A comparison of the Shuttle remote manipulator system and the Space Station Freedom mobile servicing center

The Shuttle Remote Manipulator System is a mature system which has successfully completed 18 flights. Its primary functional design driver was the capability to deploy and retrieve payloads from the Orbiter cargo bay. The Space Station Freedom Mobile Servicing Center is still in the requirements definition and early design stage. Its primary function design drivers are the capabilities: to support Space Station construction and assembly tasks; to provide external transportation about the Space Station; to provide handling capabilities for the Orbiter, free flyers, and payloads; to support attached payload servicing in the extravehicular environment; and to perform scheduled and un-scheduled maintenance on the Space Station. The differences between the two systems in the area of geometric configuration, mobility, sensor capabilities, control stations, control algorithms, handling performance, end effector dexterity, and fault tolerance are discussed

Independent writing in grades one and two

Thesis (Ed.M.)--Boston University Page misnomered no 14

Inferring tumour evolution from single-cell and multi-sample data

Tumour development has long been recognised as an evolutionary process during which cells accumulate mutations and evolve into a mix of genetically distinct cell subpopulations. The resulting genetic intra-tumour heterogeneity poses a major challenge to cancer therapy, as it increases the chance of drug resistance. To study tumour evolution in more detail, reliable approaches to infer the life histories of tumours are needed. This dissertation focuses on computational methods for inferring trees of tumour evolution from single-cell and multi-sample sequencing data. Recent advances in single-cell sequencing technologies have promised to reveal tumour heterogeneity at a much higher resolution, but single-cell sequencing data is inherently noisy, making it unsuitable for analysis with classic phylogenetic methods. The first part of the dissertation describes OncoNEM, a novel probabilistic method to infer clonal lineage trees from noisy single nucleotide variants of single cells. Simulation studies are used to validate the method and to compare its performance to that of other methods. Finally, OncoNEM is applied in two case studies. In the second part of the dissertation, a comprehensive collection of existing multi-sample approaches is used to infer the phylogenies of metastatic breast cancers from ten patients. In particular, shallow whole-genome, whole exome and targeted deep sequencing data are analysed. The inference methods comprise copy number and point mutation based approaches, as well as a method that utilises a combination of the two. To improve the copy number based inference, a novel allele-specific multi-sample segmentation algorithm is presented. The results are compared across methods and data types to assess the reliability of the different methods. In summary, this thesis presents substantial methodological advances to understand tumour evolution from genomic profiles of single cells or related bulk samples

Early-Life Socioeconomic Disadvantage and Metabolic Health Disparities.

OBJECTIVE: A quarter of the worlds population have metabolic syndrome (MetS). MetS prevalence is stratified by socioeconomic status (SES), such that low SES is associated with higher MetS risk. The present study examined the relative roles of early-life SES and current SES in explaining MetS risk. METHODS: Participants (N = 354; ages = 15-55 years, M [SD] = 36.5 [10.7] years; 55% female; 72.9% white, 16.9% Asian, 10.2% others) were evaluated for SES and MetS. All were in good health, defined as free of chronic medical illness and acute infectious disease. Using occupational status as a proxy for SES, we recruited roughly equal numbers of participants with low-low, low-high, high-low, and high-high combinations of early-life and current SES. We used the International Diabetes Federation definition for MetS using race- and sex-specific cutoffs for waist circumference, triglyceride levels, high-density lipoprotein cholesterol, blood pressure, and glycosylated hemoglobin levels. RESULTS: Analyses revealed a main effect of low early-life SES on increased MetS risk according to the three separate definitions. They included the traditional MetS diagnosis (odds ratio [OR] = 1.53, confidence interval [CI] = 1.01-2.33, p = .044), the number of MetS components for which diagnostic thresholds were met (OR = 1.61, CI = 1.10-2.38, p = .015), and a continuous indicator of metabolic risk based on factor analysis (F(1,350) = 6.71, p = .010, partial η = .019). There was also a significant interaction of early-life SES and current SES in predicting MetS diagnosis (OR = 1.54, CI = 1.02-2.34). The main effects of current SES were nonsignificant in all analyses. CONCLUSIONS: These findings suggest that MetS health disparities originate in childhood, which may be an opportune period for interventions

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

OncoNEM: inferring tumor evolution from single-cell sequencing data.

Single-cell sequencing promises a high-resolution view of genetic heterogeneity and clonal evolution in cancer. However, methods to infer tumor evolution from single-cell sequencing data lag behind methods developed for bulk-sequencing data. Here, we present OncoNEM, a probabilistic method for inferring intra-tumor evolutionary lineage trees from somatic single nucleotide variants of single cells. OncoNEM identifies homogeneous cellular subpopulations and infers their genotypes as well as a tree describing their evolutionary relationships. In simulation studies, we assess OncoNEM's robustness and benchmark its performance against competing methods. Finally, we show its applicability in case studies of muscle-invasive bladder cancer and essential thrombocythemia.The authors would like to acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. This work was funded by CRUK core grant C14303/A17197.This is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s13059-016-0929-

Heat stress adaptations in pigs

Implications • Heat stress is a global issue constraining animal agriculture productivity, negatively affects welfare, and reduces production efficiency in many countries. • The effects of heat stress on pig production will intensify, if climate change continues as predicted. • To date, modifying the environment is the most effective way to mitigate the effects of heat stress. • Identifying additional strategies (nutritional and genetics) to maximize pork production during the warm summer months is necessary to satiate a growing demand for high quality meat for human consumption

Regulators of genetic risk of breast cancer identified by integrative network analysis.

Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.This work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

Production of monodisperse large drop emulsions by means of high internal phase pickering emulsions ─ processing and formulation

ABSTRACT: High internal phase Pickering emulsions (HIPPE) have received significant research attention in the last two decades due to their potential for a wide range of applications. The appropriate processing of such high-viscosity emulsions, hundreds of times more viscous than that of the continuous phase, and the control of the final droplet size remain challenges to be tackled. Our research targeted this knowledge gap by examining the influence of the emulsion formulation and the processing conditions on the final droplet size. The dispersed phase fraction (100 cSt silicon oil) ranged between 75 and 80%. The emulsions were produced in a regular mixing tank equipped with a helical ribbon impeller rotating at a low speed (100–150 rpm). The effective viscosity of the continuous phase was obtained from the experimental torque measurements. The droplet size distributions were measured after emulsification and dilution in the continuous phases. It is shown that the capillary number obtained from the observed emulsification performance can help predict the final droplet size. Our approach provides a straightforward methodology to generate concentrated Pickering emulsions with controlled and predictable droplet size