Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.

A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis.

Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.

Upon activation, T cells require energy for growth, proliferation, and function. Effector T (Teff) cells, such as Th1 and Th17 cells, utilize high levels of glycolytic metabolism to fuel proliferation and function. In contrast, Treg cells require oxidative metabolism to fuel suppressive function. It remains unknown how Teff/Treg-cell metabolism is altered when nutrients are limited and leptin levels are low. We therefore examined the role of malnutrition and associated hypoleptinemia on Teff versus Treg cells. We found that both malnutrition-associated hypoleptinemia and T cell-specific leptin receptor knockout suppressed Teff-cell number, function, and glucose metabolism, but did not alter Treg-cell metabolism or suppressive function. Using the autoimmune mouse model EAE, we confirmed that fasting-induced hypoleptinemia altered Teff-cell, but not Treg-cell, glucose metabolism, and function in vivo, leading to decreased disease severity. To explore potential mechanisms, we examined HIF-1α, a key regulator of Th17 differentiation and Teff-cell glucose metabolism, and found HIF-1α expression was decreased in T cell-specific leptin receptor knockout Th17 cells, and in Teff cells from fasted EAE mice, but was unchanged in Treg cells. Altogether, these data demonstrate a selective, cell-intrinsic requirement for leptin to upregulate glucose metabolism and maintain function in Teff, but not Treg cells.

Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.

BACKGROUND: Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel. METHODS AND RESULTS: Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs. CONCLUSIONS: Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.

Comparaison entre la dérive de VO₂ et de FC chez des sujets de deux niveaux d'endurance

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

S332 pump station, south of TS/Ph-1, Taylor Slough

This material is based upon work supported by the National Science Foundation through the Florida Coastal Everglades Long-Term Ecological Research program under Cooperative Agreements #DBI-0620409 and #DEB-9910514. This image is made available for non-commercial or educational use only.

Psychometric properties of the Drive for Muscularity Scale in Malay men

The Drive for Muscularity Scale (DMS) is a widely used measure in studies of men’s body image, but few studies have examined its psychometric properties outside English-speaking samples. Here, we assessed the factor structure of a Malay translation of the DMS. A community sample of 159 Malay men from Kuala Lumpur, Malaysia, completed the DMS, along with measures of self-esteem, body appreciation, and muscle discrepancy. Exploratory factor analysis led to the extraction of two factors, differentiating attitudes from behaviours, which mirrors the parent scale. Both factors also loaded on to a higher-order drive for muscularity factor. The subscales of the Malay DMS had adequate internal consistencies and good convergent validity, insofar as significant relationships were reported with self-esteem, body appreciation,muscle discrepancy, and body mass index. These results indicate that the Malay DMS has acceptable psychometric properties and can be used to assess body image concerns in Malay men.

Implementation of a drive-by monitoring system for transport infrastructure utilising GNSS

Ageing and deterioration of infrastructure is a challenge facing transport authorities. In particular, there is a need for increased bridge monitoring in order to provide adequate maintenance, prioritise allocation of funds and guarantee acceptable levels of transport safety. Existing bridge structural health monitoring (SHM) techniques typically involve direct instrumentation of the bridge with sensors and equipment for the measurement of properties such as frequencies of vibration. These techniques are important as they can indicate the deterioration of the bridge condition. However, they can be labour intensive and expensive due to the requirement for on-site installations. In recent years, alternative low-cost indirect vibrationbased SHM approaches have been proposed which utilise the dynamic response of a vehicle to carry out “drive-by” pavement and/or bridge monitoring. The vehicle is fitted with sensors on its axles thus reducing the need for on-site installations. This paper investigates the use of low-cost sensors incorporating global navigation satellite systems (GNSS) for implementation of the drive-by system in practice, via field trials with an instrumented vehicle. The potential of smartphone technology to be harnessed for drive by monitoring is established, while smartphone GNSS tracking applications are found to compare favourably in terms of accuracy, cost and ease of use to professional GNSS devices.

Investigating Feasibility of Drive-by Bridge Monitoring by Laboratory Experiments

A potentially powerful drive-by bridge inspection approach was proposed to inspect bridge conditions utilizing the vibrations of a test vehicle while it passes over the target bridge. This approach suffers from the effect of roadway surface roughness and two solutions were proposed in previous studies: one is to subtract the responses of two vehicles (time-domain method) before spectral analysis and the other one is to subtract the spectrum of one vehicle from that of the other (frequency-domain method). Although the two methods were verified theoretically and numerically, their practical effectiveness is still an open question.Furthermore, whether the outcome spectra processed by those methods could be used to detect potential bridge damage is of our interests. In this study, a laboratory experiment was carried out with a test tractor-trailer system and a scaled bridge. It was observed that, first, for practical applications, it would be preferable to apply the frequency-domain method, avoiding the need to meet a strict requirement in synchronizing the responses of the two trailers in time domain; second, the statistical pattern of the processed spectra in a specific frequency band could be an effective anomaly indicator incorporated in drive-by inspection methods.

The Development of Entrepreneurial Drive During the University Business School Experience

This research investigates changes in entrepreneurial drive (ED) between each of the three-year levels of students at an undergraduate UK university business school in order to test this measurement construct within a European context. The research adopted a quantitative approach to determine whether the ED measurement instrument could identify differences in the students’ ED dimensions and the overall ED across the three different years of undergraduate study. The data was subjected to principle component analysis to create factor scores for the ED components and the multivariate analysis of variance tests to determine whether different year groups exhibited different levels of ED. The research found that the total ED score increased at each successive year level. In addition, the achievement motivation, proactive disposition, and self-efficacy factors (dimensions) all increased during the university experience. As such, this research confirms the value of the ED measurement instrument in assessing the development of entrepreneurial drive within a European higher education setting.

Predicting Muscularity-Related Behavior, Emotions, and Cognitions in Men: The Role of Psychological Need Thwarting, Drive for Muscularity, and Mesomorphic Internalization

We examine the relationships that internalization, need thwarting (NT), and drive for muscularity (DFM), along with their interactions, had with weightlifting, muscle dissatisfaction (MD), and muscle-related-worry (MRW). A sample of 552 men (MAGE = 20.5 years, SD = 3.1) completed the Psychological Need Thwarting Scale, the Internalization subscale of the male version of the Sociocultural Attitudes Towards Appearance Questionnaire, the Drive for Muscularity Scale-Attitudes subscale, the Male Body Attitudes Scale-Muscularity subscale, the Body Change Inventory-Worry subscale, and an inventory assessing weightlifting behavior. DFM significantly predicted weightlifting, MRW, and MD. Internalization significantly predicted weightlifting and MRW. NT significantly predicted weightlifting and MD, and its relationship with MRW approached significance. The interaction terms did not predict weightlifting or MRW. The NT/DFM and NT/Internalization interaction terms predicted MD. These results highlight the role of NT in predicting appearance variables in men.

Soluzioni per il controllo delle testine di lettura/scrittura in hard disk drive magnetici

Questa tesi descrive alcune tecniche realizzative e algoritmi di controllo per il posizionamento delle testine di lettura/scrittura in hard disk drive magnetici. Viene presentata l'attuazione a due stadi delle testine per incrementare la banda frequenziale del sistema, in cui un motore VCM funge da primo stadio e come secondo stadio si utilizza un microattuatore, di tipo piezoelettrico o elettromagnetico o elettrotermico. Il posizionamento della testina sulle tracce magnetiche dei dischi contenenti i dati si divide in due fasi: track-seeking e track-following, che presentano diversi requisiti di velocità e precisione, per questo motivo si descrive il metodo dello switching control. Successivamente viene formulato un modello matematico nello spazio degli stati degli stati dell'attuatori a due stadi e il relativo controllo in retroazione, basato su osservatore dello stato. Inoltre per il track-seeking si propone il controllo a due gradi di libertà e per il track-following il metodo del disaccoppiamento della sensitività. Infine si riportano due novità tecnologiche per gli hard disk magnetici: l'attuazione a tre stadi, che sfrutta un secondo microattuatore, di tipo termico, e gli hard disk riempiti d'elio ed ermeticamente sigillati, che semplificano il controllo grazie alla minore turbolenza del gas e al suo minor peso.

“It’s the People That Drive It”: Motivating and Supporting Collaborative Data Use Practices in Three Teacher Education Programs

Thesis (Ph.D.)--University of Washington, 2016-08

Searching for Masculine Capital: Experiences Leading to High Drive for Muscularity in Men

Studies on the drive for muscularity (DFM) have primarily been quantitative, focused on identifying correlates. Currently little is known about men’s experiences leading them to desire high levels of muscle and engage in behaviours to increase their masculine capital. Our purpose was to explore the stories of men with high DFM revealing the socio-cultural and personal factors leading to DFM and their search for masculine capital. In-depth life-history interviews and multiple in-the-field conversations were undertaken with twenty men (Mean age=28.45, SD=6.96, years) scoring ≥ 3 on the Drive for Muscularity Scale (Mean=4.30, SD=0.70). Men’s stories focused on a set of dysfunctional childhood and adolescent socio-cultural interactions, including forms of symbolic violence, between them and significant others. In these interactions men were exposed to dominant social narratives of masculinity, and through comparisons and reinforcement they identified discrepancies between themselves and these narratives. In late adolescence and early adulthood men came to believe that they lacked masculine capital. Men struggled to increase their masculine capital through engagement with other traditional masculine activities (e.g., sport) and driven by activating events, they compensated through DFM desires and behaviours. This study advances knowledge by revealing the socio-cultural and personal processes participants believed led to their high DFM. Findings disclose that men’s search for masculine capital may have led them to develop and maintain high levels of DFM.

CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P. aeruginosa strains PA14. As defective mexR is a genetic trait associated with the clinical emergence of nalB-type multidrug resistance in P. aeruginosa during antibiotic treatment, we investigated the involvement of CpxR in regulating multidrug resistance among resistant isolates generated in the laboratory via antibiotic treatment and collected in clinical settings. CpxR is required to activate expression of mexAB-oprM and enhances drug resistance, in the absence or presence of MexR, in ofloxacin-cefsulodin-resistant isolates generated in the laboratory. Furthermore, CpxR was also important in the mexR-defective clinical isolates. The newly identified regulatory linkage between CpxR and the MexAB-OprM efflux pump highlights the presence of a complex regulatory network modulating multidrug resistance in P. aeruginosa.

Development of variable displacement oil pump for internal combustion engines

In the last years the need to develop more environmentally friendly and efficient cars as led to the development of several technologies to improve the performance of internal combustion engines, a large part of the innovations are focused in the auxiliary systems of the engine, including, the oil pump, this is an element of great importance in the dynamics of the engine as well a considerable energy consumer. Most solutions for oil pumps to this day are fixed displacement, for medium and high speeds, the pump flow rate is higher than the needs of the engine, this excess flow leads to the need for recirculation of the fluid which represents a waste of energy. Recently, technological advances in this area have led to the creation of variable displacement oil pumps, these have become a 'must have' due to the numerous advantages they bring, although the working principle of vane or piston pumps is relatively well known, the application of this technology for the automotive industry is new and brings new challenges. The focus of this dissertation is to develop a new concept of variable displacement system for automotive oil pumps. The main objective is to obtain a concept that is totally adaptable to existing solutions on the market (engines), both dimensionally as in performance specifications, having at the same time an innovative mechanical system for obtaining variable displacement. The developed design is a vane pump with variable displacement going in line with existing commercial solutions, however, the variation of the eccentricity commonly used to provide an variable displacement delivery is not used, the variable displacement is achieved without varying the eccentricity of the system but with a variation of the length of the pumping chamber. The principle of operation of the pump is different to existing solutions while maintaining the ability to integrate standard parts such as control valves and mechanical safety valves, the pump is compatible with commercial solutions in terms of interfaces for connection between engine systems and pump. A concept prototype of the product was obtained in order to better evaluate the validity of the concept. The developed concept represents an innovation in oil pumps design, being unique in its mechanical system for variable displacement delivery.