a District Data Model under an ontological framework

Birth Outcomes of Koreans by Birthplace of Infants and Their Mothers, the United States versus Korea, 1995-2004

The acculturation effect of immigrant women on birth outcomes varies by race. We examined birth outcomes of three groups of births for the period 1995-2004, USA births to the USA-born Korean mothers, USA births to the non-USA-born Korean mothers, and births in Korea. In singleton USA births to both Korean parents, average birth weight was 3,294 g for the USA-born Korean mothers and 3,323 g for the non-USA-born Korean mothers. However, this difference was not significant, once controlled for other maternal sociodemographic, obstetric and medical factors. Low birth weight and prematurity prevalence were not different by maternal nativity between these two singleton groups. Average birth weight of all births including multiplets in Korea was 3,270 g, compared to 3,297 g for all USA-born infants including multiplets and births either to both or one Korean parents. This difference might have reflected a significantly lower educational attainment of mothers in Korea compared to Korean mothers in the USA. Low birth weight rate was consistently lower in infants born in Korea compared to the USA-born, but this difference became less, 4.2% and 4.6% respectively by 2004. These observations suggest that in the USA acculturation effect of Korean immigrants on birth outcomes is negligible

Klhl31 attenuates β-catenin dependent Wnt signaling and regulates embryo myogenesis

Klhl31 is a member of the Kelch-like family in vertebrates, which are characterized by an amino-terminal broad complex tram-track, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domain, carboxy-terminal Kelch repeats and a central linker region (Back domain). In developing somites Klhl31 is highly expressed in the myotome downstream of myogenic regulators (MRF), and it remains expressed in differentiated skeletal muscle. In vivo gain- and loss-of-function approaches in chick embryos reveal a role of Klhl31 in skeletal myogenesis. Targeted mis-expression of Klhl31 led to a reduced size of dermomyotome and myotome as indicated by detection of relevant myogenic markers, Pax3, Myf5, myogenin and myosin heavy chain (MF20). The knock-down of Klhl31 in developing somites, using antisense morpholinos (MO), led to an expansion of Pax3, Myf5, MyoD and myogenin expression domains and an increase in the number of mitotic cells in the dermomyotome and myotome. The mechanism underlying this phenotype was examined using complementary approaches, which show that Klhl31 interferes with β-catenin dependent Wnt signaling. Klhl31 reduced the Wnt-mediated activation of a luciferase reporter in cultured cells. Furthermore, Klhl31 attenuated secondary axis formation in Xenopus embryos in response to Wnt1 or β-catenin. Klhl31 mis-expression in the developing neural tube affected its dorso-ventral patterning and led to reduced dermomyotome and myotome size. Co-transfection of a Wnt3a expression vector with Klhl31 in somites or in the neural tube rescued the phenotype and restored the size of dermomyotome and myotome. Thus, Klhl31 is a novel modulator of canonical Wnt signaling, important for vertebrate myogenesis. We propose that Klhl31 acts in the myotome to support cell cycle withdrawal and differentiation

Endothelin A Receptor Blockade Influences Apoptosis and Cellular Proliferation in the Developing Rat Kidney

Endothelin systems are believed to play important roles in the emergence and maintenance of functions of various organs during perinatal development, including the kidney. The present study was designed to investigate the roles of endothelin systems on physiologic renal growth and development. Newborn rat pups were treated with either Bristol-Myers Squibb-182874 (30 mg/kg/day), a selective endothelin A receptor (ETAR) antagonist, or vehicle for 7 days. To identify cellular changes, kidneys were examined for apoptotic cells by terminal deoxynucleotide transferase-mediated nick-end labeling stain and proliferating cell nuclear antigen (PCNA) by immunohistochemical (IHC) stain. To clarify the molecular control of these processes, immunoblots and reverse transcriptase-polymerase chain reaction for Clusterin, Bcl-2, Bcl-XL, Bax, and p53 were performed. ETAR antagonist treatment resulted in reduced kidney weights, decreased PCNA-positive proliferating cells, and increased apoptotic cells. The protein expressions of renal Bcl-XL and Bax in the ETAR antagonist-treated group were significantly decreased, whereas the mRNA expressions of these genes were not changed. There were no significant differences in the expressions of Clusterin, Bcl-2, and p53. In conclusion, inhibition of endogenous endothelins impairs renal growth, in which decreased cellular proliferation, increased apoptosis and decreased expressions of renal Bcl-XL and Bax are possibly implicated

Development of a 2-Channel Embedded Infrared Fiber-Optic Temperature Sensor Using Silver Halide Optical Fibers

A 2-channel embedded infrared fiber-optic temperature sensor was fabricated using two identical silver halide optical fibers for accurate thermometry without complicated calibration processes. In this study, we measured the output voltages of signal and reference probes according to temperature variation over a temperature range from 25 to 225 °C. To decide the temperature of the water, the difference between the amounts of infrared radiation emitted from the two temperature sensing probes was measured. The response time and the reproducibility of the fiber-optic temperature sensor were also obtained. Thermometry with the proposed sensor is immune to changes if parameters such as offset voltage, ambient temperature, and emissivity of any warm object. In particular, the temperature sensing probe with silver halide optical fibers can withstand a high temperature/pressure and water-chemistry environment. It is expected that the proposed sensor can be further developed to accurately monitor temperature in harsh environments