Filopodia and stromal extracellular matrix as regulators of cancer cell invasion and growth

Bidirectional exchange of information between the cancer cells and their environment is essential for cancer to evolve. Cancer cells lose the ability to regulate their growth, gain the ability to detach from neighboring cells and finally some of the cells disseminate from the primary tumor and invade to the adjacent tissue. During cancer progression, cells acquire features that promote cancer motility and proliferation one of them being increased filopodia number. Filopodia are dynamic actin-rich structures extending from the leading edge of migrating cells and the main function of these structures is to serve as environmental sensors. It is nowadays widely appreciated, that not only the cancer cells, but also the surrounding of the tumor – the tumor microenvironment- contribute to cancer cell dissemination and tumor growth. Activated stromal fibroblasts, also known as cancer-associated fibroblasts (CAFs) actively participate on tumor progression. CAFs are the most abundant cell type surrounding the cancer cells and they are the main cell type producing the extracellular matrix (ECM) within tumor stroma. CAFs secrete growth factors to promote tumor growth, direct cancer cell invasion as well as modify the stromal ECM architecture. The aim of this thesis was to investigate the function of filopodia, particularly the role of filopodia-inducing protein Myosin-X (Myo10), in breast cancer cell invasion and metastasis. We found that Myo10 is an important regulator of basal type breast cancer spreading downstream of mutant p53. In addition, I investigated the role of CAFs and their secreted matrix on tumor growth. According to the results, CAF-derived matrix has altered organization and stiffness which induces the carcinoma cell proliferation via epigenetic mechanisms. I identified histone demethylase enzyme JMJD1a to be regulated by the stiffness and to participate in stiffness induced growth control.

Evaluation of the Efficiency of Line-Start Permanent-Magnet Machines as a Function of the Operating Temperature

The standard squirrel-cage induction machine has nearly reached its maximum efficiency. In order to further increase the energy efficiency of electrical machines, the use of permanent magnets in combination with the robust design and the line start capability of the induction machine is extensively investigated. Many experimental designs have been suggested in literature, but recently, these line-start permanent-magnet machines (LSPMMs) have become off-the-shelf products available in a power range up to 7.5 kW. The permanent magnet flux density is a function of the operating temperature. Consequently, the temperature will affect almost every electrical quantity of the machine, including current, torque, and efficiency. In this paper, the efficiency of an off-the-shelf 4-kW three-phase LSPMM is evaluated as a function of the temperature by both finite-element modeling and by practical measurements. In order to obtain stator, rotor, and permanent magnet temperatures, lumped thermal modeling is used.

Failure modes of passive decay heat removing safety systems of modern nuclear power plants

The purpose of this master’s thesis is to gain an understanding of passive safety systems’ role in modern nuclear reactors projects and to research the failure modes of passive decay heat removal safety systems which use phenomenon of natural circulation. Another purpose is to identify the main physical principles and phenomena which are used to establish passive safety tools in nuclear power plants. The work describes passive decay heat removal systems used in AES-2006 project and focuses on the behavior of SPOT PG system. The descriptions of the main large-scale research facilities of the passive safety systems of the AES-2006 power plant are also included. The work contains the calculations of the SPOT PG system, which was modeled with thermal-hydraulic system code TRACE. The dimensions of the calculation model are set according to the dimensions of the real SPOT PG system. In these calculations three parameters are investigated as a function of decay heat power: the pressure of the system, the natural circulation mass flow rate around the closed loop, and the level of liquid in the downcomer. The purpose of the calculations is to test the ability of the SPOT PG system to remove the decay heat from the primary side of the nuclear reactor in case of failure of one, two, or three loops out of four. The calculations show that three loops of the SPOT PG system have adequate capacity to provide the necessary level of safety. In conclusion, the work supports the view that passive systems could be widely spread in modern nuclear projects.

"I like my beer cold, my TV loud, and my homosexuals flaming!" : preference for stereotype consistency as a function of a person x situation interaction /

The study centers on the power of Right-Wing Authoritarianism (RWA) and Social Dominance Orientation (SDO) as predictors of prejudice against stereotypical and nonstereotypical homosexuals under the threat of death and the threat of uncertainty. Right-wing authoritarianism (RWA) is an individual difference variable that measures the tendency for individuals to unquestionably follow those perceived to be authorities. Social Dominance Orientation (SDO) is an individual difference variable that measures the degree to which an individual prefers inequality among social groups. The RWA and SDO Scales are considered to be two of the strongest predictors of prejudice, such as prejudice against homosexuals. The study focuses on the unique predictive power of these two variables in predicting prejudice against homosexuals. The study also examines the role of situational threat in prejudice, specifically the threat of death (mortality salience) and the threat of uncertainty (uncertainty salience). Competing predictions from theories involving the threat of death (Terror Management Theory) and the threat of uncertainty (Uncertainty Management Theory) are also tested. The preference for expected information in the form of stereotypes concerning male homosexuals (that is, a stereotypical or non-stereotypical homosexual) were tested. The difference between the predictive power ofRWA and SDO was examined by measuring how these variables predict liking of a stereotypical or non-stereotypical homosexual under the threat of death, the threat of uncertainty, or a control condition. Along with completing a measure for RWA and a measure for SDO, participants were asked to think of their own death, of their being uncertain or about watching television then were asked to read about a week in the life of either a stereotypical or non-stereotypical male homosexual. Participants were then asked to evaluate the individual and his essay. Based on the participants' evaluations, results from 180 heterosexual university students show that RWA and SDO are strong predictors for disliking of a stereotypical homosexual under the threat of uncertainty and disliking of a non-stereotypical homosexual under the threat of death. Furthermore, however, results show that RWA is a particularly strong predictor of disliking of a stereotypical homosexual under the threat of uncertainty, whereas SDO is an exceptionally strong predictor of disliking of the non-stereotypical homosexual under the threat of death. This further adds to the notion that RWA and SDO are indeed unique predictors of prejudice. Implications are also explored, including the fact that the study simuhaneously examined the role of individual difference variables and situational threat variables, as well as exploratory analysis on Dominating Authoritarians.

Expression and function of endothelin and its receptors in vascular adventitial fibroblasts

Objective: The adventitia has been recognized to play important roles in vascular oxidative stress, remodelling and contraction. We recently demonstrated that adventitial fibroblasts are able to express endothelin-1 (ET-1) in response to angiotensin II (ANG II). However, the mechanisms by which ANG II induces ET-1 expression are unknown. It is also unclear whether the ET-1 receptors are expressed in the adventitia. We therefore examined the role of oxidative stress in the regulation of ET-1. We also investigated the expression of both the ETA and ETB receptors and the roles of these two types of receptors in collagen synthesis and ET-1 clearance in adventitial fibroblasts. Methods and Results: Adventitial fibroblasts were isolated and cultured from the thoracic mouse aorta. Cells were treated with ANG II (lOOnM), ET-1 (lOpM), NADPH oxidase inhibitor apocynin (lOOfiM), the superoxide anion scavenger tempol (lOOfiM), the ANG II receptor antagonists (100[aM), losartan (AT| receptor) and PD 1233 19 (AT2 receptor), the ET-1 receptor antagonists (lOOuM), BQ123 (ETA receptor) and BQ788 (ETB receptor), and the ETB receptor agonist (lOOnM) Sarafotoxin 6C. ET-1 peptide levels were determined by ELISA, while ETA ,ETB and collagen levels were determined by Western blot. ANG II increased ET-1 peptide levels in a time-dependent manner reaching significance when incubated for 24 hours. NAD(P)H oxidase inhibitor, apocynin, as well as the superoxide scanverger, tempol, significantly reduced ANG Il-induced ET-1 peptide levels while over-expression of SOD1 (endogenous antioxidant enzyme) significantly decreased ANG Il-induced collagen I expression, therefore implicating reactive oxygen species in the mediation of ET-1. ANG II increased ETA receptor protein as well as collagen in a similar fashion, reaching significance after 4, 6, and 24 hours treatment. ANG II induced collagen was reduced while in the presence of the ETA receptor antagonist suggesting the role of the ETa receptor in the regulation of the extracellular matrix. ANG II treatment also increased ETB receptor protein levels in a time-dependent manner. ANG II treatment in the presence of the ETB receptor antagonist significantly increased ET-1 peptide levels. On another hand, the ETB receptor agonist, Sarafotoxin 6C, significantly decreased ET-1 peptide levels. These data implicate the role of the ETb receptor in the clearance of the ET-1 peptide. Conclusion: ANG II-induced increases of ET-1 peptide appears to be mediated by reactive oxygen species derived from NAD(P)H oxidase. Both the ETA and ETB receptors are expressed in adventitial fibroblasts. The ETA receptor subtype mediates collagen I expression, while the ETB receptor may play a protective role through increasing the clearance of the ET- 1 peptide.

The role of daytime napping in sleepiness and cognitive function in 24-70 year olds /

Daytime napping improves well-being and performance for young adults. The benefits of napping in older adults should be investigated because they have fragmented nocturnal sleep, cognitive declines, and more opportunity to nap. In addition, experience with napping might influence the benefits of napping. Study 1 examined the role of experience with napping in young adults. Habitual (n = 23) and non-habitual nappers (n = 16) were randomly assigned to a 20-minute nap or a 20- minute reading condition. Both groups slept the same according to macro architecture. However, microarchitecture showed greater theta, alpha, and beta power during Stage 1, and greater delta, alpha, and sigma power during Stage 2 for habitual nappers, for the most part indicating better sleep. Both groups felt less sleepy after the nap. P2 latency, reflecting information processing, decreased after the nap for habitual nappers, and after the control condition for non-habitual nappers. In sum, both groups who slept felt better, but only the habitual nappers who napped gained a benefit in terms of information processing. Based on this outcome, experience with napping was investigated in Study 2. Study 2 examined the extent to which daytime napping enhanced cognition in older adults, especially frontal lobe function. Cognitive deficits in older adults may be due to sleep loss and age-related decline in brain functioning. Longer naps were expected to provide greater improvement, particularly for older adults, by reducing sleep pressure. Thirty-two adults, aged 24-70 years, participated in a repeated measures dose-response manipulation of sleep pressure. Twenty- and sixty-minute naps were compared to a no-nap condition in three age groups. Mood, subjective sleepiness, reaction time, working memory, 11 novelty detection, and waking electro physiological measures were taken before and after each condition. EEG was also recorded during each nap or rest condition. Napping reduced subjective sleepiness, improved working memory (serial addition / subtraction task), and improved attention (reduced P2 amplitude). Physiological sleepiness (i.e., waking theta power) increased following the control condition, and decreased after the longer nap. Increased beta power after the short nap, and seen with older adults overall, may have reflected increased mental effort. Older adults had longer latencies and smaller amplitudes for several event-related potential components, and higher beta and gamma power. Following the longer nap, gamma power decreased for older adults, but increased for young adults. Beta and gamma power may represent enhanced alertness or mental effort. In addition, Nl amplitude showed that benefits depend on the preceding nap length as well as age. Since the middle group had smaller Nl amplitudes following the short nap and rest condition, it is possible that they needed a longer nap to maintain alertness. Older adults did not show improvements to Nl amplitude following any condition; they may have needed a nap longer than 60 minutes to gain benefits to attention or early information processing. Sleep characteristics were not related to benefits of napping. Experience with napping was also investigated. Subjective data confirmed habitual nappers were happier to nap, while non-habitual nappers were happier to stay awake, reflecting self-identified napping habits. Non-habitual nappers were sleepier after a nap, and had faster brain activity (i.e., heightened vigilance) at sleep onset. These reasons may explain why non-habitual nappers choose not to nap.

A Foucaultian analysis of power relations in child protection case work with youth and families

This thesis takes some steps in examining the child protection system from a position that is rarely discussed. Specifically, I explore how Foucault's concept of disciplinary power can be used to demonstrate how power operates within the client/worker relationship. This relationship is shown to be quite complex with power flowing bidirectionally, rather than hierarchically. Instead of viewing power imbalances as a function of state control, I show how the client/worker relationship is constituted by the worker, the client, the organization and the social body. A postmodern auto ethnography is used to document my journey as I expose the disciplinary practices and instruments that I was subject to and used with my clients. 2 Given that the child protection system is constantly shifting and changing in order to improve its ability to safeguard children a greater emphasis is required to examine how workers operate within this complex, overwhelming and multi-dimensional world. This thesis has shown that by engaging in a reflexive examination of my position of power different approaches to making intervention beneficial to all involved become available. This is important if child protection work aims to work with clients rather than on clients.

THE INFLUENCE OF LENGTH CHANGE SPEED AND DIRECTION ON DYNAMIC FUNCTION POTENTIATION IN FAST MOUSE MUSCLE

The purpose of this study was to test the hypothesis that the potentiation of dynamic function was dependent upon both length change speed and direction. Mouse EDL was cycled in vitro (25º C) about optimal length (Lo) with constant peak strain (± 2.5% Lo) at 1.5, 3.3 and 6.9 Hz before and after a conditioning stimulus. A single pulse was applied during shortening or lengthening and peak dynamic (concentric or eccentric) forces were assessed at Lo. Stimulation increased peak concentric force at all frequencies (range: 19 ± 1 to 30 ± 2%) but this increase was proportional to shortening speed, as were the related changes to concentric work/power (range: -15 ± 1 to 39 ± 1 %). In contrast, stimulation did not increase eccentric force, work or power at any frequency. Thus, results reveal a unique hysteresis like effect for the potentiation of dynamic output wherein concentric and eccentric forces increase and decrease, respectively, with work cycle frequency.

THE INFLUENCE OF LENGTH CHANGE SPEED AND DIRECTION ON DYNAMIC FUNCTION POTENTIATION IN FAST MOUSE MUSCLE

The purpose of this study was to test the hypothesis that the potentiation of dynamic function was dependent upon both length change speed and direction. Mouse EDL was cycled in vitro (250 C) about optimal length (Lo) with constant peak strain (± 2.5% Lo) at 1.5,3.3 and 6.9 Hz before and after a conditioning stimulus. A single pulse was applied during shortening or lengthening and peak dynamic (concentric or eccentric) forces were assessed at Lo. Stimulation increased peak concentric force at all frequencies (range: 19±1 to 30 ± 2%) but this increase was proportional to shortening speed, as were the related changes to concentric work/power (range: -15 ± 1 to 39 ± 1 %). In contrast, stimulation did not increase eccentric force, work or power at any frequency. Thus, results reveal a unique hysteresis like effect for the potentiation of dynamic output wherein concentric and eccentric forces increase and decrease, respectively, with work cycle frequency.

Effects of Plyometric and Resistance Training on Muscle Strength and Neuromuscular Function in Young Adolescent Soccer Players

This study examined the effect of 8-weeks of resistance (RT) and plyometric (PLYO) training on maximal strength, power and jump performance compared with no added training (CON), in young male soccer players. Forty-one 11-13 year-old soccer players were divided into three groups (RT, PLYO, CON). All participants completed 5 isometric knee extensions at 90° and 5 isokinetic knee extensions at 240°/s pre- and post-training. Peak torque (PT), peak rate of torque development (pRTD), electromechanical-day (EMD), rate of muscle activation (Q30), muscle cross-sectional area (mCSA) and jump performance were examined. Both RT and PLYO resulted in significant (p < 0.05) increases in PT, pRTD and jump performance. RT resulted in significantly greater increases in both isometric and isokinetic PT, while PLYO resulted in significantly greater increases in isometric pRTD and jump performance compared with CON (p < 0.05). Q30 increased to a greater extent in PLYO (20%) compared with RT (5%) and CON (-5%) (p = 0.1). In conclusion, 8-weeks of RT and PLYO resulted in significant improvements in muscle strength and jump performance. RT appears to be more effective at eliciting increases in maximal strength while PLYO appears to enhance explosive strength, mediated by possible increases in the rate of muscle activation.

The Seemingly Unrelated Dynamic Cointegration Regression Model and Testing for Purching Power Parity.

This paper studies seemingly unrelated linear models with integrated regressors and stationary errors. By adding leads and lags of the first differences of the regressors and estimating this augmented dynamic regression model by feasible generalized least squares using the long-run covariance matrix, we obtain an efficient estimator of the cointegrating vector that has a limiting mixed normal distribution. Simulation results suggest that this new estimator compares favorably with others already proposed in the literature. We apply these new estimators to the testing of purchasing power parity (PPP) among the G-7 countries. The test based on the efficient estimates rejects the PPP hypothesis for most countries.

Non-negative matrix decomposition approaches to frequency domain analysis of music audio signals

On étudie l’application des algorithmes de décomposition matricielles tel que la Factorisation Matricielle Non-négative (FMN), aux représentations fréquentielles de signaux audio musicaux. Ces algorithmes, dirigés par une fonction d’erreur de reconstruction, apprennent un ensemble de fonctions de base et un ensemble de coef- ficients correspondants qui approximent le signal d’entrée. On compare l’utilisation de trois fonctions d’erreur de reconstruction quand la FMN est appliquée à des gammes monophoniques et harmonisées: moindre carré, divergence Kullback-Leibler, et une mesure de divergence dépendente de la phase, introduite récemment. Des nouvelles méthodes pour interpréter les décompositions résultantes sont présentées et sont comparées aux méthodes utilisées précédemment qui nécessitent des connaissances du domaine acoustique. Finalement, on analyse la capacité de généralisation des fonctions de bases apprises par rapport à trois paramètres musicaux: l’amplitude, la durée et le type d’instrument. Pour ce faire, on introduit deux algorithmes d’étiquetage des fonctions de bases qui performent mieux que l’approche précédente dans la majorité de nos tests, la tâche d’instrument avec audio monophonique étant la seule exception importante.

Photosensitivity of Laser Dye Mixtures in Polymer Matrix – A Photoacoustic Study

Laser induced photoacoustic (PA) technique is used in the study of photostability of polymethyl methacrylate (PMMA) films doped with Rhodamine 6G -Rhodamine B dye system. Energy transfer from a donor molecule to an acceptor molecule in a dye mixture affects the output of the dye system. Details of investigations on the role of laser power, modulation frequency and the irradiation wavelength on the photosensitivity of the dye mixture doped PMMA films are presented.

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Semiclassical evaluation of average nuclear one- and two-body matrix elements

Thomas-Fermi theory is developed to evaluate nuclear matrix elements averaged on the energy shell, on the basis of independent particle Hamiltonians. One- and two-body matrix elements are compared with the quantal results, and it is demonstrated that the semiclassical matrix elements, as function of energy, well pass through the average of the scattered quantum values. For the one-body matrix elements it is shown how the Thomas-Fermi approach can be projected on good parity and also on good angular momentum. For the two-body case, the pairing matrix elements are considered explicitly.