Human genetic variation in the Baltic Sea region: Features of population history and natural selection

In this thesis, the genetic variation of human populations from the Baltic Sea region was studied in order to elucidate population history as well as evolutionary adaptation in this region. The study provided novel understanding of how the complex population level processes of migration, genetic drift, and natural selection have shaped genetic variation in North European populations. Results from genome-wide, mitochondrial DNA and Y-chromosomal analyses suggested that the genetic background of the populations of the Baltic Sea region lies predominantly in Continental Europe, which is consistent with earlier studies and archaeological evidence. The late settlement of Fennoscandia after the Ice Age and the subsequent small population size have led to pronounced genetic drift, especially in Finland and Karelia but also in Sweden, evident especially in genome-wide and Y-chromosomal analyses. Consequently, these populations show striking genetic differentiation, as opposed to much more homogeneous pattern of variation in Central European populations. Additionally, the eastern side of the Baltic Sea was observed to have experienced eastern influence in the genome-wide data as well as in mitochondrial DNA and Y-chromosomal variation – consistent with linguistic connections. However, Slavic influence in the Baltic Sea populations appears minor on genetic level. While the genetic diversity of the Finnish population overall was low, genome-wide and Y-chromosomal results showed pronounced regional differences. The genetic distance between Western and Eastern Finland was larger than for many geographically distant population pairs, and provinces also showed genetic differences. This is probably mainly due to the late settlement of Eastern Finland and local isolation, although differences in ancestral migration waves may contribute to this, too. In contrast, mitochondrial DNA and Y-chromosomal analyses of the contemporary Swedish population revealed a much less pronounced population structure and a fusion of the traces of ancient admixture, genetic drift, and recent immigration. Genome-wide datasets also provide a resource for studying the adaptive evolution of human populations. This study revealed tens of loci with strong signs of recent positive selection in Northern Europe. These results provide interesting targets for future research on evolutionary adaptation, and may be important for understanding the background of disease-causing variants in human populations.

Sampling frequency affects estimates of annual nitrous oxide fluxes

Quantifying nitrous oxide (N(2)O) fluxes, a potent greenhouse gas, from soils is necessary to improve our knowledge of terrestrial N(2)O losses. Developing universal sampling frequencies for calculating annual N(2)O fluxes is difficult, as fluxes are renowned for their high temporal variability. We demonstrate daily sampling was largely required to achieve annual N(2)O fluxes within 10% of the best estimate for 28 annual datasets collected from three continents, Australia, Europe and Asia. Decreasing the regularity of measurements either under- or overestimated annual N(2)O fluxes, with a maximum overestimation of 935%. Measurement frequency was lowered using a sampling strategy based on environmental factors known to affect temporal variability, but still required sampling more than once a week. Consequently, uncertainty in current global terrestrial N(2)O budgets associated with the upscaling of field-based datasets can be decreased significantly using adequate sampling frequencies.

A robust initialization scheme for faster convergence of the dichotomous search algorithm for single frequency estimation

The estimation of the frequency of a sinusoidal signal is a well researched problem. In this work we propose an initialization scheme to the popular dichotomous search of the periodogram peak algorithm(DSPA) that is used to estimate the frequency of a sinusoid in white gaussian noise. Our initialization is computationally low cost and gives the same performance as the DSPA, while reducing the number of iterations needed for the fine search stage. We show that our algorithm remains stable as we reduce the number of iterations in the fine search stage. We also compare the performance of our modification to a previous modification of the DSPA and show that we enhance the performance of the algorithm with our initialization technique.

Effect of metal coating and residual stress on the resonant frequency of MEMS resonators

MEMS resonators are designed for a fixed resonant frequency. Therefore, any shift in the resonant frequency of the final fabricated structure can be a denting factor for its suitability towards a desired application. There are numerous factors which alter the designed resonant frequency of the fabricated resonator such as the metal layer deposited on top of the beam and the residual stresses present in the fabricated structure. While the metal coating, which acts as electrode, increases the stiffness and the effective mass of the composite structure, the residual stress increases or decreases the net stiffness if it is a tensile or compressive type respectively. In this paper, we investigate both these cases by taking two different structures, namely, the micro cantilever beam with gold layer deposited on its top surface and the MEMS gyroscope with residual stresses. First, we carry out experiments to characterize both these structures to find their resonant frequencies. Later, we analytically model those effects and compare them with the experimentally obtained values. Finally, it is found that the analytical models give an error of less than 10% with respect to the experimental results in both the cases.

Large Low-Frequency Fluctuations in the Velocity of a Driven Vortex Lattice in a Single Crystal of 2H-NbSe2 Superconductor

The driven state of a well-ordered flux line lattice in a single crystal of 2H-NbSe2 in the time domain has revealed the presence of substantial fluctuations in velocity, with large and distinct time periods (similar to seconds). A superposition of a periodic drive in the driven vortex lattice causes distinct changes in these fluctuations. We propose that prior to the onset of the peak effect there exists a heretofore unexplored regime of coherent dynamics, with unexpected behavior in velocity fluctuations.

Ultrastructural features of the early secretory pathway in Trichoderma reesei

We have systematically analysed the ultra structure of the early secretory pathway in the Trichoderma reesei hyphae in the wild-type QM6a, cellulase overexpressing Rut-C30 strain and a Rut-C30 transformant BV47 overexpressing a recombinant BiP1-VenusYFP fusion protein with an endoplasmic reticulum (ER) retention signal. The hyphae were studied after 24h of growth using transmission electron microscopy, confocal microscopy and quantitative stereological techniques. All three strains exhibited different spatial organisation of the ER at 24h in both a cellulase-inducing medium and a minimal medium containing glycerol as a carbon source (non-cellulase-inducing medium). The wild-type displayed a number of ER subdomains including parallel tubular/cisternal ER, ER whorls, ER-isolation membrane complexes with abundant autophagy vacuoles and dense bodies. Rut-C30 and its transformant BV47 overexpressing the BiP1-VenusYFP fusion protein also contained parallel tubular/cisternal ER, but no ER whorls; also, there were very few autophagy vacuoles and an increasing amount of punctate bodies where particularly the recombinant BiP1-VenusYFPfusion protein was localised. The early presence of distinct strain-specific features such as the dominance of ER whorls in the wild type and tub/cis ER in Rut-C30 suggests that these are inherent traits and not solely a result of cellular response mechanisms by the high secreting mutant to protein overload.

Spinodal Decomposition in Tellurite-Based Glasses Induced by Excimer Laser Irradiation

Tellurite-based glasses in the TeO2-K3Li2Nb5O15, TeO2-Ba5Li2Ti2Nb8O30, and V2Te2O9 were fabricated by the conventional melt-quenching technique. Amorphous and glassy characteristics of the as-quenched samples were established via the X-ray powder diffraction technique and differential thermal analysis, respectively. The as-quenched samples were irradiated by an excimer laser (248 nm). The effect of laser power, duration of irradiation, and the frequency of the laser pulses on the surface features of the above glasses were studied. The optical microscopic studies carried out on the above systems revealed the presence of quasi-periodic and periodic structures on their surfaces. The local compositional variations of these structures were confirmed by back-scattered electron imaging using scanning electron microscope accompanied by energy-dispersive X-ray analysis. These results were convincing enough to state that the glasses in the present investigations had undergone spinodal decomposition on laser irradiation. The incidence of the interconnected texture of two different phases was observed owing to the quenching effect produced by the heating and cooling cycle of the successive laser pulses. Ring- and line-shaped patterns were also observed, respectively, when the pulse frequency of the laser and the duration of irradiation were increased.

Vocalizations of wild Asian elephants (Elephas maximus): Structural classification and social context

Elephants use vocalizations for both long and short distance communication. Whereas the acoustic repertoire of the African elephant (Loxodonta africana) has been extensively studied in its savannah habitat, very little is known about the structure and social context of the vocalizations of the Asian elephant (Elephas maximus), which is mostly found in forests. In this study, the vocal repertoire of wild Asian elephants in southern India was examined. The calls could be classified into four mutually exclusive categories, namely, trumpets, chirps, roars, and rumbles, based on quantitative analyses of their spectral and temporal features. One of the call types, the rumble, exhibited high structural diversity, particularly in the direction and extent of frequency modulation of calls. Juveniles produced three of the four call types, including trumpets, roars, and rumbles, in the context of play and distress. Adults produced trumpets and roars in the context of disturbance, aggression, and play. Chirps were typically produced in situations of confusion and alarm. Rumbles were used for contact calling within and among herds, by matriarchs to assemble the herd, in close-range social interactions, and during disturbance and aggression. Spectral and temporal features of the four call types were similar between Asian and African elephants.

CFD analysis of high frequency miniature pulse tube refrigerators for space applications with thermal non-equilibrium model

High frequency, miniature, pulse tube cryocoolers are extensively used in space applications because of their simplicity. Parametric studies of inertance type pulse tube cooler are performed with different length-to-diameter ratios of the pulse tube with the help of the FLUENT (R) package. The local thermal non-equilibrium of the gas and the matrix is taken into account for the modeling of porous zones, in addition to the wall thickness of the components. Dynamic characteristics and the actual mechanism of energy transfer in pulse are examined with the help of the pulse tube wall time constant. The heat interaction between pulse tube wall and the oscillating gas, leading to surface heat pumping, is quantified. The axial heat conduction is found to reduce the performance of the pulse tube refrigerator. The thermal non-equilibrium predicts a higher cold heat exchanger temperature compared to thermal equilibrium. The pressure drop through the porous medium has a strong non-linear effect due to the dominating influence of Forchheimer term over that of the linear Darcy term at high operating frequencies. The phase angle relationships among the pressure, temperature and the mass flow rate in the porous zones are also important in determining the performance of pulse tuberefrigerator.

Development of Very High Frequency Damped Sine Wave Generator

In order to protect the critical electronic equipment/system against damped sine transient currents induced into its cables due to transient electromagnetic fields, switching phenomena, platform resonances, etc. it is necessary to provide proper hardening. The hardness assurance provided can be evaluated as per the test CS 116 of MIL STD 461E/F in laboratory by generating & inducing the necessary damped sine currents into the cables of the Equipment Under Test (EUT). The need and the stringent requirements for building a damped sine wave current generator for generation of damped sine current transients of very high frequencies (30 MHz & 100 MHz) have been presented. A method using LC discharge for the generation has been considered in the development. This involves building of extremely low & nearly loss less inductors (about 5 nH & 14 nH) as well as a capacitor & a switch with much lower inductances. A technique for achieving this has been described. Two units (I No for 30 MHz. & 100 MHz each) have been built. Experiments to verify the output are being conducted.

Low loss and frequency (1 kHz-1 MHz) independent dielectric characteristics of 3BaO-3TiO(2)-B2O3 glasses

X-ray powder diffraction along with differential thermal analysis carried out on the as-quenched samples in the 3BaO-3TiO(2)-B2O3 system confirmed their amorphous and glassy nature, respectively. The dielectric constants in the 1 kHz-1 MHz frequency range were measured as a function of temperature (323-748 K). The dielectric constant and loss were found to be frequency independent in the 323-473 K temperature range. The temperature coefficient of dielectric constant was estimated using Havinga's formula and found to be 16 ppm K-1. The electrical relaxation was rationalized using the electric modulus formalism. The dielectric constant and loss were 17 +/- 0.5 and 0.005 +/- 0.001, respectively at 323 K in the 1 kHz-1 MHz frequency range which may be of considerable interest to capacitor industry.

Assessment of motivation to control alcohol use: The motivational thought frequency and state motivation scales for alcohol control

Introduction The Elaborated Intrusion Theory of Desire holds that desires for functional and dysfunctional goals share a common form. Both are embodied cognitive events, characterised by affective intensity and frequency. Accordingly, we developed scales to measure motivational cognitions for functional goals (Motivational Thought Frequency, MTF; State Motivation, SM), based on the existing Craving Experience Questionnaire (CEQ). When applied to increasing exercise, MTF and SM showed the same three-factor structure as the CEQ (Intensity, Imagery, Availability). The current study tested the internal structure and concurrent validity of the MTF and SM Scales when applied to control of alcohol consumption (MTF-A; SM-A). Methods Participants (N = 417) were adult tertiary students, staff or community members who had recently engaged in high-risk drinking or were currently trying to control alcohol consumption. They completed an online survey comprising the MTF-A, SM-A, Alcohol Use Disorders Identification Test (AUDIT), Readiness to Change Questionnaire (RCQ) and demographics. Results Confirmatory Factor Analysis gave acceptable fit for the MTF-A, but required the loss of one SM-A item, and was improved by intercorrelations of error terms. Higher scores were associated with more severe problems on the AUDIT and with higher Contemplation and Action scores on the RCQ. Conclusions The MTF-A and SM-A show potential as measures of motivation to control drinking. Future research will examine their predictive validity and sensitivity to change. The scales' application to both increasing functional and decreasing dysfunctional behaviours is consistent with EI Theory's contention that both goal types operate in similar ways.

Neurological manifestations and molecular genetics of acute intermittent porphyria in North Western Russia

Acute intermittent porphyria (AIP, MIM #176000) is an inherited metabolic disease due to a partial deficiency of the third enzyme, hydroxymethylbilane synthase (HMBS, EC: 4.3.1.8), in the haem biosynthesis. Neurological symptoms during an acute attack, which is the major manifestation of AIP, are variable and relatively rare, but may endanger a patient's life. In the present study, 12 Russian and two Finnish AIP patients with severe neurological manifestations during an acute attack were studied prospectively from 1995 to 2006. Autonomic neuropathy manifested as abdominal pain (88%), tachycardia (94%), hypertension (75%) and constipation (88%). The most common neurological sign was acute motor peripheral neuropathy (PNP, 81%) often associated with neuropathic sensory loss (54%) and CNS involvement (85%). Despite heterogeneity of the neurological manifestations in our patients with acute porphyria, the major pattern of PNP associated with abdominal pain, dysautonomia, CNS involvement and mild hepatopathy could be demonstrated. If more strict inclusion criteria for biochemical abnormalities (>10-fold increase in excretion of urinary PBG) are applied, neurological manifestations in an acute attack are probably more homogeneous than described previously, which suggests that some of the neurological patients described previously may not have acute porphyria but rather secondary porphyrinuria. Screening for acute porphyria using urinary PBG is useful in a selected group of neurological patients with acute PNP or encephalopathy and seizures associated with pain and dysautonomia. Clinical manifestations and the outcome of acute attacks were used as a basis for developing a 30-score scale of the severity of an acute attack. This scale can easily be used in clinical practice and to standardise the outcome of an attack. Degree of muscle weakness scored by MRC, prolonged mechanical ventilation, bulbar paralysis, impairment of consciousness and hyponatraemia were important signs of a poor prognosis. Arrhythmia was less important and autonomic dysfunction, severity of pain and mental symptoms did not affect the outcome. The delay in the diagnosis and repeated administrations of precipitating factors were the main cause of proceeding of an acute attack into pareses and severe CNS involvement and a fatal outcome in two patients. Nerve conduction studies and needle EMG were performed in eleven AIP patients during an acute attack and/or in remission. Nine patients had severe PNP and two patients had an acute encephalopathy but no clinically evident PNP. In addition to axonopathy, features suggestive of demyelination could be demonstrated in patients with severe PNP during an acute attack. PNP with a moderate muscle weakness was mainly pure axonal. Sensory involvement was common in acute PNP and could be subclinical. Decreased conduction velocities with normal amplitudes of evoked potentials during acute attacks with no clinically evident PNP indicated subclinical polyneuropathy. Reversible symmetrical lesions comparable with posterior reversible encephalopathy syndrome (PRES) were revealed in two patients' brain CT or MRI during an acute attack. In other five patients brain MRI during or soon after the symptoms was normal. The frequency of reversible brain oedema in AIP is probably under-estimated since it may be short-lasting and often indistinguishable on CT or MRI. In the present study, nine different mutations were identified in the HMBS gene in 11 unrelated Russian AIP patients from North Western Russia and their 32 relatives. AIP was diagnosed in nine symptom-free relatives. The majority of the mutations were family-specific and confirmed allelic heterogeneity also among Russian AIP patients. Three mutations, c.825+5G>C, c.825+3_825+6del and c.770T>C, were novel. Six mutations, c.77G>A (p.R26H), c.517C>T (p.R173W), c.583C>T (p.R195C), c.673C>T (p.R225X), c.739T>C (p.C247R) and c.748G>C (p.E250A), have previously been identified in AIP patients from Western and other Eastern European populations. The effects of novel mutations were studied by amplification and sequencing of the reverse-transcribed total RNA obtained from the patients' lymphoblastoid or fibroblast cell lines. The mutations c.825+5G>C and c.770T>C resulted in varyable amounts of abnormal transcripts, r.822_825del (p.C275fsX2) and [r.770u>c, r.652_771del, r.613_771del (p.L257P, p.G218_L257del, p.I205_L257del)]. All mutations demonstrated low residual activities (0.1-1.3 %) when expressed in COS-1 cells confirming the causality of the mutations and the enzymatic defect of the disease. The clinical outcome, prognosis and correlation between the HMBS genotype and phenotype were studied in 143 Finnish and Russian AIP patients with ten mutations (c.33G>T, c.97delA, InsAlu333, p.R149X, p.R167W, p.R173W, p.R173Q, p.R225G, p.R225X, c.1073delA) and more than six patients in each group. The patients were selected from the pool of 287 Finnish AIP patients presented in a Finnish Porphyria Register (1966-2003) and 23 Russian AIP patients (diagnosed 1995-2003). Patients with the p.R167W and p.R225G mutations showed lower penetrance (19% and 11%) and the recurrence rate (33% and 0%) in comparison to the patients with other mutations (range 36 to 67% and 0 to 66%, respectively), as well as milder biochemical abnormalities [urinary porphobilinogen 47±10 vs. 163±21 mol/L, p<0.001; uroporphyrin 130±40 vs. 942±183 nmol/L, p<0.001] suggesting a milder form of AIP in these patients. Erythrocyte HMBS activity did not correlate with the porphobilinogen excretion in remission or the clinical of the disease. In all AIP severity patients, normal PBG excretion predicted freedom from acute attacks. Urinary PBG excretion together with gender, age at the time of diagnosis and mutation type could predict the likelihood of acute attacks in AIP patients.

Platinum dendritic nanoparticles with magnetic behavior

Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.