Berry polyphenol absorption and the effect of northern berries on metabolism, ectopic fat accumulation, and associated diseases

The prevalence of obesity and type 2 diabetes has increased at an alarming rate in developed countries. It seems in the light of current knowledge that metabolic syndrome may not develop at all without NAFLD, and NAFLD is estimated to be as common as metabolic syndrome in western population (23 % occurrence). Fat in the liver is called ectopic fat, which is triacylglycerols within the cells of non-adipose tissue. Serum alanine aminotransferase (ALT) values correlate positively with liver fat proportions, and increased activity of ALT predicts type 2 diabetes independently from obesity. Berries, high in natural bioactive compounds, have indicated the potential to reduce the risk of obesity-related diseases. Ectopic fat induces common endocrine excretion of adipose tissue resulting in the overproduction of inflammatory markers, which further induce insulin resistance by multiple mechanisms. Insulin resistance inducing hyperinsulinemia and lipolysis in adipocytes increases the concentration of free fatty acids and consequently causes further fat accumulation in hepatocytes. Polyphenolic fractions of berries have been shown to reverse inflammatory reaction cascades in in vitro and animal studies, and moreover to decrease ectopic fat accumulation. The aim of this thesis was to explore the role of northern berries in obesity-related diseases. The absorption and metabolism of selected berry polyphenols, flavonol glycosides and anthocyanins, was investigated in humans, and metabolites of the studied compounds were identified in plasma and urine samples (I, II). Further, the effects of berries on the risk factors of metabolic syndrome were studied in clinical intervention trials (III, IV), and the different fractions of sea buckthorn berry were tested for their ability to reduce postprandial glycemia and insulinemia after high-glucose meal in a postprandial study with humans (V). The marked impact of mixed berries on plasma ALT values (III), as well as indications of the positive effects of sea buckthorn, its fractions and bilberry on omental adiposity and adhesion molecules (IV) were observed. In study V, sea buckthorn and its polyphenol fractions had a promising effect on potprandial metabolism after high-glucose meal. In the literature review, the possible mechanisms behind the observed effects have been discussed with a special emphasis on ectopic fat accumulation. The literature review indicated that especially tannins and flavonoids have shown potential in suppressing diverse reaction cascades related to systemic inflammation, ectopic fat accumulation and insulin resistance development.

Loss Modelling of Three-Level Inverters controlled with Space Vector Modulation Technique

The objective of this master’s thesis is to investigate the loss behavior of three-level ANPC inverter and compare it with conventional NPC inverter. The both inverters are controlled with mature space vector modulation strategy. In order to provide the comparison both accurate and detailed enough NPC and ANPC simulation models should be obtained. The similar control model of SVM is utilized for both NPC and ANPC inverter models. The principles of control algorithms, the structure and description of models are clarified. The power loss calculation model is based on practical calculation approaches with certain assumptions. The comparison between NPC and ANPC topologies is presented based on results obtained for each semiconductor device, their switching and conduction losses and efficiency of the inverters. Alternative switching states of ANPC topology allow distributing losses among the switches more evenly, than in NPC inverter. Obviously, the losses of a switching device depend on its position in the topology. Losses distribution among the components in ANPC topology allows reducing the stress on certain switches, thus losses are equally distributed among the semiconductors, however the efficiency of the inverters is the same. As a new contribution to earlier studies, the obtained models of SVM control, NPC and ANPC inverters have been built. Thus, this thesis can be used in further more complicated modelling of full-power converters for modern multi-megawatt wind energy conversion systems.

People and the intertidal : human induced changes, biodiversity loss, livelihood implications and management in the Western Indian Ocean

Vad händer i tidvattenzonen? Var går gränsen mellan land och hav, vad händer i tidvattenzonen och vem ansvarar för detta? I västra Indiska oceanen (VIO) kan avståndet mellan den lägsta nivån för lågvattnet och den högsta nivån för högvattnet vara flera kilometer och nivåskillnaderna upp till 6 meter och detta skapar ett stort och föränderligt område. Syftet med min avhandling är att öka förståelsen för tidvattenzonen i tropiska och subtropiska västra Indiska oceanen. Sammanfattningsvis visar mina studier att det finns ett mycket stort värde i den komplexa tidvattenzonen, men också att det här området hotas från både land och hav, genom t.ex. överexploatering, erosion och föroreningar. Uttnyttjandet av tidvattenzonen är stort och min avhandling har visat att aktiviteter såsom fiske i form av plocking av musslor och andra ryggradslösa djur och hamnaktiviteter påverkar den biologiska mångfalden negativt, vilket leder till försämrad levnadsstandard för resursutnyttjande människor i regionen. För att förbättra situationen krävs det mer forskning, miljöövervakning och bättre förvaltning av tidvattenzonen. Experter i regionen har rangordnat förslag på förvaltningsstrategier som skulle kunna testas för att förbättra miljön och skapa ett mer hållbart nyttjande. Avhandlingen visar även att det är möjligt att använda fjärranalysteknik såsom satellitbildsanalys för att kvantifiera mängden sjögräsvegetation (i form av biomassa), vilket kan ha stor betydelse för att förbättra storskalig miljöövervakning av kustnära naturtyper (habitat). I avhandlingsarbetet har jag använt mig av ett multidisciplinärt tillvägagångssätt och använt metoder såsom ekologisk och biologisk provtagning, intervjuer, observationer, diskussionsgrupper, frågeformulär och fjärranalys. Resultaten presenterade i denna avhandling ger en ökad kunskap om tidvattenzonen i utvecklingsländerna inom VIO-regionen som kan användas för att initiera och fortsätta att utveckla hållbara förvaltningsstrategier av biologiska resurser.

FAT-luokkien määritys hitsatuille levyliitoksille käyttämällä lineaarisen murtumismekaniikan särönkasvun simulointia

Työssä tutkittiin hitsattujen levyliitosten väsymiskestävyyden mitoitusarvoja. Hitsien väsymiskestävyyden mitoitusarvot määritettiin lineaarista murtumismekaniikkaa soveltavalla 2D FEM-laskentaohjelmalla. Murtumismekaanisen laskennan tuloksista määriteltiin, eri liitosgeometrioiden ja kuormitustyyppien mukaisia, nimellisen jännityksen väsymismitoitusmenetelmää vastaavia FAT-luokkia, joissa on huomioitu rakenteellinen jännitys hitsiä vastaan kohtisuorassa suunnassa. Tutkittujen liitosten geometriat olivat pääsääntöisesti poikkeavia mitoitusstandardien ja ohjeiden sisältämistä taulukkotapauksista. Laskennassa otettiin huomioon hitsien liittymiskulma perusaineeseen, rajaviivan pyöristykset ja vajaa hitsautumissyvyys. Kuormitustyyppien vaihtelua tutkittiin rakenteellisen jännityksen taivutusosuuden muutoksilla ja kuormaa kantavien X-liitosten risteävien kuormituksien suhteellisilla suuruuksilla. Väsymiskestävyydet määritettiin kuormituskohtaisille kalvo- ja taivutusjännityksille sekä näiden jännitysjakaumien keskiarvoille. Työssä saatuja FAT-luokkia voidaan hyödyntää vastaavien geometrioiden ja kuormitusten yhteydessä, sekä interpoloimalla myös tuloksien väliarvoissa. Työssä käytetyillä menetelmillä voidaan parantaa nimellisen jännityksen mitoitusmenetelmän tarkkuutta ja laajentaa sitä koskemaan myös taulukkotapausten ulkopuolisia liitoksia. Työn tuloksissa on esitetty FAT-luokkia T-, X- ja päittäisliitoksille ja näiden eri kuormitusyhdistelmille.

The Effects of Anesthetic Induced Loss of Consciousness on Quantitative Electroen Cephalogram, and Bispectral and Spectral Entropy Indices. Studies on Healthy Male

Changes in the electroencephalography (EEG) signal have been used to study the effects of anesthetic agents on the brain function. Several commercial EEG based anesthesia depth monitors have been developed to measure the level of the hypnotic component of anesthesia. Specific anesthetic related changes can be seen in the EEG, but still it remains difficult to determine whether the subject is consciousness or not during anesthesia. EEG reactivity to external stimuli may be seen in unconsciousness subjects, in anesthesia or even in coma. Changes in regional cerebral blood flow, which can be measured with positron emission tomography (PET), can be used as a surrogate for changes in neuronal activity. The aim of this study was to investigate the effects of dexmedetomidine, propofol, sevoflurane and xenon on the EEG and the behavior of two commercial anesthesia depth monitors, Bispectral Index (BIS) and Entropy. Slowly escalating drug concentrations were used with dexmedetomidine, propofol and sevoflurane. EEG reactivity at clinically determined similar level of consciousness was studied and the performance of BIS and Entropy in differentiating consciousness form unconsciousness was evaluated. Changes in brain activity during emergence from dexmedetomidine and propofol induced unconsciousness were studied using PET imaging. Additionally, the effects of normobaric hyperoxia, induced during denitrogenation prior to xenon anesthesia induction, on the EEG were studied. Dexmedetomidine and propofol caused increases in the low frequency, high amplitude (delta 0.5-4 Hz and theta 4.1-8 Hz) EEG activity during stepwise increased drug concentrations from the awake state to unconsciousness. With sevoflurane, an increase in delta activity was also seen, and an increase in alpha- slow beta (8.1-15 Hz) band power was seen in both propofol and sevoflurane. EEG reactivity to a verbal command in the unconsciousness state was best retained with propofol, and almost disappeared with sevoflurane. The ability of BIS and Entropy to differentiate consciousness from unconsciousness was poor. At the emergence from dexmedetomidine and propofol induced unconsciousness, activation was detected in deep brain structures, but not within the cortex. In xenon anesthesia, EEG band powers increased in delta, theta and alpha (8-12Hz) frequencies. In steady state xenon anesthesia, BIS and Entropy indices were low and these monitors seemed to work well in xenon anesthesia. Normobaric hyperoxia alone did not cause changes in the EEG. All of these results are based on studies in healthy volunteers and their application to clinical practice should be considered carefully.

Identification of Some Additional Loss Components in High-Power Low-Voltage Permanent Magnet Generators

Permanent magnet generators (PMG) represent the cutting edge technology in modern wind mills. The efficiency remains high (over 90%) at partial loads. To improve the machine efficiency even further, every aspect of machine losses has to be analyzed. Additional losses are often given as a certain percentage without providing any detailed information about the actual calculation process; meanwhile, there are many design-dependent losses that have an effect on the total amount of additional losses and that have to be taken into consideration. Additional losses are most often eddy current losses in different parts of the machine. These losses are usually difficult to calculate in the design process. In this doctoral thesis, some additional losses are identified and modeled. Further, suggestions on how to minimize the losses are given. Iron losses can differ significantly between the measured no-load values and the loss values under load. In addition, with embedded magnet rotors, the quadrature-axis armature reaction adds losses to the stator iron by manipulating the harmonic content of the flux. It was, therefore, re-evaluated that in salient pole machines, to minimize the losses and the loss difference between the no-load and load operation, the flux density has to be kept below 1.5 T in the stator yoke, which is the traditional guideline for machine designers. Eddy current losses may occur in the end-winding area and in the support structure of the machine, that is, in the finger plate and the clamping ring. With construction steel, these losses account for 0.08% of the input power of the machine. These losses can be reduced almost to zero by using nonmagnetic stainless steel. In addition, the machine housing may be subjected to eddy current losses if the flux density exceeds 1.5 T in the stator yoke. Winding losses can rise rapidly when high frequencies and 10–15 mm high conductors are used. In general, minimizing the winding losses is simple. For example, it can be done by dividing the conductor into transposed subconductors. However, this comes with the expense of an increase in the DC resistance. In the doctoral thesis, a new method is presented to minimize the winding losses by applying a litz wire with noninsulated strands. The construction is the same as in a normal litz wire but the insulation between the subconductors has been left out. The idea is that the connection is kept weak to prevent harmful eddy currents from flowing. Moreover, the analytical solution for calculating the AC resistance factor of the litz-wire is supplemented by including an end-winding resistance in the analytical solution. A simple measurement device is developed to measure the AC resistance in the windings. In the case of a litz-wire with originally noninsulated strands, vacuum pressure impregnation (VPI) is used to insulate the subconductors. In one of the two cases studied, the VPI affected the AC resistance factor, but in the other case, it did not have any effect. However, more research is needed to determine the effect of the VPI on litz-wire with noninsulated strands. An empirical model is developed to calculate the AC resistance factor of a single-layer formwound winding. The model includes the end-winding length and the number of strands and turns. The end winding includes the circulating current (eddy currents that are traveling through the whole winding between parallel strands) and the main current. The end-winding length also affects the total AC resistance factor.

Alpha- and gamma-melanocyte stimulating hormones in obesity. A study of the key central areas of metabolic regulation

The melanocortin system is an important regulator of feeding, energy metabolism,and cardiovascular function and it consists of the pro-opiomelanocortin (POMC) derived melanocyte stimulating hormones (α-, β- and γ-MSH) and their endogenous melanocortin receptors, MC1R to MC5R. In the hypothalamus, α-MSH reduces food intake, and increases energy expenditure and sympathetic tone by binding to MC4R. Mutations affecting the MC4R gene lead to obesity in mammals. On the other hand, the metabolic effects of MC3R stimulation using agonists such as the endogenously expressed γ-MSH have been less extensively explored. The main objective of this study was to investigate the long-term effects of increased melanocortin tone in key areas of metabolic regulation in the central nervous system (CNS) in order to investigate the sitespecific roles of both α-MSH and γ-MSH. The aim was to stereotaxically induce local overexpression of single melanocortin peptides using lentiviral vectors expressing α-MSH (LVi-α-MSH-EGFP) and γ-MSH (LVi-γ-MSH-EGFP). The lentiviral vectors were shown to produce a long-term overexpression and biologically active peptides in cell-based assays. The LVi-α-MSHEGFP was targeted to the arcuate nucleus in the hypothalamus of diet induced obese mice where it reduced weight gain and adiposity independently of food intake. When the nucleus tractus solitarus in the brainstem was targeted, the LVi-α-MSH-EGFP treatment was shown to cause a small decrease in adiposity, which did not impact weight development. However, the α-MSH treatment increased heart rate, which was attenuated by adrenergic receptor blockade indicative of increased sympathetic activity. The LVi-γ-MSH-EGFP was targeted to the hypothalamus where it decreased fat mass in mice eating the standard diet, but the effect was abated if animals consumed a high-fat Western type diet. When the diet induced obese mice were subjected again to the standard diet, the LVi-γ-MSH-EGFP treated animals displayed increased weight loss and reduced adiposity. These results indicate that the long-term central anti-obesity effects of α-MSH are independent of food intake. In addition, overexpression of α-MSH in the brain stem efficiently blocked the development of adiposity, but increased sympathetic tone. The evidence presented in this thesis also indicates that selective MC3R agonists such as γ-MSH could be potential therapeutics in combination with low fat diets.

Phenomena and mechanisms in purification of animal fat

Työn tarkoitus oli tutkia eläinrasvan puhdistusta biodieselin valmistusta varten. Eläinrasvaa syntyy elintarviketeollisuuden sivutuotteena ja sitä saadaan myös myymättä jääneistä elintarvikkeista. Rasva sisältää epäpuhtauksia, jotka on poistettava ennen biodieselprosessia. Tässä työssä tutkittavat epäpuhtaudet ovat typpi, fosfori, rauta, natrium, kalsium ja magnesium. Puhdistusmenetelminä käytettiin saostamista sitruunahapolla sekä adsorbointia kahdella eri adsorbentilla. Tavoitteena oli selvittää riittävä määrä happoa ja adsorbenttia sekä tutkia puhdistuksen mekanismia. Lisäksi tarkasteltiin lämpötilan vaikutusta adsorption aikana.

Analytic evaluation of three-phase short circuit demagnetization and hysteresis loss risk in rotor-surface-magnet Permanent-Magnet Synchronous Machines

Permanent magnet synchronous machines (PMSM) have become widely used in applications because of high efficiency compared to synchronous machines with exciting winding or to induction motors. This feature of PMSM is achieved through the using the permanent magnets (PM) as the main excitation source. The magnetic properties of the PM have significant influence on all the PMSM characteristics. Recent observations of the PM material properties when used in rotating machines revealed that in all PMSMs the magnets do not necessarily operate in the second quadrant of the demagnetization curve which makes the magnets prone to hysteresis losses. Moreover, still no good analytical approach has not been derived for the magnetic flux density distribution along the PM during the different short circuits faults. The main task of this thesis is to derive simple analytical tool which can predict magnetic flux density distribution along the rotor-surface mounted PM in two cases: during normal operating mode and in the worst moment of time from the PM’s point of view of the three phase symmetrical short circuit. The surface mounted PMSMs were selected because of their prevalence and relatively simple construction. The proposed model is based on the combination of two theories: the theory of the magnetic circuit and space vector theory. The comparison of the results in case of the normal operating mode obtained from finite element software with the results calculated with the proposed model shows good accuracy of model in the parts of the PM which are most of all prone to hysteresis losses. The comparison of the results for three phase symmetrical short circuit revealed significant inaccuracy of the proposed model compared with results from finite element software. The analysis of the inaccuracy reasons was provided. The impact on the model of the Carter factor theory and assumption that air have permeability of the PM were analyzed. The propositions for the further model development are presented.

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonance

Effect of bariatric surgery on adipose tissue distribution in severely obese patients

Background and aim: Bariatric surgery leads to sustain weight loss, improve metabolic and lipids profiles and ultimately leads to remission of type 2 diabetes (T2DM) in some obese individuals. The aim of the project is to evaluate the effect of bariatric on abdominal fat distribution in severely obese T2DM and non-T2DM obese patients. Study design and methods: A total of 23 morbidly obese subjects (mean ± SD body mass index 43.0 ± 3.6 kg/m2, age 46.5 ± 9.0 years) were recruited from the lager multicenter SLEEVEPASS studies (ClinicalTrials.gov/NCT00793143). 10 healthy age-matched non-obese individuals served as controls. The obese patients were studied before and 6 months after surgery. At baseline, there were 9 T2DMs and 14 non-diabetics. After surgery, there were 5 remitters and 4 nonremitters. Whole body magnetic resonance imaging including the abdominal regions was performed for the obese subjects before and 6 months after surgery and for the controls once. Abdominal fat were compartmentalized and analyzed. Results: At 6 months of follow-up, BMI in the obese decreased significantly (from 43 ± 4 to 33 ± 2 kg/m2, p < 0.001) with substantial improvement in whole body insulin sensitivity (from 12.2 ± 5.7 to 23.3 ± 8.1 µmol/kg/min, p < 0.001). Intraperitoneal fat mass decreased by 46% (from 3.4 ± 1.1 to 1.9± 1.0 kg, p < 0.001) more than the rest of the compartments. Abdominal visceral compartments in obese correlated with glycemic status independent of surgery. Pre-surgery posterior deep and intraperitoneal fat mass were better predictors of post-surgery glycemic status in obese. Remitters showed significant improvement in whole body insulin sensitivity (from 9.1 ± 2.1 to 20.9 ± 8.4 µmol/kg/min, p = 0.02), fasting glucose decreased significant only in nonremitters (from 7.1 ± 1.1 to 6.0 ± 0.8 mmol/l, p = 0.05) after surgery. There were no differences in extraperitoneal fat mass in remitters and superficial subcutaneous fat in non-remitters but all other compartments decreased significantly 6 months after the surgery Conclusion: Both deep subcutaneous and visceral fat are important contributors to glycemic status in obese subjects. Whereas visceral fat compartments are directly involved in T2DM, superficial subcutaneous may have offered protection against T2DM in obese subjects.