Modelling and Validation of a Mass Imbalance Oscillation Generator to Harvest Heart Motion Energy

An autonomous energy source within a human body is of key importance in the development of medical implants. This work deals with the modelling and the validation of an energy harvesting device which converts the myocardial contractions into electrical energy. The mechanism consists of a clockwork from a commercially available wrist watch. We developed a physical model which is able to predict the total amount of energy generated when applying an external excitation. For the validation of the model, a custom-made hexapod robot was used to accelerate the harvesting device along a given trajectory. We applied forward kinematics to determine the actual motion experienced by the harvesting device. The motion provides translational as well as rotational motion information for accurate simulations in three-dimensional space. The physical model could be successfully validated.

Jatropha mahafalensis for rural energy supply in south-western Madagascar?

In many parts of the eastern African region wood-based fuels will remain dominant sources of energy in coming decades. Pressure on forests, especially in semi-arid areas will therefore continue increasing. In this context, the role of liquid biofuels as substitutes for firewood and charcoal, to help reducing pressure on woody biomass and contributing to a better energy security of rural communities, has remained controversial among researchers and practitioners. At household level, the economic and technical feasibility of straight vegetable oil (SVO) was assessed mainly on Jatropha curcas, with unpersuasive results. So far nothing is known about the suitability as an energy carrier of Jatropha mahafalensis Jum. & H. Perrier, the only endemic representative of the Jatropha genus in Madagascar. This paper explores the potential of this plant as a biofuel feedstock in the agro-pastoral area of Soalara, in the semi-arid south-western part of Madagascar. Only hedge-based production was considered to rule out competition over land with food crops. Yield data, the length of currently existing hedges and energy consumption patterns of households were used to assess the quantitative potential and economic viability of J. mahafalensis SVO for lighting and cooking. Tests were conducted with cooking and lighting devices to assess their technical suitability at household level. The paper concludes that J. mahafalensis hedges have some potential to replace paraffin for lighting (though without much economic benefit for the concerned households), but not to replace charcoal or firewood for cooking. The paper recommends that rural energy strategies in similar contexts do not focus only on substituting current fuels with SVO, but should also take into consideration other alternatives. In the case of cooking, there seems to be substantially more potential in increasing the efficiency of current fuel production and consumption technologies (kilns and stoves); and in the case of lighting, solutions based on SVO need to be compared against other options such as portable solar devices.

Energy Efficient Multimedia Communications in IEEE 802.11 Networks

During the last decade wireless mobile communications have progressively become part of the people’s daily lives, leading users to expect to be “alwaysbest-connected” to the Internet, regardless of their location or time of day. This is indeed motivated by the fact that wireless access networks are increasingly ubiquitous, through different types of service providers, together with an outburst of thoroughly portable devices, namely laptops, tablets, mobile phones, among others. The “anytime and anywhere” connectivity criterion raises new challenges regarding the devices’ battery lifetime management, as energy becomes the most noteworthy restriction of the end-users’ satisfaction. This wireless access context has also stimulated the development of novel multimedia applications with high network demands, although lacking in energy-aware design. Therefore, the relationship between energy consumption and the quality of the multimedia applications perceived by end-users should be carefully investigated. This dissertation addresses energy-efficient multimedia communications in the IEEE 802.11 standard, which is the most widely used wireless access technology. It advances the literature by proposing a unique empirical assessment methodology and new power-saving algorithms, always bearing in mind the end-users’ feedback and evaluating quality perception. The new EViTEQ framework proposed in this thesis, for measuring video transmission quality and energy consumption simultaneously, in an integrated way, reveals the importance of having an empirical and high-accuracy methodology to assess the trade-off between quality and energy consumption, raised by the new end-users’ requirements. Extensive evaluations conducted with the EViTEQ framework revealed its flexibility and capability to accurately report both video transmission quality and energy consumption, as well as to be employed in rigorous investigations of network interface energy consumption patterns, regardless of the wireless access technology. Following the need to enhance the trade-off between energy consumption and application quality, this thesis proposes the Optimized Power save Algorithm for continuous Media Applications (OPAMA). By using the end-users’ feedback to establish a proper trade-off between energy consumption and application performance, OPAMA aims at enhancing the energy efficiency of end-users’ devices accessing the network through IEEE 802.11. OPAMA performance has been thoroughly analyzed within different scenarios and application types, including a simulation study and a real deployment in an Android testbed. When compared with the most popular standard power-saving mechanisms defined in the IEEE 802.11 standard, the obtained results revealed OPAMA’s capability to enhance energy efficiency, while keeping end-users’ Quality of Experience within the defined bounds. Furthermore, OPAMA was optimized to enable superior energy savings in multiple station environments, resulting in a new proposal called Enhanced Power Saving Mechanism for Multiple station Environments (OPAMA-EPS4ME). The results of this thesis highlight the relevance of having a highly accurate methodology to assess energy consumption and application quality when aiming to optimize the trade-off between energy and quality. Additionally, the obtained results based both on simulation and testbed evaluations, show clear benefits from employing userdriven power-saving techniques, such as OPAMA, instead of IEEE 802.11 standard power-saving approaches.

Implications of the sustainable development paradigm for Switzerland

The sustainable development paradigm raises issues of global, intra- and intergenerational social equity as well as respect for nature, and economic welfare. Switzerland is confronted by these issues within its own country, and has a moral responsibility vis-a-vis the rest of the world. Syndromes of global change are affecting many eco-regions, not only in developing and transition countries, but to a lesser extent also the affluent countries. Switzerland as a nation has an impact on syndromes through its far-reaching economic activities, which are non-sustainable. At the global level, more modest consumption patterns, a considerably slowed demographic change, a nonconsumptive but sustainable use of natural resources, and conflict transformation are the main prerequisites for improving sustainability. Switzerland's current contribution to sustainability is much less than what it could be, hence the need for additional action along general principles in,accordance with Swiss traditions and innovative potentials. A number of concrete actions could be taken immediately. These are: labelling the socially and ecologically sustainable production of goods and services, and their negotiation at WTO level; enhancing international cooperation and research; strengthening education and research for sustainability, and emphasizing energy and material flux efficiency at home and abroad.

Multiple gradient echo propeller (MGREP) MRI: Technical development and potential applications

The PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) magnetic resonance imaging (MRI) technique has inherent advantages over other fast imaging methods, including robust motion correction, reduced image distortion, and resistance to off-resonance effects. These features make PROPELLER highly desirable for T2*-sensitive imaging, high-resolution diffusion imaging, and many other applications. However, PROPELLER has been predominantly implemented as a fast spin-echo (FSE) technique, which is insensitive to T2* contrast, and requires time-inefficient signal averaging to achieve adequate signal-to-noise ratio (SNR) for many applications. These issues presently constrain the potential clinical utility of FSE-based PROPELLER. ^ In this research, our aim was to extend and enhance the potential applications of PROPELLER MRI by developing a novel multiple gradient echo PROPELLER (MGREP) technique that can overcome the aforementioned limitations. The MGREP pulse sequence was designed to acquire multiple gradient-echo images simultaneously, without any increase in total scan time or RF energy deposition relative to FSE-based PROPELLER. A new parameter was also introduced for direct user-control over gradient echo spacing, to allow variable sensitivity to T2* contrast. In parallel to pulse sequence development, an improved algorithm for motion correction was also developed and evaluated against the established method through extensive simulations. The potential advantages of MGREP over FSE-based PROPELLER were illustrated via three specific applications: (1) quantitative T2* measurement, (2) time-efficient signal averaging, and (3) high-resolution diffusion imaging. Relative to the FSE-PROPELLER method, the MGREP sequence was found to yield quantitative T2* values, increase SNR by ∼40% without any increase in acquisition time or RF energy deposition, and noticeably improve image quality in high-resolution diffusion maps. In addition, the new motion algorithm was found to improve the performance considerably in motion-artifact reduction. ^ Overall, this work demonstrated a number of enhancements and extensions to existing PROPELLER techniques. The new technical capabilities of PROPELLER imaging, developed in this thesis research, are expected to serve as the foundation for further expanding the scope of PROPELLER applications. ^

Integrating sequence information in microarray data analysis by free energy modeling

Microarray technology is a high-throughput method for genotyping and gene expression profiling. Limited sensitivity and specificity are one of the essential problems for this technology. Most of existing methods of microarray data analysis have an apparent limitation for they merely deal with the numerical part of microarray data and have made little use of gene sequence information. Because it's the gene sequences that precisely define the physical objects being measured by a microarray, it is natural to make the gene sequences an essential part of the data analysis. This dissertation focused on the development of free energy models to integrate sequence information in microarray data analysis. The models were used to characterize the mechanism of hybridization on microarrays and enhance sensitivity and specificity of microarray measurements. ^ Cross-hybridization is a major obstacle factor for the sensitivity and specificity of microarray measurements. In this dissertation, we evaluated the scope of cross-hybridization problem on short-oligo microarrays. The results showed that cross hybridization on arrays is mostly caused by oligo fragments with a run of 10 to 16 nucleotides complementary to the probes. Furthermore, a free-energy based model was proposed to quantify the amount of cross-hybridization signal on each probe. This model treats cross-hybridization as an integral effect of the interactions between a probe and various off-target oligo fragments. Using public spike-in datasets, the model showed high accuracy in predicting the cross-hybridization signals on those probes whose intended targets are absent in the sample. ^ Several prospective models were proposed to improve Positional Dependent Nearest-Neighbor (PDNN) model for better quantification of gene expression and cross-hybridization. ^ The problem addressed in this dissertation is fundamental to the microarray technology. We expect that this study will help us to understand the detailed mechanism that determines sensitivity and specificity on the microarrays. Consequently, this research will have a wide impact on how microarrays are designed and how the data are interpreted. ^

Alterations in redox and energy metabolism in Ras-transformed cells: Mechanisms and therapeutic implications

Increasing attention has been given to the connection between metabolism and cancer. Under aerobic conditions, normal cells predominantly use oxidative phosphorylation for ATP generation. In contrast, increase of glycolytic activity has been observed in various tumor cells, which is known as Warburg effect. Cancer cells, compared to normal cells, produce high levels of Reactive Oxygen Species (ROS) and hence are constantly under oxidative stress. Increase of oxidative stress and glycolytic activity in cancer cells represent major biochemical alterations associated with malignant transformation. Despite prevalent upregulation of ROS production and glycolytic activity observed in various cancer cells, underlying mechanisms still remain to be defined. Oncogenic signals including Ras has been linked to regulation of energy metabolism and ROS production. Current study was initiated to investigate the mechanism by which Ras oncogenic signal regulates cellular metabolism and redox status. A doxycycline inducible gene expression system with oncogenic K-ras transfection was constructed to assess the role played by Ras activation in any given studied parameters. Data obtained here reveals that K-ras activation directly caused mitochondrial dysfunction and ROS generation, which appeared to be mechanistically associated with translocation of K-ras to mitochondria and the opening of the mitochondrial permeability transition pore. K-ras induced mitochondrial dysfunction led to upregulation of glycolysis and constitutive activation of ROS-generating NAD(P)H Oxidase (NOX). Increased oxidative stress, upregulation of glycolytic activity, and constitutive activated NOX were also observed in the pancreatic K-ras transformed cancer cells compared to their normal counterparts. Compared to non-transformed cells, the pancreatic K-ras transformed cancer cells with activated NOX exhibited higher sensitivity to capsaicin, a natural compound that appeared to target NOX and cause preferential accumulation of oxidative stress in K-ras transformed cells. Taken together, these findings shed new light on the role played by Ras in the road to cancer in the context of oxidative stress and metabolic alteration. The mechanistic relationship between K-ras oncogenic signals and metabolic alteration in cancer will help to identify potential molecular targets such as NAD(P)H Oxidase and glycolytic pathway for therapeutic intervention of cancer development. ^

DEVELOPMENT AND IMPLEMENTATION OF A REMOTE AUDIT TOOL FOR HIGH DOSE RATE (HDR) 192IR BRACHYTHERAPY USING OPTICALLY STIMULATED LUMINESCENCE DOSIMETRY

This work aimed to create a mailable and OSLD-based phantom with accuracy suitable for RPC audits of HDR brachytherapy sources at institutions participating in NCI-funded cooperative clinical trials. An 8 × 8 × 10 cm3 prototype with two slots capable of holding nanoDot Al2O3:C OSL dosimeters (Landauer, Glenwood, IL) was designed and built. The phantom has a single channel capable of accepting all 192Ir HDR brachytherapy sources in current clinical use in the United States. Irradiations were performed with an 192Ir HDR source to determine correction factors for linearity with dose, dose rate, and the combined effect of irradiation energy and phantom construction. The uncertainties introduced by source positioning in the phantom and timer resolution limitations were also investigated. It was found that the linearity correction factor was where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters under 60Co irradiation. There was no significant dose rate effect. Separate energy+block correction factors were determined for both models of 192Ir sources currently in clinical use and these vendor-specific correction factors differed by almost 2.6%. For Nucletron sources, this correction factor was 1.026±0.004 (99% Confidence Interval) and for Varian sources it was 1.000±0.007 (99% CI). Reasonable deviations in source positioning within the phantom and the limited resolution of the source timer had insignificant effects on the ability to measure dose. Overall measurement uncertainty of the system was estimated to be ±2.5% for both Nucletron and Varian source audits (95% CI). This uncertainty was sufficient to establish a ±5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of eight participating institutions resulted in an average RPC-to-institution dose ratio of 1.000 with a standard deviation of 0.011.

Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

A STUDY ON THE FUNCTION OF 14-3-3SIGMA IN REGULATING CANCER ENERGY METABOLISM

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates c-Myc-induced metabolic target genes expression. Therefore, 14-3-3σ remarkably blocks glycolysis, decreases glutaminolysis and diminishes mitochondrial mass of cancer cells both in vitro and in vivo, thereby severely suppressing cancer bioenergetics and metabolism. As a result, a high level of 14-3-3σ in tumors is strongly associated with increased breast cancer patients’ overall and metastasis-free survival as well as better clinical outcomes. Thus, this study reveals a new role for 14-3-3s as a significant regulator of cancer bioenergetics and a promising target for the development of anti-cancer metabolism therapies.

Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.

Figures and related data of a review of the "Global and Russian energy outlook up to 2040"

The Global and Russian Energy Outlook up to 2040, prepared by the Energy Research Institute of the Russian Academy of Sciences and the Analytical Center for the Government of the Russian Federation, analyses the long-term changes in the main energy markets and thereby identifies the threats to the Russian economy and energy sector. Research has shown that shifts in the global energy sector, especially in hydrocarbon markets (primarily the development of technologies for shale oil and gas extraction), will result in a slowdown of Russia's economy by one percentage point each year on average due to a decrease in energy exports comparison with the official projections. Owing to the lack of development of an institutional framework, an outdated tax system, low competition and low investment efficiency, Russia will be the most sensitive to fluctuations in global hydrocarbon markets among all major energy market players within the forecast period.