Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.

Evolution, Homology Conservation, and Identification of Unique Sequence Signatures in GH19 Family Chitinases

The discovery of GH (Glycoside Hydrolase) 19 chitinases in Streptomyces sp. raises the possibility of the presence of these proteins in other bacterial species, since they were initially thought to be confined to higher plants. The present study mainly concentrates on the phylogenetic distribution and homology conservation in GH19 family chitinases. Extensive database searches are performed to identify the presence of GH19 family chitinases in the three major super kingdoms of life. Multiple sequence alignment of all the identified GH19 chitinase family members resulted in the identification of globally conserved residues. We further identified conserved sequence motifs across the major sub groups within the family. Estimation of evolutionary distance between the various bacterial and plant chitinases are carried out to better understand the pattern of evolution. Our study also supports the horizontal gene transfer theory, which states that GH19 chitinase genes are transferred from higher plants to bacteria. Further, the present study sheds light on the phylogenetic distribution and identifies unique sequence signatures that define GH19 chitinase family of proteins. The identified motifs could be used as markers to delineate uncharacterized GH19 family chitinases. The estimation of evolutionary distance between chitinase identified in plants and bacteria shows that the flowering plants are more related to chitinase in actinobacteria than that of identified in purple bacteria. We propose a model to elucidate the natural history of GH19 family chitinases.

Identification, estimation and preparation of fatty acids by circular paper chromatography

A comparatively simple and rapid method for the identification, estimation and preparation of fatty acids has been developed, using reversed phase circular paper chromatography. The method is also suitable for the analysis of “Critical Pairs” of fatty acids and for the preparation of fatty acids. Further, when used at a higher temperature, the method is more sensitive in revealing the presence of even traces of higher fatty acids in the seeds of Adenanthera pavonina.

Tyttöjen kesken : Monikulttuurisuus ja sukupuolten tasa-arvo nuorisotyössä.

Among Girls Youth Work, Multiculturalism and Gender Equality Finland s increasingly multicultural society concerns younger generations in a very particular manner. Starting already in pre-school kindergartens, children from different cultural backgrounds share their everyday existence. The focus of this study is Finland s increasingly multicultural society that has challenged youth work professionals in particular and made them rethink questions related to content, basic values and goals of youth work. These reconsiderations include the following essential questions: which of these pedagogic principles are defined as Finnish, and under what kinds of circumstances would the youth workers be ready to negotiate about them. These questions, which are related to multiculturalism, are then linked to the girls position, status and gender equality. The research examines how gender equality is articulated in relation to multiculturalism and vice versa, in what contexts youth work-related questions are negoatiated in, and how these negotiations then relate to gender issues. The present study combines theoretical concepts and debates from both post-colonial and youth research, and has benefited greatly from previous research which has examined the everyday lives of young people with multicultural backgrounds and conceptualised the different meanings of age, ethnicity, culture and gender. Neither multiculturalism nor gender equality is, however, taken as a given concept in this study; rather the research focuses on how youth workers understand and define these concepts and how they are used. The emphasis has been on monitoring the varying consequences of different understandings and definitions in terms of everyday work and practices. The goal of this study has been to find typical ways of conceptualising multiculturalism, gender equality and the role of girls in the context of youth work. The focus of the research is not just the youth workers different views but also the notions of the girls themselves. These are then further analysed by examining the ways the girls negotiate their agency. Examples of how the girls agency is defined and the different forms of agency that are offered to the girls within the context of leisure time activities and youth work have been sought. The kind of agency the girls then assume is also examined. The data in this research is comprised of interviews with young people with multicultural backgrounds (n=39), youth workers (n=42) and of ethnographic fieldwork (2003 2005). The fieldwork concentrated on following different types of youth work activities that were targeted at girls with migrant backgrounds. These were organized both by selected municipalities and NGOs. The research shows that various questions related to multicultural issues have enhanced the visibility of gender equality in the field of youth work. The identification of gender-based inequality is especially closely linked to the position of girls from migrant backgrounds. These girls are a source of particular worry and the aim of the many activity groups for migrant girls is to educate them so that they can become equal Finnish citizens . The youth work itself is seen as gender-neutral and equality based. Equality in this context is defined as a purely quantitative concept, and the solution to any possible inequalities is thus the exact same treatment for everyone . The girls themselves seem mainly confused by the role that is offered to them. They would need a voice and the possibility to have an impact on the planning of youth work activities. They want to have their views heard. The role of the victim assigned to them is very confining and makes it difficult to act. At the same time the research shows how gender-sensitive youth work is seen to mean youth work with girls. Gender-sensitive work with boys is not really done or is done very little, even if many of the interviewees are of the opinion that the true materialization of gender equality would require boys to be taken into account too. The principle of gender equality should be shared by the entire youth work profession. Keywords Youth work, equality, multiculturalism, gender sensitivity, agency, girls, young people, sexuality

A particle filtering approach for structural system identification in vehicle–structure interaction problems

The problem of identification of parameters of a beam-moving oscillator system based on measurement of time histories of beam strains and displacements is considered. The governing equations of motion here have time varying coefficients. The parameters to be identified are however time invariant and consist of mass, stiffness and damping characteristics of the beam and oscillator subsystems. A strategy based on dynamic state estimation method, that employs particle filtering algorithms, is proposed to tackle the identification problem. The method can take into account measurement noise, guideway unevenness, spatially incomplete measurements, finite element models for supporting structure and moving vehicle, and imperfections in the formulation of the mathematical models. Numerical illustrations based on synthetic data on beam-oscillator system are presented to demonstrate the satisfactory performance of the proposed procedure.

Identification of Specific DNA Binding Residues in the TCP Family of Transcription Factors in Arabidopsis

The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an similar to 60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop-helix ( bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors.

Synthesis and identification of a new class of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent antileukemic agents

Benzothiazoles are multitarget agents with broad spectrum of biological activity. Among the antitumor agents discovered in recent years, the identification of various 2-(4-aminophenyl) benzothiazoles as potent and selective antitumor drugs against different cancer cell lines has stimulated remarkable interest. Some of the benzothiazoles are known to induce cell cycle arrest, activation of caspases and interaction with DNA molecule. Based on these interesting properties of benzothiazoles and to obtain new biologically active agents, a series of novel 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives 5(a-i) were synthesized and evaluated for their efficacy as antileukemic agents in human leukemia cells (K562 and Reh). The chemical structures of the synthesized compounds were confirmed by H-1 NMR, LCMS and IR analysis. The cytotoxicity of these compounds were determined using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results showed that, these compounds mediate a significant cytotoxic response to cancer cell lines tested. We found that the compounds having electron withdrawing groups at different positions of the phenyl ring of the thiourea moiety displayed significant cytotoxic effect with IC50 value less than 60 mu M. To rationalize the role of electron withdrawing group in the induction of cytotoxicity, we have chosen molecule 5g (IC50 similar to 15 mu M) which is having chloro substitution at ortho and para positions. Flow cytometric analysis of annexin V-FITC/ propidium iodide (PI) double staining and DNA fragmentation suggest that 5g can induce apoptosis.

Enzyme catalysed non-oxidative decarboxylation of aromatic acids II. Identification of active site residues of 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus niger

In order to understand the mechanism of decarboxylation by 2,3-dihydroxybenzoic acid decarboxylase, chemical modification studies were carried out. Specific modification of the amino acid residues with diethylpyrocarbonate, N-bromosuccinimide and N-ethylmaleiimide revealed that at least one residue each of histidine, tryptophan and cysteine were essential for the activity. Various substrate analogs which were potential inhibitors significantly protected the enzyme against inactivation. The modification of residues at low concentration of the reagents and the protection experiments suggested that these amino acid residues might be present at the active site. Studies also suggested that the carboxyl and ortho-hydroxyl groups of the substrate are essential for interaction with the enzyme.

A new approach for fault location identification in transmission system using stability analysis and SVMs

This paper presents a new approach to the location of fault in the high voltage power transmission system using Support Vector Machines (SVMs). A knowledge base is developed using transient stability studies for apparent impedance swing trajectory in the R-X plane. SVM technique is applied to identify the fault location in the system. Results are presented on sample 3-power station, a 9-bus system illustrate the implementation of the proposed method.

Guessing under source uncertainty with side information

We study the problem of guessing the realization of a finite alphabet source, when some side information is provided, in a setting where the only knowledge the guesser has about the source and the correlated side information is that the joint source is one among a family. We define a notion of redundancy, identify a quantity that measures this redundancy, and study its properties. We then identify good guessing strategies that minimize the supremum redundancy (over the family). The minimum value measures the richness of the uncertainty class.

An intelligent approach using support vector machines for monitoring and identification of faults on transmission systems

Power system disturbances are often caused by faults on transmission lines. When faults occur in a power system, the protective relays detect the fault and initiate tripping of appropriate circuit breakers, which isolate the affected part from the rest of the power system. Generally Extra High Voltage (EHV) transmission substations in power systems are connected with multiple transmission lines to neighboring substations. In some cases mal-operation of relays can happen under varying operating conditions, because of inappropriate coordination of relay settings. Due to these actions the power system margins for contingencies are decreasing. Hence, power system protective relaying reliability becomes increasingly important. In this paper an approach is presented using Support Vector Machine (SVM) as an intelligent tool for identifying the faulted line that is emanating from a substation and finding the distance from the substation. Results on 24-bus equivalent EHV system, part of Indian southern grid, are presented for illustration purpose. This approach is particularly important to avoid mal-operation of relays following a disturbance in the neighboring line connected to the same substation and assuring secure operation of the power systems.

Evolution and decay of cylindrical and spherical nonlinear acoustic waves generated by a sinusoidal source

The present work gives a comprehensive numerical study of the evolution and decay of cylindrical and spherical nonlinear acoustic waves generated by a sinusoidal source. Using pseudospectral and predictor–corrector implicit finite difference methods, we first reproduced the known analytic results of the plane harmonic problem to a high degree of accuracy. The non-planar harmonic problems, for which the amplitude decay is faster than that for the planar case, are then treated. The results are correlated with the known asymptotic results of Scott (1981) and Enflo (1985). The constant in the old-age formula for the cylindrical canonical problem is found to be 1.85 which is rather close to 2, ‘estimated’ analytically by Enflo. The old-age solutions exhibiting strict symmetry about the maximum are recovered; these provide an excellent analytic check on the numerical solutions. The evolution of the waves for different source geometries is depicted graphically.

Comparative study on damage identification from lso-Eigen-Value-Change contours and smeared damage model

The paper proposes two methodologies for damage identification from measured natural frequencies of a contiguously damaged reinforced concrete beam, idealised with distributed damage model. The first method identifies damage from Iso-Eigen-Value-Change contours, plotted between pairs of different frequencies. The performance of the method is checked for a wide variation of damage positions and extents. The method is also extended to a discrete structure in the form of a five-storied shear building and the simplicity of the method is demonstrated. The second method is through smeared damage model, where the damage is assumed constant for different segments of the beam and the lengths and centres of these segments are the known inputs. First-order perturbation method is used to derive the relevant expressions. Both these methods are based on distributed damage models and have been checked with experimental program on simply supported reinforced concrete beams, subjected to different stages of symmetric and un-symmetric damages. The results of the experiments are encouraging and show that both the methods can be adopted together in a damage identification scenario.

Narrowband Detection of Acoustic Source in Shallow Ocean using Vector Sensor Array

The problem of narrowband CFAR (constant false alarm rate) detection of an acoustic source at an unknown location in a range-independent shallow ocean is considered. If a target is present, the received signal vector at an array of N sensors belongs to an M-dimensional subspace if N exceeds the number of propagating modes M in the ocean. A subspace detection method which utilises the knowledge of the signal subspace to enhance the detector performance is presented in thisMpaper. It is shown that, for a given number of sensors N, the performance of a detector using a vector sensor array is significantly better than that using a scalar sensor array. If a target is detected, the detector using a vector sensor array also provides a concurrent coarse estimate of the bearing of the target.