The role of protein oxidation in ageing & disease

Ageing is a natural phenomenon of the human lifecycle, yet it is still not understood what causes the deterioration of the human body near the end of the lifespan. One popular theory is the Free Radical Theory of Ageing, which proposes that oxidative damage to biomolecules causes ageing of tissues. The ageing population is affected by many chronic diseases. This study focused on sarcopenia (muscle loss in ageing) and obesity as two models for comparison of oxidative damage in muscle proteins in mice. The aim of the study was to develop advanced mass spectrometry methods to detect specific oxidative modifications to mouse muscle proteins, including oxidation, nitration, chlorination, and carbonyl group formation, but western blotting was also used to provide complementary information on the oxidative state of proteins from aged and obese muscle. Mass spectrometry proved to be a powerful tool, enabling identification of the types of modifications present, the sites at which they were present and percentage of the peptide populations that were modified. Targeted and semi-targeted mass spectrometry methods were optimised for the identification and quantitation of the oxidised residues in muscle proteins. The development of the quantitative methods enabled comparisons of mass spectrometry instruments. Both the Time of Flight and QTRAP systems showed advantages of using the different mass analysers to quantify oxidative modifications. Several oxidised residues were characterised and quantified in both the obese and sarcopenic models, and higher levels of oxidation were found compared to their control counterparts. Residues found to be oxidised were oxidation of proline, tyrosine and tryptophan, dioxidation of methionine, allysine and nitration of tyrosine. However quantification was performed on methionine dioxidation and cysteine trioxidation containing residues in SERCA. The combination of measuring residue susceptibility and functional studies could contribute to understanding the overall role of oxidation in ageing and obesity.

Analyse de spectres FUSE d'étoiles naines blanches riches en hélium et mesure de leur abondance en carbone

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The effects of crystallization on the pulsations of white dwarf stars

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

A completely kinematostatically decoupled XY compliant parallel manipulator through new topology structure

This paper deals with a completely kinematostaticaly decoupled XY compliant parallel manipulator (CPM) composed of exactly-constrained compliant modules. A new 4-PP XY translational parallel mechanism (TPM) with a new topology structure is firstly proposed where each two P (P: prismatic) joints on the base in two non-adjacent legs are rigidly connected. A novel 4-PP XY CPM is then obtained by replacing each traditional P join on the base in the 4-PP XY TPM with a compound basic parallelogram module (CBPM) and replacing each traditional P joint on the motion stage with a basic parallelogram module (BPM). Approximate analytical model is derived with comparison to the FEA (finite element analysis) model and experiment for a case study. The proposed novel XY CPM has a compact configuration with good dynamics, and is able to well constrain the parasitic rotation and the cross-axis coupling of the motion stage. The cross-axis motion of the input stage can be completely eliminated, and the lost motion between the input stage and the motion stage is significantly reduced.

Analyse de spectres FUSE d'étoiles naines blanches riches en hélium et mesure de leur abondance en carbone

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The effects of crystallization on the pulsations of white dwarf stars

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

A Micro-Opto-Electro-Mechanical System (MOEMS) for Microstructure Manipulation

Microstructure manipulation is a fundamental process to the study of biology and medicine, as well as to advance micro- and nano-system applications. Manipulation of microstructures has been achieved through various microgripper devices developed recently, which lead to advances in micromachine assembly, and single cell manipulation, among others. Only two kinds of integrated feedback have been demonstrated so far, force sensing and optical binary feedback. As a result, the physical, mechanical, optical, and chemical information about the microstructure under study must be extracted from macroscopic instrumentation, such as confocal fluorescence microscopy and Raman spectroscopy. In this research work, novel Micro-Opto-Electro-Mechanical-System (MOEMS) microgrippers are presented. These devices utilize flexible optical waveguides as gripping arms, which provide the physical means for grasping a microobject, while simultaneously enabling light to be delivered and collected. This unique capability allows extensive optical characterization of the structure being held such as transmission, reflection, or fluorescence. The microgrippers require external actuation which was accomplished by two methods: initially with a micrometer screw, and later with a piezoelectric actuator. Thanks to a novel actuation mechanism, the “fishbone”, the gripping facets remain parallel within 1 degree. The design, simulation, fabrication, and characterization are systematically presented. The devices mechanical operation was verified by means of 3D finite element analysis simulations. Also, the optical performance and losses were simulated by the 3D-to-2D effective index (finite difference time domain FDTD) method as well as 3D Beam Propagation Method (3D-BPM). The microgrippers were designed to manipulate structures from submicron dimensions up to approximately 100 µm. The devices were implemented in SU-8 due to its suitable optical and mechanical properties. This work demonstrates two practical applications: the manipulation of single SKOV-3 human ovarian carcinoma cells, and the detection and identification of microparts tagged with a fluorescent “barcode” implemented with quantum dots. The novel devices presented open up new possibilities in the field of micromanipulation at the microscale, scalable to the nano-domain.

Map of North African dust emission

Changes in the emission, transport and deposition of aeolian dust have profound effects on regional climate, so that characterizing the lifecycle of dust in observations and improving the representation of dust in global climate models is necessary. A fundamental aspect of characterizing the dust cycle is quantifying surface dust fluxes, yet no spatially explicit estimates of this flux exist for the World's major source regions. Here we present a novel technique for creating a map of the annual mean emitted dust flux for North Africa based on retrievals of dust storm frequency from the Meteosat Second Generation Spinning Enhanced Visible and InfraRed Imager (SEVIRI) and the relationship between dust storm frequency and emitted mass flux derived from the output of five models that simulate dust. Our results suggest that 64 (±16)% of all dust emitted from North Africa is from the Bodélé depression, and that 13 (±3)% of the North African dust flux is from a depression lying in the lee of the Aïr and Hoggar Mountains, making this area the second most important region of emission within North Africa.

Building Information Modelling in UK Construction Projects: A State of the Art Review

This paper aims to present a state-of-the-art review of the scope and practical implications of the Building Information Modelling (BIM) platform in the UK construction practice. Theoretical developments suggest that BIM is an integration of both product and process innovation, not just a disparate set of software tools. BIM provides effective collaboration, visual representation and data management, which enable the smooth flow of information throughout the project’s lifecycle. The most frequently reported benefits are related to Capital Cost (capex) and Operational costs (opex) and time savings. Key challenges, however, focus on the interoperability of software, capital installation costs, in-house experience, client preference and cultural issues within design teams and within the organisation. The paper concludes with a critical commentary on the changing roles and a process required to implement BIM in UK construction projects, and suggests areas for further research.

Development of a knowledge sharing framework for improving the testing processes in global product development

As identified by Griffin (1997) and Kahn (2012), manufacturing organisations typically improve their market position by accelerating their product development (PD) cycles. One method for achieving this is to reduce the time taken to design, test and validate new products, so that they can reach the end customer before competition. This paper adds to existing research on PD testing procedures by reporting on an exploratory investigation carried out in a UK-based manufacturing plant. We explore the organisational and managerial factors that contribute to the time spent on testing of new products during development. The investigation consisted of three sections, viz. observations and process modelling, utilisation metrics and a questionnaire-based investigation, from which a proposed framework to improve and reduce the PD time cycle is presented. This research focuses specifically on the improvement of the utilisation of product testing facilities and the links to its main internal stakeholders - PD engineers.

D9.5 – Exploitation Plan (version 1 of 3)

The RAGE Exploitation Plan is a living document, to be upgraded along the project lifecycle, supporting RAGE partners in defining how the results of the RAGE RIA will be used both in commercial and non-comercial settings. The Exploitation Plan covers the entire process from the definition of the business case for the RAGE Ecosystem to the creation of the sustainability conditions for its real-world operation beyond the H2020 project co-funding period. The Exploitation Plan will be published in three incremental versions, due at months 18, 36 and 42 of the project lifetime. This early stage version 1 of 3 is mainly devoted to: i. Setting-up the structure and the initial building blocks to be populated and completed in the future editions of the Exploitation Plan and to ii. providing additional guidance for market intelligence gathering, business modelling definition and validation, outreach and industry engagement and ultimately providing insights for the development, validation and evaluation of RAGE results across the project´s workplan execution. These tasks will in turn render suitable inputs to enhance the two future editions of the Exploitation Plan.

Tegument Glycoproteins and Cathepsins of Newly Excysted Juvenile Fasciola hepatica Carry Mannosidic and Paucimannosidic N-glycans

Recently, the prevalence of Fasciola hepatica in some areas has increased considerably and the availability of a vaccine to protect livestock from infection would represent a major advance in tools available for controlling this disease. To date, most vaccine-target discovery research on this parasite has concentrated on proteomic and transcriptomic approaches whereas little work has been carried out on glycosylation. As the F. hepatica tegument (Teg) may contain glycans potentially relevant to vaccine development and the Newly Excysted Juvenile (NEJ) is the first lifecycle stage in contact with the definitive host, our work has focused on assessing the glycosylation of the NEJTeg and identifying the NEJTeg glycoprotein repertoire. After in vitro excystation, NEJ were fixed and NEJTeg was extracted. Matrix-assisted laser desorption ionisation-time of flight-mass spectrometry (MALDI-TOF-MS) analysis of released N-glycans revealed that oligomannose and core-fucosylated truncated N-glycans were the most dominant glycan types. By lectin binding studies these glycans were identified mainly on the NEJ surface, together with the oral and ventral suckers. NEJTeg glycoproteins were affinity purified after targeted biotinylation of the glycans and identified using liquid chromatography and tandem mass spectrometry (LC-MS/MS). From the total set of proteins previously identified in NEJTeg, eighteen were also detected in the glycosylated fraction, including the F. hepatica Cathepsin B3 (FhCB3) and two of the Cathepsin L3 (FhCL3) proteins, among others. To confirm glycosylation of cathepsins, analysis at the glycopeptide level by LC-ESI-ion-trap-MS/MS with collision-induced dissociation (CID) and electron-transfer dissociation (ETD) was carried out. We established that cathepsin B1 (FhCB1) on position N80, and FhCL3 (BN1106_s10139B000014, scaffold10139) on position N153, carry unusual paucimannosidic Man2GlcNAc2 glycans. To our knowledge, this is the first description of F. hepatica NEJ glycosylation and the first report of N-glycosylation of F. hepatica cathepsins. The significance of these findings for immunological studies and vaccine development is discussed.

Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Towards a Contingency Theory perspective of Quality Management in Enabling Strategic Alignment

The aim of this paper is to explore the role of Quality Management (QM) theory and practice using a contingency theory perspective. The study is grounded in the role of QM in improving strategic alignment within Small and Medium Sized Enterprises (SMEs) using Contingency Theory rather than adopting best practice approaches. An inductive theory building research methodology was used involving multiple case analyses of five SMEs, involving repeat interviews (n=45), focus groups (n=5) and document analysis. From the findings, it was found that Contingency Variables (strategy, culture, lifecycle and customer focus) and their respective typologies were found to interact with QM practices in helping to shape strategic alignment between the SMEs and their environments. This shaping process based on contingency approaches occurred in a manner unique to each SME and their respective environments rather than in an overarching best practice manner.