Both hypertrophic (HCM) and dilated cardiomyopathy (DCM), though differing in their aetiologies, share features of impaired resting energetics. The aim of this thesis was to determine if cardiac high energy phosphate metabolism, measured as the phosphocreatine (PCr)/ATP ratio using 31Phosphorus magnetic resonance spectroscopy (31P MRS), is further impaired during exercise in these pathologies. This would provide a possible explanation for the high incidence of exercise related death in HCM and DCM as well as the blunted inotropic response to exercise in DCM. Furthermore, this thesis investigates the role of stress perfusion and stress tissue oxygenation in HCM (as these are hypothesized to exacerbate the primary defect in energetics) and exercise training in DCM (which is hypothesized to improve function though the mechanisms are uncertain). This work developed a novel protocol for measuring 31P MRS in a clinically acceptable time frame. The traditional acquisition is at least 20 minutes (as much as 40 minutes in subjects with lower pulse rates). This is a particularly long time to allow for exercise in the magnet particularly in the symptomatic DCM cohort. Hence this work meticulously developed a shorter 8 minute protocol. Its validity, reproducibility and application to exercise were confirmed. The post processing of the MRS data was further improved for calculating blood contamination and tested with both simulated and patient data, including normal, hypertrophied and thinned myocardium. Applying this new method, this thesis is the first to report a further decrease in exercise energetics in HCM. The relationship between perfusion, tissue de-oxygenation and energetic compromise during exercise was then explored in HCM. Athletes, with physiological hypertrophy, were used as an additional control group in these experiments. These results demonstrated a strikingly blunted oxygenation response of the HCM heart to stress even in the pre-hypertrophy HCM mutation carriers. However, as a group, the data did not show a correlation between the blunted oxygenation response and the percentage change in PCr/ATP during exercise. None-the-less, these results can potentially be useful for distinguishing between hypertrophy in the athletes and pathological hypertrophy in HCM and for distinguishing HCM mutation carriers’ pre hypertrophy and the normal heart. In the DCM cohort, this thesis explored the impact of exercise training on cardiac metabolism and function. The results showed no change in cardiac energetics and left ventricular ejection fraction during 8 minutes of exercise. In addition, an eight week home exercise programme did not alter resting or exercise cardiac PCr/ATP, but improved cardiac function during rest and exercise, and increased exercise tolerance and quality of life scores. In conclusion, this thesis reports further insights into cardiac exercise energetics in HCM and DCM and its relationship to perfusion and oxygenation in HCM and to exercise training in DCM. Therapies that decrease the energy cost of cardiac work during exercise may prove beneficial targets to explore further in these conditions.

Thesis advisor: Thomas N. Seyfried / Mycoplasmas are the smallest, self-replicating free-living prokaryotes, and have been associated with carcinogenesis. Mycoplasmas can be detected in a high percentage of a wide variety of primary human cancers. Some mycoplasma species such as M. fermentans and M. hyorhinis can transform normal murine and human cell lines into tumorigenic cells. Mycoplasma infection can activate oncogenes as well as inactivate tumor suppressor genes. These observations suggest that mycoplasmas can be both carcinogenic and or onco-modulatory. I found that the metastatic macrophage VM-M3 cell line (referred to as M3+) was infected with mycoplasmas. Mycoplasmal16S rDNA sequencing showed M3+ cells were infected by the mycoplasma species M. arginini. Antibiotic was used to eradicate M. arginini from M3+ cells (referred to as M3- cells). The energetics of the infected M3+ cells and the non-infected M3- cells was studied by measuring respiration (oxygen consumption) and fermentation (lactate production). Respiration was enhanced and fermentation was reduced in the M3- cells compared to the M3+ cells. Glucose enhanced the fermentation and reduced the respiration of both the M3+ and the M3- cells. The M3+ cells produced higher quantities of metabolites indicative of immunological activation (itaconic acid, succinate, and citrulline) compared to M3- cells. In addition, in-vitro proliferation was higher in the M3+ cells than in the M3- cells at high cell densities. Primary subcutaneous tumor growth and metastasis was less in mice inoculated with the M3- cells than with the M3+ cells. The survival of a VM mouse was longer when inoculated with the M3- cells compared to the M3+ cells. Altogether these data indicates that M. arginini is an onco-modulator associated with activation, deregulated energetics and enhanced tumor progression of VM-M3 metastatic macrophage cells. / Thesis (MS) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Energy Regulatory Office Abstract Energy regulatory office (ERO) was established in 2001 by Act No. 458/2000 Coll., on business conditions and public administration in the energy sectors and on amendment to other laws as an independent specialized authority of the state administration for the regulation of energy sector and pricing authority in the field of energy. Among its main goals include prices regulation, licenses management, supervision performance over duties observance that licence - holders follow from law regulations and from ACER's resolution, European comittee's and ERO's, controls executions and in case of disharmony between desirable and real behavior of stowing remedy sancitons investigation performance of competition requirements concerning electricity or gas in markets, information providing and dissension decision - making like subject supporting alternative dissension on disputes in power - engineering branch. The aim of this thesis is to present the ERO as a whole with the approaching of its activities with a focus on defining its competence in relation to the environment, because humanity's depedence on energy brings with it negative effects that can lead to the disappearance of civilization. I tis therefore necessary to link the energy and environmental sectors and to direct the...

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Orientador: Ariovaldo Pereira da Cruz Neto / Banca: José Eduardo de Carvalho / Banca: Sérgio Furtado dos Reis / Banca: Denis Otávio Vieira de Andrade / Banca: Luciano Martins Verdade / Resumo: O presente estudo versa sobre energética alimentar de um animal. O estudo procurou analisar, dentre outras coisas, os fatores intrínsecos e extrínsecos que respondem pela variabilidade na taxa metabólica em repouso (TMR) e a relação entre esta variação e padrões de história de vida de um marsupial (Gracilinanus microtarsus). Especificamente, a variabilidade da TMR seria determinada através de um aspecto especifico da história de vida, a dieta. Aspectos como possíveis efeitos da dinâmica de variação das reservas energéticas sobre esta relação também foram analisados. Utilizando metodologia apropriada também analisamos a variação da disponibilidade e qualidade da dieta. Variações desses fatores induzem modificações na condição corpórea e, desta forma, os efeitos desta variável sobre a TMR mediariam um dos objetivos do estudo, servindo como elemento de ligação para averiguar quais componentes da condição corpórea seriam responsáveis pela variabilidade na TMR. / Abstract: The present study turns about energetics to feed of an animal. The study analyzed, among other things, the intrinsic and extrinsic factors that answer for the variability in the resting metabolic rate (RMR) and the relationship between this variation and patterns of life history of a marsupial (Gracilinanus microtarsus). Specifically, the variability of RMR would be determined through an aspect specify of the life history, the diet. Aspects as possible effects of the dynamics of variation of the energy budge about this relationship were also analyzed. Using appropriate methodology also analyzed the variation of the availability and quality of the diet. Variations of those factors induce modifications in the body condition and, this way, the effects of this variable on RMR would mediate one of the objectives of the study, serving as connection element to discover which components of the body condition would be responsible for the variability in RMR. / Doutor

This thesis presents work on the deposition of nanothermite using a piezoelectric inkjet printer, focusing on the effects of printing parameters and sample geometry on burning rate. The ability of the printer to produce consistent droplet size and spacing was shown to have repeatable droplet size and sub-millimeter precision in droplet spacing. The droplet-droplet interaction of the nanothermite ink was examined, and a printing frequency of 10 Hz was shown to produce smooth and consistent geometry in the printed samples. The primary printing parameter varied in this study was the pixel pitch (i.e., the distance between printed droplets). As pixel pitch decreased (i.e., the droplets are printed closer together) in both directions (x- and y-directions), the burning rate increased, and as sample width increased the burning rate increased. A significant number of samples (476) were printed and demonstrated consistent, energetic performance; this indicated favorable high-volume production capabilities. A thermal model was developed based on an energy balance for the printed nanothermite samples. The model accurately predicted the burning rate trends observed in the experimental results. This result indicated that the increase in heat generation in both the thicker (pixel-pitch studies) and wider samples decreased the significance of heat loss to the environment. The statistically significant results presented in this work, along with a descriptive thermal model, increase the fundamental understanding of the effects of printed geometry and droplet spacing on nanothermite energetic performance.

Behavioral activiti es and predatory behavior of 18 American Kestrels (Falco sparverius, 9 males and 9 females) were observed for 350+ hours during 3 seasons (nonbreeding = Jan-Feb , breeding = mid-~lar-Apr, and postbreeding = late-Aug-Sept) in northern Utah. Daily energy expenditure (DEE) of male and female kestrels was estimated with a model that incorporated flight activity data from free-living birds and laboratory measurements on daytime and nighttime metabolic rates and energy costs of tissue production derived from captive kestrels. Production costs were included in the DEE for breeding and postbreeding kestrels. The energy cost of gonadal growth for males (0.02 kcal/day) and females (0.20 kcal/day) was added to the DEE of breeding kestrels. Breeding females expended an estimated 10.13 kcal/day for producing an average clutch of 4.5 eggs. The energy costs of fat deposition (2.27 and 4.39 kcal / day for males and females, respectively) and molt (2.38 and 2.72 kcal/day for males and females , respectively) were added to the DEE of postbreeding kestrels. In addition to the DEE , the model predicted nonflight energy expenditure (NFEE) and flight energy expenditure (FEE) during the day, and energy expenditure during the night (NEE). DEE of nonbreeding birds is generally higher (47.71 kcal/day) than those from the breeding (44.89 kcal / day) and postbreeding (42.42 kcal / day) seasons. DEE of females (48.69 kcal/day) is higher than males (41.31 kcal/day) primarily because females averaged 15.5% heavier than males during all 3 seasons, and females have higher costs of production. Kestrels are heaviest during the nonbreeding season and the amount of metabolizable energy available is highest. DEE is lower during the breeding and postbreeding seasons because thermoregulatory demands have decreased which may allow energy to be metabolized for production. NFEE accounts for most (48.5%) of the DEE. Flight costs are relatively small because kestrels allocate an average 3% of the photoperiod (25.6 min/day) to flight activities. Egg production accounts for 20% of the DEE of breeding females. The energy cost of fat deposition and molt accounts for 11.6 and 15.9% of the DEE for postbreeding males and females, respectively. These reproductive and tissue production costs may also elevate the DEE of breeding and postbreeding females to that of nonbreeding females.

Interface modeling is a critical aspect in any multi-material system modeling. Even a small change in the interface model may lead to significant changes in material behavior of the microscale, and these changes may transfer up to higher scales influencing the strain and stress fields, and damaging behavior in the macroscale material. This work focuses on the effects of different interface models in nanocomposites composed of carbon nanotubes in polymer matrix materials and their applications as nanocomposite binders in energetic materials. These material systems include materials that span multiple scales from nano to macroscale, and thus require a detailed multiscale analysis. A hierarchical multiscale framework is employed here, where the effective material properties from subscales are obtained by solving the subscale boundary value problem. The information obtained from the subscale simulations are transferred up to higher scales to be used as input properties. A nonlocal continuum mechanics framework known as peridynamics is used to perform the computational simulations. Peridynamics uses integro-differential equations for conservation laws instead of partial differential equations as in the classical continuum mechanics. This makes it possible for peridynamics to inherently account for nonlocal effects such as damage initiation, crack growth, and crack branching without any modifications such as element deletion, adaptive mesh refinement, using enrichment functions and so on, which are commonly used in other numerical methods. Peridynamics is a particle-based method where the particles are allowed to interact with other particles within their horizon which serves as a cut-off distance for forming particle-to-particle bonds and therefore defines the extent of nonlocality. Peridynamics has different formulations regarding the bond interactions. A bond-based peridynamics framework is used here. A verified and validated in-house code is used for the simulations. The simulations for the carbon nanotube and nanofiber-based nanocomposites, and for nanocomposite bonded energetic materials start from the microscale and range up to the macroscale. For only the carbon nanotube-polymer nanocomposites, the interfaces include the CNT-polymer interfaces. For the energetic materials, the interfaces consider the CNT-polymer interfaces in the microscale and the grain-nanocomposite binder interfaces in the mesoscale. Peridynamics, being a nonlocal continuum mechanics method, by default will have nonlocal interfaces. The material systems investigated in this work first use different nonlocal interfaces in peridynamics which consider the bond between two particles at the interface to be connected in series or in parallel. The nonlocal interface model in peridynamics makes it challenging to control the interface properties and leads to fuzzy interfaces, i.e. interfaces of finite thickness. In this work, a local cohesive interface model is implemented in the peridynamics framework. Cohesive zones were originally used for modeling the growth of cracks by introducing cohesive forces that hold the crack surfaces together, thereby removing the stress singularity problem in linear elastic fracture mechanics. The idea of cohesive zones are applied to peridynamics interfaces, which introduces locality into the nonlocal framework. This interface model does not only remove the nonlocality at the peridynamics interfaces, but it leads to a higher fidelity interface model that is controllable by the user. The differences between the nonlocal and local interfaces are studied in detail in different scales and for different material systems. Implementing a local model into a nonlocal framework brings some challenges, namely obtaining and calibrating the cohesive interface properties for the materials used, the numerical problems with material interpenetration in extreme compression, and very small time steps that are required to resolve the material response. Some remedies are proposed for the problems encountered. The cohesive zone model used in this work can have different functional forms in normal and tangential direction to reflect differences in opening mode and frictional sliding behaviors. / Doctor of Philosophy / Multi-material systems have interface regions where a transition from one material to another occurs. How the interface region is modeled can change the response of a material to external loads even if the interface model is slightly different. This work focuses on the effect of different interface models in nanocomposites based on carbon nanotubes and in nanocomposite bonded energetic materials. These material systems include materials that span multiple scales from nano to the macroscale, and thus require a detailed multiscale analysis. Multiscale analysis of a material means analyzing the material at each scale that is involved for the given material system separately and passing relevant information between the scales. A hierarchical multiscale framework is employed here which is based on a bottom-up approach, where the material properties are obtained at the smaller scales and passed up to the larger scales to be used as the input properties. A nonlocal continuum mechanics in the form of peridynamics is used to perform the computational simulations. The nonlocality stems from the fact that the particles can interact not only with their closest neighbors, but with other particles within their horizon, which is the cut-off distance that dictates how far a material particle can make bonds with other particles. The main advantage of peridynamics is to be able to model cracks without any a priori knowledge about crack growth directions or patterns. Peridynamics has different formulations for representing the bond interactions. A bond-based peridynamics framework is used here. A verified and validated in-house code is used for the simulations. The simulations for the carbon nanotube-polymer nanocomposites and nanocomposite bonded energetic materials take place starting from the microscale up to the macroscale. For the carbon nanotube nanocomposite scale, the interfaces include the fiber-matrix interfaces. For the nanocomposite bonded energetic materials, the interfaces considered include the fiber-matrix interfaces in the microscale and the grain-binder interfaces in the mesoscale. Peridynamics, being a nonlocal continuum mechanics method, nominally includes nonlocal interfaces. The material systems investigated in this work first use different nonlocal interfaces in peridynamics which consider the bond between two particles at the interface to be connected in series or in parallel. The nonlocal interface model in peridynamics makes it challenging to control the interface properties and leads to fuzzy, or finite thickness interfaces. A local cohesive interface model is implemented in the peridynamics framework. Cohesive zones are originally used for modeling cracks by introducing cohesive forces that hold the crack surfaces together to remove the stress singularity at the crack in classical linear elastic fracture mechanics. The idea of cohesive zones are applied to peridynamics interfaces which introduces locality into the nonlocal framework. This interface model does not only remove the nonlocality at the peridynamics interfaces, but it leads to a higher fidelity interface model that is controllable by the user. The differences between the nonlocal and local interfaces are studied in detail in different scales and for different material systems. Implementing a local model into a nonlocal framework brings some challenges, namely obtaining and calibrating the cohesive interface properties for the materials used, the numerical problems with material interpenetration in extreme compression, and very small time steps that are required to resolve the material response. Some remedies are proposed to address these issues. The cohesive zone model used in this work have different mathematical models in normal and tangential directions. It is therefore capable of modeling mechanical and thermal problems including frictional heating. The mechanical results obtained by using cohesive interfaces show potential for developing similar local interface models for thermal and electrical conduction allowing for the expanded application of the approach to multiphysics problems in multiscale composite materials.

A series of phosphotripeptide ligands for the Grb2 SH2 domain was designed and synthesized, each of which derived from the minimal consensus sequence required for binding: Ac-pYXN. The binding affinity and related thermodynamic parameters were determined by isothermal titration calorimetry. Both the size and connectivity of the side-chain was varied. The consequences of incorporating α,α-disubstitution at the pY+1 residue on binding thermodynamics were evaluated, as were the effects of constraining the side-chains in a ring. The series was evaluated from a number of perspectives: (1) increasing size of the pY+1 residue by utilizing various amino acid types: monoalkyl, dialkyl, or cycloalkyl; (2) comparisons between ligands with the same number of carbons (scission control); and (3) by comparing ligands incorporating cyclic pY+1 residues with those incorporating α,α-dialkyl residues with one fewer methylene group (excision control). Inconsistencies in the thermodynamic consequence of constraining the backbone were observed within this set of ligands, which reveal the limitations of our understanding of protein-ligand interactions. Aspects of both the classical and non-classical hydrophobic effect were observed, but the occurance of one over the other could not be explained. / text