Development of a measuring-control system for energy monitoring in low power

In this thesis a control system for an intelligent low voltage energy grid is presented, focusing on the control system created by using a multi-agent approach which makes it versatile and easy to expand according to the future needs. The control system is capable of forecasting the future energy consumption and decisions making on its own without human interaction when countering problems. The control system is a part of the St. Petersburg State Polytechnic University’s smart grid project that aims to create a smart grid for the university’s own use. The concept of the smart grid is interesting also for the consumers as it brings new possibilities to control own energy consumption and to save money. Smart grids makes it possible to monitor the energy consumption in real-time and to change own habits to save money. The intelligent grid also brings possibilities to integrate the renewable energy sources to the global or the local energy production much better than the current systems. Consumers can also sell their extra power to the global grid if they want.

The knapsack problem approach in solving partial hedging problems of options

En option är ett finansiellt kontrakt som ger dess innehavare en rättighet (men medför ingen skyldighet) att sälja eller köpa någonting (till exempel en aktie) till eller från säljaren av optionen till ett visst pris vid en bestämd tidpunkt i framtiden. Den som säljer optionen binder sig till att gå med på denna framtida transaktion ifall optionsinnehavaren längre fram bestämmer sig för att inlösa optionen. Säljaren av optionen åtar sig alltså en risk av att den framtida transaktion som optionsinnehavaren kan tvinga honom att göra visar sig vara ofördelaktig för honom. Frågan om hur säljaren kan skydda sig mot denna risk leder till intressanta optimeringsproblem, där målet är att hitta en optimal skyddsstrategi under vissa givna villkor. Sådana optimeringsproblem har studerats mycket inom finansiell matematik. Avhandlingen "The knapsack problem approach in solving partial hedging problems of options" inför en ytterligare synpunkt till denna diskussion: I en relativt enkel (ändlig och komplett) marknadsmodell kan nämligen vissa partiella skyddsproblem beskrivas som så kallade kappsäcksproblem. De sistnämnda är välkända inom en gren av matematik som heter operationsanalys. I avhandlingen visas hur skyddsproblem som tidigare lösts på andra sätt kan alternativt lösas med hjälp av metoder som utvecklats för kappsäcksproblem. Förfarandet tillämpas även på helt nya skyddsproblem i samband med så kallade amerikanska optioner.

Improving product profitability control in continuous IT-services

The target of the thesis is to improve product profitability control in continuous IT-services. Accurate product cost accounting and correctly allocated revenues are a necessity for good product profitability control. The focus of the study is on costs and revenues that are not traced directly to services. The thesis is focused on revenue allocations as revenue allocation methods have not been used in the case company before. In order to achieve the target revenue allocation methods, which improve the product profitability accounting and control, are presented. The research methods used in the thesis are literature review and empirical case study. The research approach is constructive. The theoretical part is composed of literature and articles that create a base for the empirical part. Internal interviews describe the current situation in the company and based on it development actions are planned. The part of the empirical case study is seen mostly in the limitations as the research is limited to concern only one department in the company. Problems in the revenue tracing are caused by customer specific services and lack of service definitions because of which the revenues are not traced correctly. Methods to allocate revenues are presented in the thesis and stand-alone revenue allocation method is the most suitable one because it is fair and it can be modified. Approximate product profitability analysis is done in the thesis and the results of it indicate that some services are profitable and some unprofitable.

Management practices to control gastrointestinal parasites in sheep farms in Minas Gerais, southeastern Brazil

Parasite related problems are considered one of the major health problems for sheep breeding, causing considerable economic losses to commercial husbandry. The aim of this study was to determine the technological level and the level of knowledge of farmers regarding management practices to control gastrointestinal parasites in sheep in Minas Gerais state, southeastern Brazil. The analysis was based on 213 questionnaires applied by official veterinarians of the State Government Agency for Animal Health (Instituto Mineiro de Agropecuária, IMA), covering 16.6% of all counties. From two hundred and thirteen sheep farms sampled, 117 farms had their technological level determined. From the samples, 0.9% were characterized as high level, 45.3% as medium, and 53.0% as low technological level. The flock size ranged from 2 to 1843 with an average of 80.5 sheep per farm. The majority of the sheep production systems was extensive/semi-extensive (74.5%). The management practices adopted by the farmers to reduce parasitism were: split young and adult animals (5.6%), change pasture after deworm the animals (5.2%), use quarantine for incoming animals (2.3%), deworm newly arrived sheep (1.5%), and have regular technical assistance (31.9%). Although 76.5% of the farmers medicate the animals, treatments were performed without any major technical criteria, with an average interval of 4.6 months. The most commonly used drug families were macrocyclic lactones (38.5%) and benzimidazoles (24.9%). The management practices adopted in Minas Gerais are based on old recommendations and may not return in a good set of strategies to prevent parasite infections. Field observations reinforce the finding where farmers have obtained unsatisfactory results in maintaining the health and productivity level of their enterprises.

Nonlinear dynamics and control of multibody systems

The dynamics of flexible systems, such as robot manipulators , mechanical chains or multibody systems in general, is becoming increasingly important in engineering. This article deals with some nonlinearities that arise in the study of dynamics and control of multibody systems in connection to large rotations. Specifically, a numerical scheme that adresses the conservation of fundamental constants is presented in order to analyse the control-structure interaction problems.

Planting density of gliricidia when intercropped with corn for weed control

Reduced use of herbicides that cause environmental pollution problems is of great interest in modern agriculture. Soil mulching with gliricidia (Gliricidia sepium) branches does not have an allelopathic effect on corn, but decreases weed populations. The objective of this study was to evaluate the effects of gliricidia planting density, when grown as an intercrop, on weed control and corn yield parameters. A randomized block design with split-plots and ten replicates was adopted. Corn cultivars AG 1051 and BM 3061 were grown without hoeing, with two hoes (at 24 and 44 days after planting), and intercropped with gliricidia (planted simultaneously with corn, between crop rows, using two seedlings/pit, spaced at 30, 40, or 50 cm). Twenty-one weed species were found in the experimental area. Increased gliricidia planting density reduced weed biomass, but no difference was found between weed biomass in the intercrop and weed biomass in non-hoed corn. Gliricidia intercropped with corn, planted at a row spacing of 30 cm, did not significantly differ from hoed corn in most characteristics considered to evaluate green corn yield, although mean values were smaller. As to the number and weight of marketable green ears, reductions of 5% and 13%, respectively, were observed. Intercropping caused a 17% reduction in grain yield, reducing the losses (36%) observed in non-hoed corn by more than 50%. The highest green ear yield and grain yield values were obtained with two hoeings, while the lowest values were observed for non-hoed corn. The cultivars did not differ regarding green ear yield and grain yield.

Weed control in corn via intercropping with gliricidia sown by broadcasting

There has been interest in reducing the use of herbicides for weed control in order to decrease environmental degradation problems. The objective of this study was to evaluate the effects of gliricidia planting density sown by broadcasting and intercopping on green ear and corn grain yield as well as on weed control. A randomized block design with split-plots and five replicates were adopted. Cultivars AG 1051, BM 2022, and BM 3061, assigned to plots, were submitted to the following treatments: no hoeing, two hoeings (at 20 and 40 days after sowing), and intercropped with gliricidia sown at densities of 10 and 20 seeds m-2. Thirty weed species occurred in the experiment area, with Cucumis anguria as the most frequent ones. Cultivar BM 2022 was the best for the total number of ears (TNE) and number (NMHE) and weight of marketable husked ears. Together with cultivar AG 1051, this cultivar had the highest total weight and marketable unhusked ear weight (MUEW). However, the cultivars did not differ with respect to grain yield (GY). The highest green ear and corn grain yield and weed control percentages were obtained with two hoeings; in MUEW, NMHE and GY, intercropping provided intermediate means in comparison with those obtained in hoed and non-hoed plots, indicating that gliricidia was partially beneficial to corn. Increased gliricidia seeding density heightened the benefits to corn (TNE and MUEW). The lack of hoeing produced the poorest green ear and grain yields.

Excessive functions, Appell polynomials and optimal stopping

The main topic of the thesis is optimal stopping. This is treated in two research articles. In the first article we introduce a new approach to optimal stopping of general strong Markov processes. The approach is based on the representation of excessive functions as expected suprema. We present a variety of examples, in particular, the Novikov-Shiryaev problem for Lévy processes. In the second article on optimal stopping we focus on differentiability of excessive functions of diffusions and apply these results to study the validity of the principle of smooth fit. As an example we discuss optimal stopping of sticky Brownian motion. The third research article offers a survey like discussion on Appell polynomials. The crucial role of Appell polynomials in optimal stopping of Lévy processes was noticed by Novikov and Shiryaev. They described the optimal rule in a large class of problems via these polynomials. We exploit the probabilistic approach to Appell polynomials and show that many classical results are obtained with ease in this framework. In the fourth article we derive a new relationship between the generalized Bernoulli polynomials and the generalized Euler polynomials.

Flexible multibody dynamics and intelligent control of a hydraulically driven hybrid redundant robot machine

The assembly and maintenance of the International Thermonuclear Experimental Reactor (ITER) vacuum vessel (VV) is highly challenging since the tasks performed by the robot involve welding, material handling, and machine cutting from inside the VV. The VV is made of stainless steel, which has poor machinability and tends to work harden very rapidly, and all the machining operations need to be carried out from inside of the ITER VV. A general industrial robot cannot be used due to its poor stiffness in the heavy duty machining process, and this will cause many problems, such as poor surface quality, tool damage, low accuracy. Therefore, one of the most suitable options should be a light weight mobile robot which is able to move around inside of the VV and perform different machining tasks by replacing different cutting tools. Reducing the mass of the robot manipulators offers many advantages: reduced material costs, reduced power consumption, the possibility of using smaller actuators, and a higher payload-to-robot weight ratio. Offsetting these advantages, the lighter weight robot is more flexible, which makes it more difficult to control. To achieve good machining surface quality, the tracking of the end effector must be accurate, and an accurate model for a more flexible robot must be constructed. This thesis studies the dynamics and control of a 10 degree-of-freedom (DOF) redundant hybrid robot (4-DOF serial mechanism and 6-DOF 6-UPS hexapod parallel mechanisms) hydraulically driven with flexible rods under the influence of machining forces. Firstly, the flexibility of the bodies is described using the floating frame of reference method (FFRF). A finite element model (FEM) provided the Craig-Bampton (CB) modes needed for the FFRF. A dynamic model of the system of six closed loop mechanisms was assembled using the constrained Lagrange equations and the Lagrange multiplier method. Subsequently, the reaction forces between the parallel and serial parts were used to study the dynamics of the serial robot. A PID control based on position predictions was implemented independently to control the hydraulic cylinders of the robot. Secondly, in machining, to achieve greater end effector trajectory tracking accuracy for surface quality, a robust control of the actuators for the flexible link has to be deduced. This thesis investigates the intelligent control of a hydraulically driven parallel robot part based on the dynamic model and two schemes of intelligent control for a hydraulically driven parallel mechanism based on the dynamic model: (1) a fuzzy-PID self-tuning controller composed of the conventional PID control and with fuzzy logic, and (2) adaptive neuro-fuzzy inference system-PID (ANFIS-PID) self-tuning of the gains of the PID controller, which are implemented independently to control each hydraulic cylinder of the parallel mechanism based on rod length predictions. The serial component of the hybrid robot can be analyzed using the equilibrium of reaction forces at the universal joint connections of the hexa-element. To achieve precise positional control of the end effector for maximum precision machining, the hydraulic cylinder should be controlled to hold the hexa-element. Thirdly, a finite element approach of multibody systems using the Special Euclidean group SE(3) framework is presented for a parallel mechanism with flexible piston rods under the influence of machining forces. The flexibility of the bodies is described using the nonlinear interpolation method with an exponential map. The equations of motion take the form of a differential algebraic equation on a Lie group, which is solved using a Lie group time integration scheme. The method relies on the local description of motions, so that it provides a singularity-free formulation, and no parameterization of the nodal variables needs to be introduced. The flexible slider constraint is formulated using a Lie group and used for modeling a flexible rod sliding inside a cylinder. The dynamic model of the system of six closed loop mechanisms was assembled using Hamilton’s principle and the Lagrange multiplier method. A linearized hydraulic control system based on rod length predictions was implemented independently to control the hydraulic cylinders. Consequently, the results of the simulations demonstrating the behavior of the robot machine are presented for each case study. In conclusion, this thesis studies the dynamic analysis of a special hybrid (serialparallel) robot for the above-mentioned special task involving the ITER and investigates different control algorithms that can significantly improve machining performance. These analyses and results provide valuable insight into the design and control of the parallel robot with flexible rods.

Weed control in corn and weed sample size for growth evaluations

The objectives of this study were to evaluate baby corn yield, green corn yield, and grain yield in corn cultivar BM 3061, with weed control achieved via a combination of hoeing and intercropping with gliricidia, and determine how sample size influences weed growth evaluation accuracy. A randomized block design with ten replicates was used. The cultivar was submitted to the following treatments: A = hoeings at 20 and 40 days after corn sowing (DACS), B = hoeing at 20 DACS + gliricidia sowing after hoeing, C = gliricidia sowing together with corn sowing + hoeing at 40 DACS, D = gliricidia sowing together with corn sowing, and E = no hoeing. Gliricidia was sown at a density of 30 viable seeds m-2. After harvesting the mature ears, the area of each plot was divided into eight sampling units measuring 1.2 m² each to evaluate weed growth (above-ground dry biomass). Treatment A provided the highest baby corn, green corn, and grain yields. Treatment B did not differ from treatment A with respect to the yield values for the three products, and was equivalent to treatment C for green corn yield, but was superior to C with regard to baby corn weight and grain yield. Treatments D and E provided similar yields and were inferior to the other treatments. Therefore, treatment B is a promising one. The relation between coefficient of experimental variation (CV) and sample size (S) to evaluate growth of the above-ground part of the weeds was given by the equation CV = 37.57 S-0.15, i.e., CV decreased as S increased. The optimal sample size indicated by this equation was 4.3 m².

Public-private partnership investments in dry ports – Russian logistics markets and risks

The investments have always been considered as an essential backbone and so-called ‘locomotive’ for the competitive economies. However, in various countries, the state has been put under tight budget constraints for the investments in capital intensive projects. In response to this situation, the cooperation between public and private sector has grown based on public-private mechanism. The promotion of favorable arrangement for collaboration between public and private sectors for the provision of policies, services, and infrastructure in Russia can help to address the problems of dry ports development that neither municipalities nor the private sector can solve alone. Especially, the stimulation of public-private collaboration is significant under the exposure to externalities that affect the magnitude of the risks during all phases of project realization. In these circumstances, the risk in the projects also is becoming increasingly a part of joint research and risk management practice, which is viewed as a key approach, aiming to take active actions on existing global and specific factors of uncertainties. Meanwhile, a relatively little progress has been made on the inclusion of the resilience aspects into the planning process of a dry ports construction that would instruct the capacity planner, on how to mitigate the occurrence of disruptions that may lead to million dollars of losses due to the deviation of the future cash flows from the expected financial flows on the project. The current experience shows that the existing methodological base is developed fragmentary within separate steps of supply chain risk management (SCRM) processes: risk identification, risk evaluation, risk mitigation, risk monitoring and control phases. The lack of the systematic approach hinders the solution of the problem of risk management processes of dry port implementation. Therefore, management of various risks during the investments phases of dry port projects still presents a considerable challenge from the practical and theoretical points of view. In this regard, the given research became a logical continuation of fundamental research, existing in the financial models and theories (e.g., capital asset pricing model and real option theory), as well as provided a complementation for the portfolio theory. The goal of the current study is in the design of methods and models for the facilitation of dry port implementation through the mechanism of public-private partnership on the national market that implies the necessity to mitigate, first and foremost, the shortage of the investments and consequences of risks. The problem of the research was formulated on the ground of the identified contradictions. They rose as a continuation of the trade-off between the opportunities that the investors can gain from the development of terminal business in Russia (i.e. dry port implementation) and risks. As a rule, the higher the investment risk, the greater should be their expected return. However, investors have a different tolerance for the risks. That is why it would be advisable to find an optimum investment. In the given study, the optimum relates to the search for the efficient portfolio, which can provide satisfaction to the investor, depending on its degree of risk aversion. There are many theories and methods in finance, concerning investment choices. Nevertheless, the appropriateness and effectiveness of particular methods should be considered with the allowance of the specifics of the investment projects. For example, the investments in dry ports imply not only the lump sum of financial inflows, but also the long-term payback periods. As a result, capital intensity and longevity of their construction determine the necessity from investors to ensure the return on investment (profitability), along with the rapid return on investment (liquidity), without precluding the fact that the stochastic nature of the project environment is hardly described by the formula-based approach. The current theoretical base for the economic appraisals of the dry port projects more often perceives net present value (NPV) as a technique superior to other decision-making criteria. For example, the portfolio theory, which considers different risk preference of an investor and structures of utility, defines net present value as a better criterion of project appraisal than discounted payback period (DPP). Meanwhile, in business practice, the DPP is more popular. Knowing that the NPV is based on the assumptions of certainty of project life, it cannot be an accurate appraisal approach alone to determine whether or not the project should be accepted for the approval in the environment that is not without of uncertainties. In order to reflect the period or the project’s useful life that is exposed to risks due to changes in political, operational, and financial factors, the second capital budgeting criterion – discounted payback period is profoundly important, particularly for the Russian environment. Those statements represent contradictions that exist in the theory and practice of the applied science. Therefore, it would be desirable to relax the assumptions of portfolio theory and regard DPP as not fewer relevant appraisal approach for the assessment of the investment and risk measure. At the same time, the rationality of the use of both project performance criteria depends on the methods and models, with the help of which these appraisal approaches are calculated in feasibility studies. The deterministic methods cannot ensure the required precision of the results, while the stochastic models guarantee the sufficient level of the accuracy and reliability of the obtained results, providing that the risks are properly identified, evaluated, and mitigated. Otherwise, the project performance indicators may not be confirmed during the phase of project realization. For instance, the economic and political instability can result in the undoing of hard-earned gains, leading to the need for the attraction of the additional finances for the project. The sources of the alternative investments, as well as supportive mitigation strategies, can be studied during the initial phases of project development. During this period, the effectiveness of the investments undertakings can also be improved by the inclusion of the various investors, e.g. Russian Railways’ enterprises and other private companies in the dry port projects. However, the evaluation of the effectiveness of the participation of different investors in the project lack the methods and models that would permit doing the particular feasibility study, foreseeing the quantitative characteristics of risks and their mitigation strategies, which can meet the tolerance of the investors to the risks. For this reason, the research proposes a combination of Monte Carlo method, discounted cash flow technique, the theory of real options, and portfolio theory via a system dynamics simulation approach. The use of this methodology allows for comprehensive risk management process of dry port development to cover all aspects of risk identification, risk evaluation, risk mitigation, risk monitoring, and control phases. A designed system dynamics model can be recommended for the decision-makers on the dry port projects that are financed via a public-private partnership. It permits investors to make a decision appraisal based on random variables of net present value and discounted payback period, depending on different risks factors, e.g. revenue risks, land acquisition risks, traffic volume risks, construction hazards, and political risks. In this case, the statistical mean is used for the explication of the expected value of the DPP and NPV; the standard deviation is proposed as a characteristic of risks, while the elasticity coefficient is applied for rating of risks. Additionally, the risk of failure of project investments and guaranteed recoupment of capital investment can be considered with the help of the model. On the whole, the application of these modern methods of simulation creates preconditions for the controlling of the process of dry port development, i.e. making managerial changes and identifying the most stable parameters that contribute to the optimal alternative scenarios of the project realization in the uncertain environment. System dynamics model allows analyzing the interactions in the most complex mechanism of risk management process of the dry ports development and making proposals for the improvement of the effectiveness of the investments via an estimation of different risk management strategies. For the comparison and ranking of these alternatives in their order of preference to the investor, the proposed indicators of the efficiency of the investments, concerning the NPV, DPP, and coefficient of variation, can be used. Thus, rational investors, who averse to taking increased risks unless they are compensated by the commensurate increase in the expected utility of a risky prospect of dry port development, can be guided by the deduced marginal utility of investments. It is computed on the ground of the results from the system dynamics model. In conclusion, the outlined theoretical and practical implications for the management of risks, which are the key characteristics of public-private partnerships, can help analysts and planning managers in budget decision-making, substantially alleviating the effect from various risks and avoiding unnecessary cost overruns in dry port projects.

Development of a New Welding Product Quality Control and Management System Model for China

The Chinese welding industry is growing every year due to rapid development of the Chinese economy. Increasingly, companies around the world are looking to use Chinese enterprises as their cooperation partners. However, the Chinese welding industry also has its weaknesses, such as relatively low quality and weak management. A modern, advanced welding management system appropriate for local socio-economic conditions is required to enable Chinese enterprises to enhance further their business development. The thesis researches the design and implementation of a new welding quality management system for China. This new system is called ‗welding production quality control management model in China‘ (WQMC). Constructed on the basis of analysis of a survey and in-company interviews, the welding management system comprises the following different elements and perspectives: a ‗Localized congenital existing problem resolution strategies‘ (LCEPRS) database, a ‗human factor designed training system‘ (HFDT) training strategy, the theory of modular design, ISO 3834 requirements, total welding management (TWM), and lean manufacturing (LEAN) theory. The methods used in the research are literature review, questionnaires, interviews, and the author‘s model design experiences and observations, i.e. the approach is primarily qualitative and phenomenological. The thesis describes the design and implementation of a HFDT strategy in Chinese welding companies. Such training is an effective way to increase employees‘ awareness of quality and issues associated with quality assurance. The study identified widely existing problems in the Chinese welding industry and constructed a LCEPRS database that can be used in efforts to mitigate and avoid common problems. The work uses the theory of modular design, TWM and LEAN as tools for the implementation of the WQMC system.

Predictors of academic achievement and social competence in adolescence : facilitation, inhibition and general cognitive processing /

The relevance of attentional measures to cognitive and social adaptive behaviour was examined in an adolescent sample. Unlike previous research, the influence of both inhibitory and facilitory aspects of attention were studied. In addition, contributions made by these attentional processes were compared with traditional psychometric measures of cognitive functioning. Data were gathered from 36 grade 10 and 1 1 high school students (20 male and 16 female students) with a variety of learning and attentional difficulties. Data collection was conducted in the course of two testing sessions. In the first session, students completed questionnaires regarding their medical history, and everyday behaviours (the Brock Adaptive Functioning Questionnaire), along with non-verbal problem solving tasks and motor speed tasks. In the second session, students performed working memory measures and computer-administered tasks assessing inhibitory and facilitory aspects of attention. Grades and teacher-rated measures of cognitive and social impulsivity were also gathered. Results indicate that attentional control has both cognitive and social/emotional implications. Performance on negative priming and facilitation trials from the Flanker task predicted grades in core courses, social functioning measures, and cognitive and social impulsivity ratings. However, beneficial effects for academic and social functioning associated with inhibition were less prevalent in those demonstrating a greater ability to respond to facilitory cues. There was also some evidence that high levels of facilitation were less beneficial to academic performance, and female students were more likely to exceed optimal levels of facilitory processing. Furthermore, lower negative priming was ''S'K 'i\':y-: -'*' - r " j«v ; ''*.' iij^y Inhibition, Facilitation and Social Competence 3 associated with classroom-rated distraction and hyperactivity, but the relationship between inhibition and social aspects of impulsivity was stronger for adolescents with learning or reading problems, and the relationship between inhibition and cognitive impulsivity was stronger for male students. In most cases, attentional measures were predictive of performance outcomes independent of traditional psychometric measures of cognitive functioning. >,, These findings provide support for neuropsychological models linking inhibition to control of interference and arousal, and emphasize the fundamental role of attention in everyday adolescent activities. The findings also warrant further investigation into the ways which inhibitory and facilitory attentional processes interact, and the contextdependent nature of attentional control.associated with classroom-rated distraction and hyperactivity, but the relationship between inhibition and social aspects of impulsivity was stronger for adolescents with learning or reading problems, and the relationship between inhibition and cognitive impulsivity was stronger for male students. In most cases, attentional measures were predictive of performance outcomes independent of traditional psychometric measures of cognitive functioning. >,, These findings provide support for neuropsychological models linking inhibition to control of interference and arousal, and emphasize the fundamental role of attention in everyday adolescent activities. The findings also warrant further investigation into the ways which inhibitory and facilitory attentional processes interact, and the contextdependent nature of attentional control.

Force potentiation as a modulator of contractile performance: Implications for control of skeletal muscle force and energetics of work

This thesis investigated the modulation of dynamic contractile function and energetics of work by posttetanic potentiation (PTP). Mechanical experiments were conducted in vitro using software-controlled protocols to stimulate/determine contractile function during ramp shortening, and muscles were frozen during parallel incubations for biochemical analysis. The central feature of this research was the comparison of fast hindlimb muscles from wildtype and skeletal myosin light chain kinase knockout (skMLCK-/-) mice that does not express the primary mechanism for PTP: myosin regulatory light chain (RLC) phosphorylation. In contrast to smooth/cardiac muscles where RLC phosphorylation is indispensable, its precise physiological role in skeletal muscle is unclear. It was initially determined that tetanic potentiation was shortening speed dependent, and this sensitivity of the PTP mechanism to muscle shortening extended the stimulation frequency domain over which PTP was manifest. Thus, the physiological utility of RLC phosphorylation to augment contractile function in vivo may be more extensive than previously considered. Subsequent experiments studied the contraction-type dependence for PTP and demonstrated that the enhancement of contractile function was dependent on force level. Surprisingly, in the absence of RLC phosphorylation, skMLCK-/- muscles exhibited significant concentric PTP; consequently, up to ~50% of the dynamic PTP response in wildtype muscle may be attributed to an alternate mechanism. When the interaction of PTP and the catchlike property (CLP) was examined, we determined that unlike the acute augmentation of peak force by the CLP, RLC phosphorylation produced a longer-lasting enhancement of force and work in the potentiated state. Nevertheless, despite the apparent interference between these mechanisms, both offer physiological utility and may be complementary in achieving optimal contractile function in vivo. Finally, when the energetic implications of PTP were explored, we determined that during a brief period of repetitive concentric activation, total work performed was ~60% greater in wildtype vs. skMLCK-/- muscles but there was no genotype difference in High-Energy Phosphate Consumption or Economy (i.e. HEPC: work). In summary, this thesis provides novel insight into the modulatory effects of PTP and RLC phosphorylation, and through the observation of alternative mechanisms for PTP we further develop our understanding of the history-dependence of fast skeletal muscle function.

New statistical methods to assess the effect of time-dependent exposures in case-control studies

Contexte. Les études cas-témoins sont très fréquemment utilisées par les épidémiologistes pour évaluer l’impact de certaines expositions sur une maladie particulière. Ces expositions peuvent être représentées par plusieurs variables dépendant du temps, et de nouvelles méthodes sont nécessaires pour estimer de manière précise leurs effets. En effet, la régression logistique qui est la méthode conventionnelle pour analyser les données cas-témoins ne tient pas directement compte des changements de valeurs des covariables au cours du temps. Par opposition, les méthodes d’analyse des données de survie telles que le modèle de Cox à risques instantanés proportionnels peuvent directement incorporer des covariables dépendant du temps représentant les histoires individuelles d’exposition. Cependant, cela nécessite de manipuler les ensembles de sujets à risque avec précaution à cause du sur-échantillonnage des cas, en comparaison avec les témoins, dans les études cas-témoins. Comme montré dans une étude de simulation précédente, la définition optimale des ensembles de sujets à risque pour l’analyse des données cas-témoins reste encore à être élucidée, et à être étudiée dans le cas des variables dépendant du temps. Objectif: L’objectif général est de proposer et d’étudier de nouvelles versions du modèle de Cox pour estimer l’impact d’expositions variant dans le temps dans les études cas-témoins, et de les appliquer à des données réelles cas-témoins sur le cancer du poumon et le tabac. Méthodes. J’ai identifié de nouvelles définitions d’ensemble de sujets à risque, potentiellement optimales (le Weighted Cox model and le Simple weighted Cox model), dans lesquelles différentes pondérations ont été affectées aux cas et aux témoins, afin de refléter les proportions de cas et de non cas dans la population source. Les propriétés des estimateurs des effets d’exposition ont été étudiées par simulation. Différents aspects d’exposition ont été générés (intensité, durée, valeur cumulée d’exposition). Les données cas-témoins générées ont été ensuite analysées avec différentes versions du modèle de Cox, incluant les définitions anciennes et nouvelles des ensembles de sujets à risque, ainsi qu’avec la régression logistique conventionnelle, à des fins de comparaison. Les différents modèles de régression ont ensuite été appliqués sur des données réelles cas-témoins sur le cancer du poumon. Les estimations des effets de différentes variables de tabac, obtenues avec les différentes méthodes, ont été comparées entre elles, et comparées aux résultats des simulations. Résultats. Les résultats des simulations montrent que les estimations des nouveaux modèles de Cox pondérés proposés, surtout celles du Weighted Cox model, sont bien moins biaisées que les estimations des modèles de Cox existants qui incluent ou excluent simplement les futurs cas de chaque ensemble de sujets à risque. De plus, les estimations du Weighted Cox model étaient légèrement, mais systématiquement, moins biaisées que celles de la régression logistique. L’application aux données réelles montre de plus grandes différences entre les estimations de la régression logistique et des modèles de Cox pondérés, pour quelques variables de tabac dépendant du temps. Conclusions. Les résultats suggèrent que le nouveau modèle de Cox pondéré propose pourrait être une alternative intéressante au modèle de régression logistique, pour estimer les effets d’expositions dépendant du temps dans les études cas-témoins