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No / Prohormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.

Indoor wireless communication systems are becoming increasingly prevalent in work environments. The need to quickly and efficiently provide in-building and microcellular coverage without sacrificing quality is critical to cellular and emerging personal communication system (PCS) operators. Traditionally, indoor wireless communication system design has been carried out by human experts relying on experience to determine a satisfactory system configuration. This thesis describes the algorithms and technical considerations implemented in a comprehensive propagation planning tool, SMT Plus, which has been designed to predict the coverage regions of both in-building and microcellular wireless communication systems. The goal of SMT Plus is to provide both wireless service providers and equipment manufacturers with an efficient, easy-to-use coverage prediction tool for use in the design of any indoor or campus-wide wireless system. Using site-specific building information combined with on-site signal strength measurements, the tool provides system planners with a highly accurate model of the propagation environment among a group of buildings. SMT Plus provides a comprehensive solution to the planning and installation of wireless communication systems in and around buildings. / Master of Science

Assessment of potentially contaminated sites (PCS) can be expensive; hence, simple and less demanding methods and models are required. This work attempts to provide an approach that can aid in selecting the most appropriate model for the PCS. The developed method uses over 100 field site data to evaluate four test models (analytical/empirical) that provide the maximum plume length (Lmax), which is used as a principal model ranking quantity in this work. Analysis of site data shows that field plume length (Lf) follows a log-normal distribution. Subsequently, Lmax is delineated with respect to Lf using a threshold probability as underestimating, overestimating, and overly-overestimating. Akaike information criterion (AIC) and analytical hierarchy process (AHP) are considered to support the threshold approach results. The classical AIC is modified (to AICmod) to fit the term represented by the difference between Lf and Lmax. Additionally, the threshold factors as a product of subjective weights are added to the AICmod. Using Lf and Lmax, the AICmod provides a distinct ranking of the test models. For the AHP approach, the goodness of fit, underestimation, overly overestimation, and model complexity are the four chosen criteria. Similar to AICmod, the AHP approach provides a distinct ranking of the test models. The final decision on the best fitting model can be made on user criteria following the scheme developed in this work.

Acinetobacter baumannii est un pathogène opportuniste qui prend une importance clinique croissante du fait de l’acquisition de multi-résistance. Nous avons étudié chez A. baumannii les caractéristiques et la régulation des intégrons de classe 1 (IM1) qui sont des systèmes génétiques favorisant l’acquisition, l’expression et la dissémination des gènes de résistance aux antibiotiques. Nous avons montré qu’il existe une prédominance des promoteurs des cassettes Pc fort in vivo dans une collection d’isolats cliniques et d’environnement hospitalier et in silico dans les IM1 chez A. baumannii. Nous avons aussi montré que l’expression des Pc chez A. baumannii est 4 fois plus faible que chez E. coli, quel que soit le variant de Pc. Deux explications sont possibles pour la sélection des Pc forts chez A. baumannii : (i) la nécessité d’avoir un niveau d’expression suffisant en clinique pour survivre à la pression de sélection antibiotique et (ii) la nécessité d’une régulation de l’expression de l’intégrase, représentant un coût biologique important. En effet, A. baumannii ne possède pas le système de répression par LexA existant chez E. coli. Nos résultats ouvrent le champ de l’étude de la régulation des IM1 chez A. baumannii et ainsi l’identification de nouvelles voies d’action pour lutter contre l’antibio-résistance / Acinetobacter baumannii is an opportunistic pathogen of increasing clinical importance due to the acquisition of multi-resistance. We studied in A. baumannii the characteristics and regulation of class 1 integrons (IM1), which are genetic systems that favor the acquisition, expression and dissemination of antibiotic resistance genes. We have shown that there is a predominance of strong Pc cassette promoters, in vivo, in a collection of clinical and hospital environment isolates, and in silico, from A. baumannii IM1 published in NCBI. We have also shown that the expression of Pc in A. baumannii is 4-fold lower than in E. coli, regardless of the Pc variant. Explanations that can be raised for the selection of strong Pc in A. baumannii are: (i) the need for a sufficient level of antibiotic resistance expression to survive the selection pressure in clinical environment; and (ii) the need for regulation of the integrase expression, which is of significant biological cost. Indeed A. baumannii does not have the LexA repression system existing in E. coli. Our results open the field of the study of IM1 regulation in A. baumannii and thus the identification of new pathways to fight antibiotic resistance.

When Department of Defense (DoD) personnel receive orders to relocate to a new duty installation, nearly one third abandon their companion animals, which negatively affects the local shelters' costs, personnel, and capabilities to provide quality care for shelter animals. There is a lack of research on relevant policies among local government policy makers, installation commanders, directors of animal shelters, and animal rights advocates about the abandonment of companion animals by DoD personnel. The purpose of this qualitative descriptive case study was to investigate the relationship between the influx of abandoned DoD companion animals and the management and logistical (including financial) operations of 2 publicly funded animal shelters near a Midwest DoD installation. The theoretical framework was Merton's theory of unintended consequences. Data were collected through interviews with 2 shelter directors, 10 surveys completed by shelter personnel, and a review of the shelters' logistical and financial documents spanning fiscal years 2013 - 2014. Data were analyzed after coding for themes and patterns. According to study findings, the abandonment of companion animals by DoD personnel has a negative impact on the shelters' finances, shelter personnel workload and stress, and the quality of life for incoming animals as well as those already in the shelters. The implications for positive social change are to inform policy makers of the importance of implementing policies to keep DoD companion animals with families, thereby easing transitions for those at risk, which helps to maintain the financial solvency of animal shelters, reduce stress for shelter personnel, and help companion animals to adjust as they are adopted into new homes.

Background and aims: The provenance of post-concussion symptoms (PCS) and post-traumatic stress (PTSD) after mild traumatic brain injury (mTBI) is controversial. This thesis investigated factors influencing these two conditions separately, as well as the interplay between PCS and PTSD, in individuals with mTBI and a control sample without mTBI (orthopaedic injuries). Method: Consecutive adult attendees of an Emergency Department with mTBI or orthopaedic injury were prospectively recruited and completed the Rivermead Post-concussion Questionnaire (RPQ) and Trauma Screening Questionnaire (TSQ) for PTSD at two weeks (T1) and three months (T2) post-injury. The sample at T1 consisted of 34 with complicated mTBI, 76 with uncomplicated mTBI and 47 with orthopaedic injury, and 18 with complicated mTBI, 43 with uncomplicated mTBI and 33 orthopaedic controls at T2. Results: Although there were no differences in overall PCS symptomology between groups, a subset of PCS symptoms (headaches, dizziness and nausea) was found to be specific to mTBI at both time points. These symptoms are proposed to have a neurological basis, as opposed to a psychological basis. PTSD interacted with PCS, particularly in mTBI, such that PTSD was associated with greater “neurogenic” and “psychogenic” symptomology in this group, but only a moderate increase in psychogenic symptoms for controls. A model of the influence of PTSD on PCS is presented. PTSD was influenced by poor memory quality for the traumatic event and attribution of blame to others, but not by mTBI. Discussion and conclusions: Though mTBI may set the scene for at least neurogenic symptoms of PCS to occur, psychological mechanisms, particularly PTSD, have a significant role in the persistence of PCS. Our findings suggest the need for a clear story and sense of meaning for a traumatic event for good recovery from PTSD. Taken together, the results suggest that psychological interventions, particularly aimed at PTSD, may be most effective after mTBI.

No description available.

When Department of Defense (DoD) personnel receive orders to relocate to a new duty installation, nearly one third abandon their companion animals, which negatively affects the local shelters' costs, personnel, and capabilities to provide quality care for shelter animals. There is a lack of research on relevant policies among local government policy makers, installation commanders, directors of animal shelters, and animal rights advocates about the abandonment of companion animals by DoD personnel. The purpose of this qualitative descriptive case study was to investigate the relationship between the influx of abandoned DoD companion animals and the management and logistical (including financial) operations of 2 publicly funded animal shelters near a Midwest DoD installation. The theoretical framework was Merton's theory of unintended consequences. Data were collected through interviews with 2 shelter directors, 10 surveys completed by shelter personnel, and a review of the shelters' logistical and financial documents spanning fiscal years 2013 - 2014. Data were analyzed after coding for themes and patterns. According to study findings, the abandonment of companion animals by DoD personnel has a negative impact on the shelters' finances, shelter personnel workload and stress, and the quality of life for incoming animals as well as those already in the shelters. The implications for positive social change are to inform policy makers of the importance of implementing policies to keep DoD companion animals with families, thereby easing transitions for those at risk, which helps to maintain the financial solvency of animal shelters, reduce stress for shelter personnel, and help companion animals to adjust as they are adopted into new homes.

Two novel antenna designs for mobile handsets are proposed in this thesis. With a helix loading, an inverted-L monopole antenna capable of generating two resonances at about 900 and 1850 MHz is first presented. The operating bandwidths obtained cover the required bandwidths of the GSM/DCS/PCS bands. Besides, an internal mobile handset antenna comprising a PIFA and a PILA, which are, respectively, designed for covering the GSM and DCS/PCS bands is also presented. The PIFA and PILA together occupy a compact volume of 7.2 ¡Ñ 20 ¡Ñ 40 mm3, and are suitable to be built-in within the housing of a mobile handset.