Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Kunnossapidon kehitysmalli sanomalehtipainon tuotannon luotettavuuden, tuottavuuden ja tuotteen laadun turvaamiseksi

Diplomityössä käsitellään ne toimet, jotka Esa Lehtipaino Oy:ssä tarvitsee tehdä kunnossapidon kehittämiseksi sanomalehtipainoprosessin kunnossapidossa. Työssä käytettiin luotettavuuskeskeisen ja kokonaisvaltaisen tuottavuuskeskeisen kunnossapidon strategioiden osia sekä PSK Standardisoinnin PSK 5705:2006standardin mukaista menetelmää määrittämään kunnossapidon kannalta tärkeimmät kohteet ja osa-alueet. PSK 5705:2006 on kunnonvalvonnan värähtelymittausten mittaustoiminnan suunnitteluun luotu standardi, jonka perusteella rakennettiin sanomalehtipainoprosessiin sopiva tuotantolaitteiston luokitusjärjestelmä. Luokituksenperusteella kohdennetaan kunnossapidon resurssit tuotantojärjestelmän luotettavuuden kannalta oikeisiin, tuottavimpiin kohteisiin. Tuotantohenkilöstön kunnossapitohenkilökunnalle tekemien vikailmoitusten välitykseen rakennettiin Microsoft Access -pohjainen Vikaloki-lomake. Kunnossapitotoiminnan kehityksen tuloksien seuraamiseksi määritettiin PSK 6201:2003 standardin mukainen tuotannon kokonaistehokkuutta kuvaava KNL-luku. KNL-luvusta luotiin ennuste kunnossapidon kehittämistarpeista regressioanalyysin avulla. Kehitysmalli esittää, että kohdeyrityksessä tulee toiminnan kehittäminen aloittaa päivittämällä tietokonepohjainen toiminnanohjausjärjestelmä, johon lisätään ennakoivat suunnitellut kunnossapitotoimet. Toimet määriteltiin yllämainitun kriittisyysluokituksen perusteella.

1000 V distribution system and its potential in Russia

The application of the three voltage level 20/1/0.4 distribution system in Finland has proved to be an economic solution to enhance the reability of electricity distribution. By using 1 kV voltage level between medium and low voltage networks, the improvement in reability could be reached especially inaerial lines networks. Also considerable savings in investment and outage costscould be archieved compared to the traditional distribution system. This master's thesis is focused on the describing the situation in Russian distribution netwoks and consequent analyses the possibility of applying 1000V distribution system in Russia. The goal is to investigate on the basis of Finnish experience is any possible installation targets in Russia for the new system. Compatibility with Russian safety and quality standards are also studied in this thesis.

A microarray-based system for the simultaneous analysis of single nucleotide polymorphisms in human genes involved in the metabolism of anti-malarial drugs

Background: In order to provide a cost-effective tool to analyse pharmacogenetic markers in malaria treatment, DNA microarray technology was compared with sequencing of polymerase chain reaction (PCR) fragments to detect single nucleotide polymorphisms (SNPs) in a larger number of samples. Methods: The microarray was developed to affordably generate SNP data of genes encoding the human cytochrome P450 enzyme family (CYP) and N-acetyltransferase-2 (NAT2) involved in antimalarial drug metabolisms and with known polymorphisms, i.e. CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and NAT2. Results: For some SNPs, i.e. CYP2A6*2, CYP2B6*5, CYP2C8*3, CYP2C9*3/*5, CYP2C19*3, CYP2D6*4 and NAT2*6/*7/*14, agreement between both techniques ranged from substantial to almost perfect (kappa index between 0.61 and 1.00), whilst for other SNPs a large variability from slight to substantial agreement (kappa index between 0.39 and 1.00) was found, e. g. CYP2D6*17 (2850C>T), CYP3A4*1B and CYP3A5*3. Conclusion: The major limit of the microarray technology for this purpose was lack of robustness and with a large number of missing data or with incorrect specificity.

CleanEx: a database of heterogeneous gene expression data based on a consistent gene nomenclature and linked to an improved annotation system

Résumé: L'automatisation du séquençage et de l'annotation des génomes, ainsi que l'application à large échelle de méthodes de mesure de l'expression génique, génèrent une quantité phénoménale de données pour des organismes modèles tels que l'homme ou la souris. Dans ce déluge de données, il devient très difficile d'obtenir des informations spécifiques à un organisme ou à un gène, et une telle recherche aboutit fréquemment à des réponses fragmentées, voir incomplètes. La création d'une base de données capable de gérer et d'intégrer aussi bien les données génomiques que les données transcriptomiques peut grandement améliorer la vitesse de recherche ainsi que la qualité des résultats obtenus, en permettant une comparaison directe de mesures d'expression des gènes provenant d'expériences réalisées grâce à des techniques différentes. L'objectif principal de ce projet, appelé CleanEx, est de fournir un accès direct aux données d'expression publiques par le biais de noms de gènes officiels, et de représenter des données d'expression produites selon des protocoles différents de manière à faciliter une analyse générale et une comparaison entre plusieurs jeux de données. Une mise à jour cohérente et régulière de la nomenclature des gènes est assurée en associant chaque expérience d'expression de gène à un identificateur permanent de la séquence-cible, donnant une description physique de la population d'ARN visée par l'expérience. Ces identificateurs sont ensuite associés à intervalles réguliers aux catalogues, en constante évolution, des gènes d'organismes modèles. Cette procédure automatique de traçage se fonde en partie sur des ressources externes d'information génomique, telles que UniGene et RefSeq. La partie centrale de CleanEx consiste en un index de gènes établi de manière hebdomadaire et qui contient les liens à toutes les données publiques d'expression déjà incorporées au système. En outre, la base de données des séquences-cible fournit un lien sur le gène correspondant ainsi qu'un contrôle de qualité de ce lien pour différents types de ressources expérimentales, telles que des clones ou des sondes Affymetrix. Le système de recherche en ligne de CleanEx offre un accès aux entrées individuelles ainsi qu'à des outils d'analyse croisée de jeux de donnnées. Ces outils se sont avérés très efficaces dans le cadre de la comparaison de l'expression de gènes, ainsi que, dans une certaine mesure, dans la détection d'une variation de cette expression liée au phénomène d'épissage alternatif. Les fichiers et les outils de CleanEx sont accessibles en ligne (http://www.cleanex.isb-sib.ch/). Abstract: The automatic genome sequencing and annotation, as well as the large-scale gene expression measurements methods, generate a massive amount of data for model organisms. Searching for genespecific or organism-specific information througout all the different databases has become a very difficult task, and often results in fragmented and unrelated answers. The generation of a database which will federate and integrate genomic and transcriptomic data together will greatly improve the search speed as well as the quality of the results by allowing a direct comparison of expression results obtained by different techniques. The main goal of this project, called the CleanEx database, is thus to provide access to public gene expression data via unique gene names and to represent heterogeneous expression data produced by different technologies in a way that facilitates joint analysis and crossdataset comparisons. A consistent and uptodate gene nomenclature is achieved by associating each single gene expression experiment with a permanent target identifier consisting of a physical description of the targeted RNA population or the hybridization reagent used. These targets are then mapped at regular intervals to the growing and evolving catalogues of genes from model organisms, such as human and mouse. The completely automatic mapping procedure relies partly on external genome information resources such as UniGene and RefSeq. The central part of CleanEx is a weekly built gene index containing crossreferences to all public expression data already incorporated into the system. In addition, the expression target database of CleanEx provides gene mapping and quality control information for various types of experimental resources, such as cDNA clones or Affymetrix probe sets. The Affymetrix mapping files are accessible as text files, for further use in external applications, and as individual entries, via the webbased interfaces . The CleanEx webbased query interfaces offer access to individual entries via text string searches or quantitative expression criteria, as well as crossdataset analysis tools, and crosschip gene comparison. These tools have proven to be very efficient in expression data comparison and even, to a certain extent, in detection of differentially expressed splice variants. The CleanEx flat files and tools are available online at: http://www.cleanex.isbsib. ch/.

Effluent particle removal by microirrigation system filters

La distribución del número y del volumen de partículas, y la eficiencia de eliminación de las partículas y los sólidos en suspensión de diferentes efluentes y sus filtrados, fueron analizadas para estudiar si los filtros más usuales en los sistemas de riego localizado eliminan las partículas que pueden obturar los goteros. En la mayoría de los efluentes y filtrados fue mínimo el número de partículas con diámetros superiores a 20 μm. Sin embargo, al analizar la distribución del volumen de las partículas, en los filtrados aparecieron partículas de dimensiones superiores a la luz de los filtros de anillas y malla, siendo el filtro de arena el que retuvo las partículas de mayor diámetro. La eficiencia de los filtros para retener partículas se debió más al tipo de efluente que al filtro. Se verificó también que la distribución del número de partículas sigue una relación de tipo potencial. Analizando el exponente β de la ley potencial, se halló que los filtros no modificaron significativamente la distribución del número de partículas de los efluentes.

Elicitation of subjective crop yield PDF

En este trabajo se investiga la coherencia y confiabilidad de estimaciones de funciones de densidad de probabilidad (FDP) subjetivas de rendimientos de cultivos realizadas por un amplio grupo de agricultores. Se utilizaron tres técnicas de elicitación diferentes: el método de estimación de FDP en dos pasos, la distribución Triangular y la distribución Beta. Los sujetos entrevistados ofrecieron estimaciones para los valores puntuales de rendimientos de cultivos (medio, máximo posible, más frecuente y mínimo posible) y para las FDP basadas en la estimación de intervalos. Para evaluar la persistencia, se utilizaron los conceptos de persistencia temporal y persistencia metodológica. Los resultados son interesantes para juzgar la adecuación de las técnicas de estimación de probabilidades subjetivas a los sistemas de ayuda en la toma de decisiones en agricultura.

Short communication. Persistence of point crop yield subjective estimates

En este trabajo se investiga la persistencia de las estimaciones puntuales subjetivas de rendimientos en cultivos anua- les realizadas por un amplio grupo de agricultores. La persistencia en el tiempo es una condición necesaria para la co- herencia y la confiabilidad de las estimaciones subjetivas de variables aleatorias. Los sujetos entrevistados estimaron valores puntuales de rendimientos de cultivos anuales (rendimientos medio, mayor, mínimo y más frecuente). Se han encontrado diferencias relativas poco importantes en todas las variables, excepto en los rendimientos mínimos, donde existe una alta dispersión. Los resultados son interesantes para estimar la adecuación de las técnicas de estimación de probabilidades subjetivas para ser utilizadas en los sistemas de ayuda en la toma de decisiones en agricultura.

Design of User Authentication System for Multi-operator wireless LANs

Langattomat lähiverkot ovat viime vuosikymmeninä saavuttaneet suuren suosion. Tässä työssä käsitellään käyttäjien todentamisjärjestelmän suunnittelua ja kehitystä langattomaan monioperaattoriverkkoon. Langattomassa monioperaattoriverkossa käyttäjillä on mahdollisuus käyttää eri operaattoreiden palveluita. Aluksi käsitellään olemassa olevia todentamismenetelmiä ja -järjestelmiä. minkä jälkeen kuvaillaan todentamisjärjestelmä langattomille monioperaattoriverkoille. Todentamisjärjestelmän ratkaisuvaihtoehtoja esitellään kaksi, niin sanotut moni- istunto - ja yksittäisistuntomalli. Moni-istuntomalli on normaali lähestymistapa käyttäjien todentamiseen tietokonejärjestelmissä. Siinä käyttäjän pitää tunnistautua ja todentaa itsensä jokaiselle verkon palvelulle erikseen. Yksittäisistuntomallissa pyritään parempaan luotettavuuteen ja käytettävyyteen. Siinä käyttäjä todentaa itsensä vain kerran ja voi sen jälkeen päästä useisiin palveluihin. Työn loppuosassa kuvaillaan suunnitellun järjestelmän toteutusta. Lisäksi ehdotetaan vaihtoehtoisia toteutustapoja, analysoidaan järjestelmän heikkouksia ja kerrotaan jatkokehitysmahdoillisuuksista.

Long-term X-ray variability of the microquasar system LS5039/RX J1826.2-1450

We report on the results of the spectral and timing analysis of a BeppoSAX observation of the microquasar system LS 5039/RX J1826.2-1450. The source was found in a low-flux state with Fx(1-10 keV)= 4.7 x 10^{-12} erg cm^{-2} s^{-1}, which represents almost one order of magnitude lower than a previous RXTE observation 2.5 years before. The 0.1--10 keV spectrum is described by an absorbed power-law continuum with photon-number spectral index Gamma=1.8+-0.2 and hydrogen column density of NH=1.0^{+0.4}_{-0.3} x 10^{22} cm^{-2}. According to the orbital parameters of the system the BeppoSAX observation covers the time of an X-ray eclipse should one occur. However, the 1.6-10 keV light curve does not show evidence for such an event, which allows us to give an upper limit to the inclination of the system. The low X-ray flux detected during this observation is interpreted as a decrease in the mass accretion rate onto the compact object due to a decrease in the mass-loss rate from the primary.

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms.

BACKGROUND: Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM: Our aim was to challenge the validity of these software algorithms. METHODS: We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS: In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. CONCLUSION: We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes. Pediatr Pulmonol. 2015; 50:970-977. © 2015 Wiley Periodicals, Inc.

Reliability of maximal grip strength measurements and grip strength recovery following a stroke.

STUDY DESIGN: Clinical measurement. PURPOSE: The test-retest reliability of maximal grip strength measurements (MGSM) is examined in subjects for 12 weeks post-stroke together with maximal grip strength recovery and the maximal-grip and upper-extremity strength measurements' relationship with capacity and performance test scores. METHODS: A Jamar dynamometer and the Motricity Index (MI) were used for strength measurements. The Chedoke Arm and Hand Activity Inventory and ABILHAND questionnaire for evaluating capacities and performances. RESULTS: MGSM were reliable (Intraclass Correlation Coefficients = 0.97-0.99, Minimal Detectable Differences = 2.73-4.68 kg). Among the 34 participants, 47% did not have a measurable grip strength one week post-stroke but 50% of these recovered some strength within the first eight weeks. The MGSM and MI scores were correlated with scores of tests of capacity and performance (Spearman's Rank Correlation Coefficients = 0.69-0.94). CONCLUSIONS: MGSM are reliable in the first weeks after a stroke. LEVEL OF EVIDENCE: N/A.

Choosing a platform for a billing system

Enterprises have a need in use of billing. Before actual choose of a billing system an appropriate platform has to be deployed. This work presents a study of a platform choosing for a billing system and shows the role of optimally chosen platform. In evaluation of a platform several criteria were considered: cost, scalability, reliability, safety, usability, portability and efficiency. In the thesis three different platforms MAC OS, Linux and MS Windows were studied. The results of the evaluation of each platform are shown and according to this results the most suitable platform for a billing system was chosen.

System Investigation for Hybrid Electric Vehicle

A hybrid electric vehicle is a fast-growing concept in the field of vehicle industry. Nowadays two global problems make manufactures to develop such systems. These problems are: the growing cost of a fuel and environmental pollution. Also development of controlled electric drive with high control accuracy and reliability allows improving of vehicle drive characteristics. The objective of this Diploma Thesis is to investigate the possibilities of electrical drive application for new principle of parallel hybrid vehicle system. Electric motor calculations, selection of most suitable control system and other calculations are needed. This work is not final work for such topic. Further investigation with more precise calculations, modeling, measurements and cost calculations are needed to answer the question if such system is efficient.