Hydraulisen kuristinmallin ja liikealustan ohjauksen kehittäminen reaaliaikasimulointiin

Diplomityön ensimmäisessä vaiheessa tutkittiin hydraulisen kuristimen ominaisuuksia ja esiteltiin numeerisesti tehokas kuristinmalli käyttäenpolynomifunktiota virtauksen laminaarisen ja transitioalueen kuvaukseen. Puoliempiirisen mallin paremmuus tulee esille siinä, että kuristimen geometriatietoja ei tarvita laskettaessa virtausta paine-eron perusteella. Reaaliaikasimuloinnissa esiintyy kompromisseja tarkkuuden ja laskentanopeuden välillä. Tätä asiaa tutkittiin kahden virtausalueen kuristinmallilla. Transition paine-eron ja integrointiaika-askelen valinnan vaikutus tarkkuuteen ja laskentanopeuteen tutkittiin. Toisessa vaiheessa tutkittiin mahdollisimman hyvän liiketuntuman tuottamista liikealustalla ohjaussignaalia kehittämällä. Liikealustan liikeradan rajallisuudesta johtuen ohjauksessa on perinteisesti käytetty washout-suodatusta, joka erottelee simuloitavan järjestelmän kiihtyvyyssignaalista vain nopeatkiihtyvyydet. Tässä työssä tutkittiin hitaiden kiihtyvyyksien ottamista mukaan liikealustan ohjaukseen liikealustan liikeradan puitteissa. Tämä toteutettiin kuvaamalla hitaat kiihtyvyydet kallistamalla liikealustaa, jolloin käyttäjään kohdistuva voima saatiin kuvattua gravitaatiota hyväksi käyttäen.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

Regulation of B Cell Gene Expression and Function by Ikaros, Helios and Bcl6

B lymphocytes constitute a key branch of adaptive immunity by providing specificity to recognize a vast variety of antigens by B cell antigen receptors (BCR) and secreted antibodies. Antigen recognition activates the cells and can produce antibody secreting plasma cells via germinal center reaction that leads to the maturation of antigen recognition affinity and switching of antibody effector class. The specificity of antigen recognition is achieved through a multistep developmental pathway that is organized by interplay of transcription factors and signals through BCR. Lymphoid malignancies arise from different stages of development in abnormal function of transcriptional regulation. To understand the B cell development and the function of B cells, a thorough understanding of the regulation of gene expression is important. The transcription factors of the Ikaros family and Bcl6 are frequently associated with lymphoma generation. The aim of this study was to reveal the targets of Ikaros, Helios and Bcl6 mediated gene regulation and to find out the function of Ikaros and Helios in B cells. This study uses gene targeted DT40 B cell lines and establishes a role for Ikaros family factors Ikaros and Helios in the regulation of BCR signaling that is important at developmental checkpoints, for cell survival and in activation. Ikaros and Helios had opposing roles in the regulation of BCR signals. Ikaros was found to directly repress the SHIP gene that encodes a signaling lipid-metabolizing enzyme, whereas Helios had activating effect on SHIP expression. The findings demonstrate a balancing function for these two Ikaros family transcription factors in the regulation of BCR signaling as well as in the regulation of gene expression. Bcl6 was found to repress plasma cell gene expression program while maintaining gene expression profile of B cells. Analysis of direct Bcl6 target genes suggested novel mechanisms for Bcl6-mediated suppression of plasma cell differentiation and promoting germinal center phenotype.

Regulation of Spermatogenesis: Differentiation of GFP-labeled Stem Cells and the Function of Cytoplasmic Bridges

During spermatogenesis, different genes are expressed in a strictly coordinated fashion providing an excellent model to study cell differentiation. Recent identification of testis specific genes and the development of green fluorescence protein (GFP) transgene technology and an in vivo system for studying the differentiation of transplanted male germ cells in infertile testis has opened new possibilities for studying the male germ cell differentiation at molecular level. We have employed these techniques in combination with transillumination based stage recognition (Parvinen and Vanha-Perttula, 1972) and squash preparation techniques (Parvinen and Hecht, 1981) to study the regulation of male germ cell differentiation. By using transgenic mice expressing enhanced-(E)GFP as a marker we have studied the expression and hormonal regulation of beta-actin and acrosin proteins in the developmentally different living male germ cells. Beta-actin was demonstrated in all male germ cells, whereas acrosin was expressed only in late meiotic and in postmeiotic cells. Follicle stimulating hormone stimulated b-actin-EGFP expression at stages I-VI and enhanced the formation of microtubules in spermatids and this way reduced the size of the acrosomic system. When EGFP expressing spermatogonial stem cells were transplanted into infertile mouse testis differentiation and the synchronized development of male germ cells could be observed during six months observation time. Each colony developed independently and maintained typical stage-dependent cell associations. Furthermore, if more than two colonies were fused, each of them was adjusted to one stage and synchronized. By studying living spermatids we were able to demonstrate novel functions for Golgi complex and chromatoid body in material sharing between neighbor spermatids. Immunosytochemical analyses revealed a transport of haploid cell specific proteins in spermatids (TRA54 and Shippo1) and through the intercellular bridges (TRA54). Cytoskeleton inhibitor (nocodazole) demonstrated the importance of microtubules in material sharing between spermatids and in preserving the integrity of the chromatoid body. Golgi complex inhibitor, brefeldin A, revealed the great importance of Golgi complex i) in acrosomic system formation ii) TRA54 translation and in iii) granule trafficking between spermatids.

Thyroid function in the elderly and sex hormones in elderly men: reference intervals and associations with health

Aims: The aims were to create clinically feasible reference intervals for thyroidstimulating hormone (TSH) and free thyroxine (FT4) and to analyze associations between thyroid function and self-rated health, neuropsychiatric symptoms, depression and dementia in the elderly. The second aim was also to establish reference intervals for sex hormones and to analyze associations between sex hormone levels and self-rated health, symptoms, depression and dementia in elderly men. Subjects and methods: The study population comprised 1252 subjects aged 65 years or over, living in the municipality of Lieto, south-western Finland. Self-rated health, life satisfaction, symptoms, depression, and dementia were assessed with specific questions, clinical examination and tools such as the Zung Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH, FT4 or sex hormone levels were assessed. Levels of TSH and FT4 in thyroid disease–free women and women treated with thyroxine were also compared. Results: Elevated concentrations of thyroid peroxidase antibodies (TPOAb) or thyroglobulin antibodies (TgAb) were found to have a marked effect on the upper reference limit for TSH among women, who were thyroid antibody positive more higher than suggested in several recent guidelines. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most neuropsychiatric symptoms in the thyroid disease-free population. Although women with thyroxine treatment for primary hypothyroidism had far higher TSH levels than thyroid disease-free women, there were no differences between thyroid-disease free women and women with stable thyroxine treatment regarding self-rated health, life satisfaction or symptoms. Age had a significant positive association with luteinizing hormone (LH), follicle 2 practice, one range in men aged 65 years or over can be used for T, E2 and FSH measured with the AutoDelfia method, but two separate reference intervals should be used for fT, LH and SHBG. After adjustment for age, higher levels of T and fT were associated with better self-rated health (SRH) in the reference population. After adjustment for age and body mass index (BMI), there were no associations between sex hormone concentrations and self-rated health, life satisfaction or most symptoms in concentration. Conclusion: Age-specific reference intervals were derived for thyroid function and sex hormones based on comprehensive data from a community-dwelling population with a high participation rate. The results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. Older age or being overweight symptoms among elderly men. The associations of single symptoms with T levels were inconsistent among elderly men, although the association of low T level with diagnosed depression might be clinically significant.

Neck Muscle Function and Adolescent Headache

Muscular function of the neck region may be of importance for the etiology of headache, especially of tension-type headache. However, very few data exist on the association of neck muscle function with different types of headache in adolescents. The main aim of the study was to examine the association of neck muscle function with adolescent headache. The associations between leisure time activities, endurance strength of the upper extremities (UE endurance) and mobility of the neck-shoulder region and adolescent headache were studied. In addition, the associations of force production, EMG/force ratio, co-activation and fatigue characteristics, and cross-sectional area (CSA) of neck muscles with adolescent headache were studied. The study is part of a population-based cohort study of 12-year-old children with and without headache. The study had five phases (years 1998-2003). At the age of 13 years, a sample of 183 adolescents (183/311) participated in endurance strength and mobility measurements of the neck-shoulder region. In addition, the type and level of physical and other leisure activity were elicited with open and structured questions. At the age of 17 years, a random sample of 89 adolescents (89/202) participated in force and EMG measurements of the neck-shoulder muscles. In addition, at the age of 17 years, a sample of 65 adolescents (65/89) participated in CSA measurements of the neck muscles. At the age of 13 years, intensive participation in overall sports activity was associated with migraine. Frequent computer use was associated both with migraine and tension-type headache. The type of sports or other leisure activity classified them on the basis of body loading was not associated with headache type. In girls, low UE endurance of both sides, and low cervical rotation of the dominant side, were associated with tension-type headache, and low UE endurance of non-dominant side with migraine. In boys, no associations occurred between UE endurance and mobility variables and headache types. At the age of 17 years, in girls, high EMG/force ratios between the EMG of the left agonist sternocleidomastoid muscle (SCM) and maximal neck flexion and neck rotation force to the right side as well as high co-activation of right antagonist cervical erector spinae (CES) muscles during maximal neck flexion force were associated with migraine-type headache. In girls, neck force production was not associated with headache types but low left shoulder flexion force was associated with tension-type headache. In boys, no associations were found between EMG and force variables and headache. Increased SCM muscles fatigue of both sides was associated with tension-type headache. In boys, the small CSA of the right SCM muscle and, in girls, of combined right SCM and scalenus muscles was associated with tension-type headache. Similarly, in boys, the large CSA of the right SCM muscle, of the combined right SCM and scalenus muscles, of the left semispinalis capitis muscle, of the combined left semispinalis and splenius muscles was associated with migraine. No other differences in the CSA of neck flexion or extension muscles were found. Differences in the neuromucular function of the neck-shoulder muscles were associated with adolescent headache, especially in girls. Differences in the cross-sectional area of unilateral neck muscles were associated with headache, especially in boys. Differences in the neuromuscular function and in the cross-sectional area of the neck muscles also occurred between different types of headache. It remains to be established whether the findings are primary or secondary to adolescent migraine and tension headache. Keywords: adolescent, cross-sectional area, electromyography, endurance strength, fatigue, force, headache, leisure time activity, migraine, mobility, neck muscles, tension-type headache

Threat Simulation- The Function of Dreaming?

Dreaming is a pure form of phenomenality, created by the brain untouched by external stimulation or behavioral activity, yet including a full range of phenomenal contents. Thus, it has been suggested that the dreaming brain could be used as a model system in a biological research program on consciousness (Revonsuo, 2006). In the present thesis, the philosophical view of biological realism is accepted, and thus, dreaming is considered as a natural biological phenomenon, explainable in naturalistic terms. The major theoretical contribution of the present thesis is that it explores dreaming from a multidisciplinary perspective, integrating information from various fields of science, such as dream research, consciousness research, evolutionary psychology, and cognitive neuroscience. Further, it places dreaming into a multilevel framework, and investigates the constitutive, etiological, and contextual explanations for dreaming. Currently, the only theory offering a full multilevel explanation for dreaming, that is, a theory including constitutive, etiological, and contextual level explanations, is the Threat Simulation Theory (TST) (Revonsuo, 2000a; 2000b). The empirical significance of the present thesis lies in the tests conducted to test this specific theory put forth to explain the form, content, and biological function of dreaming. The first step in the empirical testing of the TST was to define exact criteria for what is a ‘threatening event’ in dreams, and then to develop a detailed and reliable content analysis scale with which it is possible to empirically explore and quantify threatening events in dreams. The second step was to seek answers to the following questions derived from the TST: How frequent threatening events are in dreams? What kind of qualities these events have? How threatening events in dreams relate to the most recently encoded or the most salient memory traces of threatening events experienced in waking life? What are the effects of exposure to severe waking life threat on dreams? The results reveal that threatening events are relatively frequent in dreams, and that the simulated threats are realistic. The most common threats include aggression, are targeted mainly against the dream self, and include simulations of relevant and appropriate defensive actions. Further, real threat experiences activate the threat simulation system in a unique manner, and dream content is modulated by the activation of long term episodic memory traces with highest negative saliency. To sum up, most of the predictions of the TST tested in this thesis received considerable support. The TST presents a strong argument that explains the specific design of dreams as threat simulations. The TST also offers a plausible explanation for why dreaming would have been selected for: because dreaming interacted with the environment in such a way that enhanced fitness of ancestral humans. By referring to a single threat simulation mechanism it furthermore manages to explain a wide variety of dream content data that already exists in the literature, and to predict the overall statistical patterns of threat content in different samples of dreams. The TST and the empirical tests conducted to test the theory are a prime example of what a multidisciplinary approach to mental phenomena can accomplish. Thus far, dreaming seems to have always resided in the periphery of science, never regarded worth to be studied by the mainstream. Nevertheless, when brought to the spotlight, the study of dreaming can greatly benefit from ideas in diverse branches of science. Vice versa, knowledge learned from the study of dreaming can be applied in various disciplines. The main contribution of the present thesis lies in putting dreaming back where it belongs, that is, into the spotlight in the cross-road of various disciplines.

Vascular Function in Chronic Kidney Disease and in Renovascular Disease

Cardiovascular mortality is 15 to 30 times higher in patients with chronic kidney disease than in the age-adjusted general population. Even minor renal dysfunction predicts cardiovascular events and death in the general population. In patients with atherosclerotic renovascular disease the annual cardiovascular event and death rate is even higher. The abnormalities in coronary and peripheral artery function in the different stages of chronic kidney disease and in renovascular disease are still poorly understood, nor have the cardiac effects of renal artery revascularization been well characterized, although considered to be beneficial. This study was conducted to characterize myocardial perfusion and peripheral endothelial function in patients with chronic kidney disease and in patients with atherosclerotic renovascular disease. Myocardial perfusion was measured with positron emission tomography (PET) and peripheral endothelial function with brachial artery flow-mediated dilatation. It has been suggested that the poor renal outcomes after the renal artery revascularization could be due to damage in the stenotic kidney parenchyma; especially the reduction in the microvascular density, changes mainly evident at the cortical level which controls almost 80% of the total renal blood flow. This study was also performed to measure the effect of renal artery stenosis revascularization on renal perfusion in patients with renovascular disease. In order to do that a PET-based method for quantification of renal perfusion was developed. The coronary flow reserve of patients with chronic kidney disease was similar to the coronary flow reserve of healthy controls. In renovascular disease the coronary flow reserve was, however, markedly reduced. Flow-mediated dilatation of brachial artery was decreased in patients with chronic kidney disease compared to healthy controls, and even more so in patients with renovascular disease. After renal artery stenosis revascularization, coronary vascular function and renal perfusion did not improve in patients with atherosclerotic renovascular disease, but in patients with bilateral renal artery stenosis, flow-mediated dilatation improved. Chronic kidney disease does not significantly affect coronary vascular function. On the contrary, coronary vascular function was severely deteriorated in patients with atherosclerotic renovascular disease, possibly because of diffuse coronary artery disease and/or diffuse microvascular disease. The peripheral endothelial function was disturbed in patients with chronic kidney disease and even more so in patient with atherosclerotic renovascular disease. Renal artery stenosis dilatation does not seem to offer any benefits over medical treatment in patients with renovascular disease, since revascularization does not improve coronary vascular function or renal perfusion.