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

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

Optimally graded porous material for broadband perfect absorption of sound

International audienceThis article presents a numerical optimization procedure of continuous gradient porous layer properties to achieve perfect absorption under normal incidence. This design tool is applied on a graded porous medium composed of a periodic arrangement of ordered unit cells allowing to link the effective acoustic properties to its geometry. The best micro-geometry continuous gradient providing the optimal acoustic reflection and/or transmission is designed via a nonlinear conjugate gradient algorithm. The acoustic performances of the so-designed continuous graded material are discussed with respect to the optimized homogeneous, i.e. non-graded, and monotonically graded material. The numerical results show a shifting of the perfect absorption peak to lower frequencies or a widening of the perfect absorption frequency range for graded materials when compared to uniform ones. The results are validated experimentally on 3D-printed samples therefore confirming the relevance of such gradient along with the efficiency of the control of the entire design process. a) [email protected]

Lessons learned developing a massive open online course in implementation research in infectious diseases of poverty in low- and middle-income countries

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420This study uses a case study approach to examine the development of a massive open online course (MOOC) on intervention and implementation research in infectious diseases of poverty for learners in low- and middle-income countries (LMICs). Implementation research (IR) seeks to understand and address barriers to effective implementation of health interventions, strategies, and policies. In recent years, IR has attracted increased interest, and corresponding demand for training, however, current training opportunities are not easily accessible to learners in LMICs. In 2017, the MOOC was introduced to a diverse range of learners to enhance access to training materials and has been offered yearly since. Findings are based on the experiences of the MOOC working group which included developers and facilitators, and on interpretations of data such as forum discussion activity and Facebook posts. The use of material from local contexts and in local languages, and professional facilitation of discussion forums was identified by the working group to be key considerations in developing the MOOC. Other findings include the importance of using clear instructions and preparing discussion questions to stimulate learner engagement. These findings add to the limited knowledge of MOOCs developed for LMICs and are of value to others developing professional development MOOCs in LMIC health contexts.http://doi.org/10.5944/openpraxis.13.1.117213pubpub

Parathyroid Hormone Mediates Hematopoietic Cell Expansion through Interleukin-6

Parathyroid hormone (PTH) stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6) is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L), PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45+ and CD11b+ cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls) but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin- Sca-1+c-Kit+ (LSK) hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance