Neuroendocrine control of a dynamic communication signal

Multiple physiological systems regulate the electric communication signal of the weakly electric gymnotiform fish, Brachyhypopomus pinnicaudatus. Fish were injected with neuroendocrine probes which identified pharmacologically relevant serotonin (5-HT) receptors similar to the mammalian 5-HT1AR and 5-HT2AR. Peptide hormones of the hypothalamic-pituitary-adrenal/interrenal axis also augment the electric waveform. These results indicate that the central serotonergic system interacts with the hypothalamic-pituitary-interrenal system to regulate communication signals in this species. The same neuroendocrine probes were tested in females before and after introducing androgens to examine the relationship between sex steroid hormones, the serotonergic system, melanocortin peptides, and EOD modulations. Androgens caused an increase in female B. pinnicaudatus responsiveness to other pharmacological challenges, particularly to the melanocortin peptide adrenocorticotropic hormone (ACTH). A forced social challenge paradigm was administered to determine if androgens are responsible for controlling the signal modulations these fish exhibit when they encounter conspecifics. Males and females responded similarly to this social challenge construct, however introducing androgens caused implanted females to produce more exaggerated responses. These results confirm that androgens enhance an individual's capacity to produce an exaggerated response to challenge, however another unidentified factor appears to regulate sex-specific behaviors in this species. These results suggest that the rapid electric waveform modulations B. pinnicaudatus produces in response to conspecifics are situation-specific and controlled by activation of different serotonin receptor types and the subsequent effect on release of pituitary hormones.

Development of a dynamic headspace concentration technique for the non-contact sampling of human odor samples and the creation of canine training aids

Human scent and human remains detection canines are used to locate living or deceased humans under many circumstances. Human scent canines locate individual humans on the basis of their unique scent profile, while human remains detection canines locate the general scent of decomposing human remains. Scent evidence is often collected by law enforcement agencies using a Scent Transfer Unit, a dynamic headspace concentration device. The goals of this research were to evaluate the STU-100 for the collection of human scent samples, and to apply this method to the collection of living and deceased human samples, and to the creation of canine training aids. The airflow rate and collection material used with the STU-100 were evaluated using a novel scent delivery method. Controlled Odor Mimic Permeation Systems were created containing representative standard compounds delivered at known rates, improving the reproducibility of optimization experiments. Flow rates and collection materials were compared. Higher air flow rates usually yielded significantly less total volatile compounds due to compound breakthrough through the collection material. Collection from polymer and cellulose-based materials demonstrated that the molecular backbone of the material is a factor in the trapping and releasing of compounds. The weave of the material also affects compound collection, as those materials with a tighter weave demonstrated enhanced collection efficiencies. Using the optimized method, volatiles were efficiently collected from living and deceased humans. Replicates of the living human samples showed good reproducibility; however, the odor profiles from individuals were not always distinguishable from one another. Analysis of the human remains samples revealed similarity in the type and ratio of compounds. Two types of prototype training aids were developed utilizing combinations of pure compounds as well as volatiles from actual human samples concentrated onto sorbents, which were subsequently used in field tests. The pseudo scent aids had moderate success in field tests, and the Odor pad aids had significant success. This research demonstrates that the STU-100 is a valuable tool for dog handlers and as a field instrument; however, modifications are warranted in order to improve its performance as a method for instrumental detection.

A diagnostic framework for demand amplification problems in supply chains

This dissertation delivers a framework to diagnose the Bull-Whip Effect (BWE) in supply chains and then identify methods to minimize it. Such a framework is needed because in spite of the significant amount of literature discussing the bull-whip effect, many companies continue to experience the wide variations in demand that are indicative of the bull-whip effect. While the theory and knowledge of the bull-whip effect is well established, there still is the lack of an engineering framework and method to systematically identify the problem, diagnose its causes, and identify remedies. ^ The present work seeks to fill this gap by providing a holistic, systems perspective to bull-whip identification and diagnosis. The framework employs the SCOR reference model to examine the supply chain processes with a baseline measure of demand amplification. Then, research of the supply chain structural and behavioral features is conducted by means of the system dynamics modeling method. ^ The contribution of the diagnostic framework, is called Demand Amplification Protocol (DAMP), relies not only on the improvement of existent methods but also contributes with original developments introduced to accomplish successful diagnosis. DAMP contributes a comprehensive methodology that captures the dynamic complexities of supply chain processes. The method also contributes a BWE measurement method that is suitable for actual supply chains because of its low data requirements, and introduces a BWE scorecard for relating established causes to a central BWE metric. In addition, the dissertation makes a methodological contribution to the analysis of system dynamic models with a technique for statistical screening called SS-Opt, which determines the inputs with the greatest impact on the bull-whip effect by means of perturbation analysis and subsequent multivariate optimization. The dissertation describes the implementation of the DAMP framework in an actual case study that exposes the approach, analysis, results and conclusions. The case study suggests a balanced solution between costs and demand amplification can better serve both firms and supply chain interests. Insights pinpoint to supplier network redesign, postponement in manufacturing operations and collaborative forecasting agreements with main distributors.^

Aquatic fauna as indicators for Everglades restoration: Applying dynamic targets in assessments

A major goal of the Comprehensive Everglades Restoration Plan (CERP) is to recover historical (pre-drainage) wading bird rookeries and reverse marked decreases in wading bird nesting success in Everglades National Park. To assess efforts to restore wading birds, a trophic hypothesis was developed that proposes seasonal concentrations of small-fish and crustaceans (i.e., wading bird prey) were a key factor to historical wading bird success. Drainage of the Everglades has diminished these seasonal concentrations, leading to a decline in wading bird nesting and displacing them from their historical nesting locations. The trophic hypothesis predicts that restoring historical hydrological patterns to pre-drainage conditions will recover the timing and location of seasonally concentrated prey, ultimately restoring wading bird nesting and foraging to the southern Everglades. We identified a set of indicators using small-fish and crustaceans that can be predicted from hydrological targets and used to assess management success in regaining suitable wading bird foraging habitat. Small-fish and crustaceans are key components of the Everglades food web and are sensitive to hydrological management, track hydrological history with little time lag, and can be studied at the landscape scale. The seasonal hydrological variation of the Everglades that creates prey concentrations presents a challenge to interpreting monitoring data. To account for the variable hydrology of the Everglades in our assessment, we developed dynamic hydrological targets that respond to changes in prevailing regional rainfall. We also derived statistical relationships between density and hydrological drivers for species representing four different life-history responses to drought. Finally, we use these statistical relationships and hydrological targets to set restoration targets for prey density. We also describe a report-card methodology to communicate the results of model-based assessments for communication to a broad audience.

Neuroendocrine control of a dynamic communication signal

Multiple physiological systems regulate the electric communication signal of the weakly electric gymnotiform fish, Brachyhypopomuspinnicaudatus. Fish were injected with neuroendocrine probes which identified pharmacologically relevant serotonin (5-HT) receptors similar to the mammalian 5-HT1AR and 5-HT2AR. Peptide hormones of the hypothalamic-pituitary-adrenal/interrenal axis also augment the electric waveform. These results indicate that the central serotonergic system interacts with the hypothalamic-pituitaryinterrenal system to regulate communication signals in this species. The same neuroendocrine probes were tested in females before and after introducing androgens to examine the relationship between sex steroid hormones, the serotonergic system, melanocortin peptides, and EOD modulations. Androgens caused an increase in female B. pinnicaudatus responsiveness to other pharmacological challenges, particularly to the melanocortin peptide adrenocorticotropic hormone (ACTH). A forced social challenge paradigm was administered to determine if androgens are responsible for controlling the signal modulations these fish exhibit when they encounter conspecifics. Males and females responded similarly to this social challenge construct, however introducing androgens caused implanted females to produce more exaggerated responses. These results confirm that androgens enhance an individual's capacity to produce an exaggerated response to challenge, however another unidentified factor appears to regulate sex-specific behaviors in this species. These results suggest that the rapid electric waveform modulations B. pinnicaudatus produces in response to conspecifics are situation-specific and controlled by activation of different serotonin receptor types and the subsequent effect on release of pituitary hormones.

Dynamic Compartmentalization of Persistent UPEC in the Superficial Bladder Epithelium

Urinary tract infections (UTIs) are typically caused by bacteria that colonize different regions of the urinary tract, mainly the bladder and the kidney. Approximately 25% of women that suffer from UTIs experience a recurrent infection within 6 months of the initial bout, making UTIs a serious economic burden resulting in more than 10 million hospital visits and $3.5 billion in healthcare costs in the United States alone. Type-1 fimbriated Uropathogenic E. coli (UPEC) is the major causative agent of UTIs, accounting for almost 90 % of bacterial UTIs. The unique ability of UPEC to bind and invade the superficial bladder epithelium allows the bacteria to persist inside epithelial niches and survive antibiotic treatment. Persistent, intracellular UPEC are retained in the bladder epithelium for long periods, making them a source of recurrent UTIs. Hence, the ability of UPEC to persist in the bladder is a matter of major health and economic concern, making studies exploring the underlying mechanism of UPEC persistence highly relevant.

In my thesis, I will describe how intracellular Uropathogenic E.coli (UPEC) evade host defense mechanisms in the superficial bladder epithelium. I will also describe some of the unique traits of persistent UPEC and explore strategies to induce their clearance from the bladder. I have discovered that the UPEC virulence factor Alpha-hemolysin (HlyA) plays a key role in the survival and persistence of UPEC in the superficial bladder epithelium. In-vitro and in-vivo studies comparing intracellular survival of wild type (WT) and hemolysin deficient UPEC suggested that HlyA is vital for UPEC persistence in the superficial bladder epithelium. Further in-vitro studies revealed that hemolysin helped UPEC persist intracellularly by evading the bacterial expulsion actions of the bladder cells and remarkably, this virulence factor also helped bacteria avoid t degradation in lysosomes.

To elucidate the mechanistic basis for how hemolysin promotes UPEC persistence in the urothelium, we initially focused on how hemolysin facilitates the evasion of UPEC expulsion from bladder cells. We found that upon entry, UPEC were encased in “exocytic vesicles” but as a result of HlyA expression these bacteria escaped these vesicles and entered the cytosol. Consequently, these bacteria were able to avoid expulsion by the cellular export machinery.

Since bacteria found in the cytosol of host cells are typically recognized by the cellular autophagy pathway and transported to the lysosomes where they are degraded, we explored why this was not the case here. We observed that although cytosolic HlyA expressing UPEC were recognized and encased by the autophagy system and transported to lysosomes, the bacteria appeared to avoid degradation in these normally degradative compartments. A closer examination of the bacteria containing lysosomes revealed that they lacked V-ATPase. V-ATPase is a well-known proton pump essential for the acidification of mammalian intracellular degradative compartments, allowing for the proper functioning of degradative proteases. The absence of V-ATPase appeared to be due to hemolysin mediated alteration of the bladder cell F-actin network. From these studies, it is clear that UPEC hemolysin facilitates UPEC persistence in the superficial bladder epithelium by helping bacteria avoid expulsion by the exocytic machinery of the cell and at the same time enabling the bacteria avoid degradation when the bacteria are shuttled into the lysosomes.

Interestingly even though UPEC appear to avoid elimination from the bladder cell their ability to multiple in bladder cells seem limited.. Indeed, our in-vitro and in-vivo experiments reveal that UPEC survive in superficial bladder epithelium for extended periods of time without a significantly change in CFU numbers. Indeed, we observed these bacteria appeared quiescent in nature. This observation was supported by the observation that UPEC genetically unable to enter a quiescence phase exhibited limited ability to persist in bladder cells in vitro and in vivo, in the mouse bladder.

The studies elucidated in this thesis reveal how UPEC toxin, Alpha-hemolysin plays a significant role in promoting UPEC persistence via the modulation of the vesicular compartmentalization of UPEC at two different stages of the infection in the superficial bladder epithelium. These results highlight the importance of UPEC Alpha-hemolysin as an essential determinant of UPEC persistence in the urinary bladder.

Oil Market Modelling: A Comparative Analysis of Fundamental and Latent Factor Approaches

We formally compare fundamental factor and latent factor approaches to oil price modelling. Fundamental modelling has a long history in seeking to understand oil price movements, while latent factor modelling has a more recent and limited history, but has gained popularity in other financial markets. The two approaches, though competing, have not formally been compared as to effectiveness. For a range of short- medium- and long-dated WTI oil futures we test a recently proposed five-factor fundamental model and a Principal Component Analysis latent factor model. Our findings demonstrate that there is no discernible difference between the two techniques in a dynamic setting. We conclude that this infers some advantages in adopting the latent factor approach due to the difficulty in determining a well specified fundamental model.

A generic strategy for dynamic load balancing of distributed memory parallel computational mechanics using unstructured meshes

A large class of computational problems are characterised by frequent synchronisation, and computational requirements which change as a function of time. When such a problem is solved on a message passing multiprocessor machine [5], the combination of these characteristics leads to system performance which deteriorate in time. As the communication performance of parallel hardware steadily improves so load balance becomes a dominant factor in obtaining high parallel efficiency. Performance can be improved with periodic redistribution of computational load; however, redistribution can sometimes be very costly. We study the issue of deciding when to invoke a global load re-balancing mechanism. Such a decision policy must actively weigh the costs of remapping against the performance benefits, and should be general enough to apply automatically to a wide range of computations. This paper discusses a generic strategy for Dynamic Load Balancing (DLB) in unstructured mesh computational mechanics applications. The strategy is intended to handle varying levels of load changes throughout the run. The major issues involved in a generic dynamic load balancing scheme will be investigated together with techniques to automate the implementation of a dynamic load balancing mechanism within the Computer Aided Parallelisation Tools (CAPTools) environment, which is a semi-automatic tool for parallelisation of mesh based FORTRAN codes.

Dynamic fator Models for bivariate Count Data: an application to fire activity

The study of forest re activity, in its several aspects, is essencial to understand the phenomenon and to prevent environmental public catastrophes. In this context the analysis of monthly number of res along several years is one aspect to have into account in order to better comprehend this tematic. The goal of this work is to analyze the monthly number of forest res in the neighboring districts of Aveiro and Coimbra, Portugal, through dynamic factor models for bivariate count series. We use a bayesian approach, through MCMC methods, to estimate the model parameters as well as to estimate the common latent factor to both series.

Innovation from below: dynamic capabilities of the territory as a source for new social ventures

Social innovation is a critical factor for the conception of new strategies to deal with increasingly complex social problems. Many of these initiatives are pursued at the local level and are based on the dynamic capabilities of a given territory. Through the analysis of the Cooperative Terra Chã, we assess whether dynamic capabilities of a territory can generate opportunities for social innovation and how they can be exploited by local communities. We observe that by using a integrated strategy for the management of the capabilities of a territory, new social ventures are able to cope with severe social issues that are not being adequately addressed by other stakeholders.

Molecular analysis of exons 8, 9 and 10 of the fibroblast growth factor receptor 2 (FGFR2) gene in two families with index cases of Apert Syndrome

Introduction: Apert syndrome (AS) is a craniosynostosis condition caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2) gene. Clinical features include cutaneous and osseous symmetric syndactily in hands and feet, with variable presentations in bones, brain, skin and other internal organs. Methods: Members of two families with an index case of Apert Syndrome were assessed to describe relevant clinical features and molecular analysis (sequencing and amplification) of exons 8, 9 and 10 of FGFR2 gen. Results: Family 1 consists of the mother, the index case and half -brother who has a cleft lip and palate. In this family we found a single FGFR2 mutation, S252W, in the sequence of exon 8. Although mutations were not found in the study of the patient affected with cleft lip and palate, it is known that these diseases share signaling pathways, allowing suspected alterations in shared genes. In the patient of family 2, we found a sequence variant T78.501A located near the splicing site, which could interfere in this process, and consequently with the protein function.

Integrating the age factor in designing industrial environments and workstations in the workforce ageing era

As people spend a third of their lives at work and, in most cases, indoors, the work environment assumes crucial importance. The continuous and dynamic interaction between people and the working environment surrounding them produces physiological and psychological effects on operators. Recognizing the substantial impact of comfort and well-being on employee satisfaction and job performance, the literature underscores the need for industries to implement indoor environment control strategies to ensure long-term success and profitability. However, managing physical risks (i.e., ergonomic and microclimate) in industrial environments is often constrained by production and energy requirements. In the food processing industry, for example, the safety of perishable products dictates storage temperatures that do not allow for operator comfort. Conversely, warehouses dedicated to non-perishable products often lack cooling systems to limit energy expenditure, reaching high temperatures in the summer period. Moreover, exceptional events, like the COVID-19 pandemic, introduce new constraints, with recommendations impacting thermal stress and respiratory health. Furthermore, the thesis highlights how workers' variables, particularly the aging process, reduce tolerance to environmental stresses. Consequently, prolonged exposure to environmental stress conditions at work results in cardiovascular disease and musculoskeletal disorders. In response to the global trend of an aging workforce, the thesis bridges a literature gap by proposing methods and models that integrate the age factor into comfort assessment. It aims to present technical and technological solutions to mitigate microclimate risks in industrial environments, ultimately seeking innovative ways to enhance the aging workforce's comfort, performance, experience, and skills. The research outlines a logical-conceptual scheme with three main areas of focus: analyzing factors influencing the work environment, recognizing constraints to worker comfort, and designing solutions. The results significantly contribute to science by laying the foundation for new research in worker health and safety in an ageing working population's extremely current industrial context.

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

New Microsatellite Markers For Wild And Commercial Species Of Passiflora (passifloraceae) And Cross-amplification.

• We developed the first microsatellites for Passiflora setacea and characterized new sets of markers for P. edulis and P. cincinnata, enabling further genetic diversity studies to support the conservation and breeding of passion fruit species. • We developed 69 microsatellite markers and, in conjunction with assessments of cross-amplification using primers available from the literature, present 43 new polymorphic microsatellite loci for three species of Passiflora. The mean number of alleles per locus was 3.1, and the mean values of the expected and observed levels of heterozygosity were 0.406 and 0.322, respectively. • These microsatellite markers will be valuable tools for investigating the genetic diversity and population structure of wild and commercial species of passion fruit (Passiflora spp.) and may be useful for developing conservation and improvement strategies by contributing to the understanding of the mating system and hybridization within the genus.