Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders

Brain disorders present a significant burden on affected individuals, their families and society at large. Existing diagnostic tests suffer from a lack of genetic biomarkers, particularly for substance use disorders, such as alcohol dependence (AD). Numerous studies have demonstrated that AD has a genetic heritability of 40-60%. The existing genetics literature of AD has primarily focused on linkage analyses in small family cohorts and more recently on genome-wide association analyses (GWAS) in large case-control cohorts, fueled by rapid advances in next generation sequencing (NGS). Numerous AD-associated genomic variations are present at a common frequency in the general population, making these variants of public health significance. However, known AD-associated variants explain only a fraction of the expected heritability. In this dissertation, we demonstrate that systems biology applications that integrate evolutionary genomics, rare variants and structural variation can dissect the genetic architecture of AD and elucidate its heritability. We identified several complex human diseases, including AD and other brain disorders, as potential targets of natural selection forces in diverse world populations. Further evidence of natural selection forces affecting AD was revealed when we identified an association between eye color, a trait under strong selection, and AD. These findings provide strong support for conducting GWAS on brain disorder phenotypes. However, with the ever-increasing abundance of rare genomic variants and large cohorts of multi-ethnic samples, population stratification becomes a serious confounding factor for GWAS. To address this problem, we designed a novel approach to identify ancestry informative single nucleotide polymorphisms (SNPs) for population stratification adjustment in association analyses. Furthermore, to leverage untyped variants from genotyping arrays – particularly rare variants – for GWAS and meta-analysis through rapid imputation, we designed a tool that converts genotype definitions across various array platforms. To further elucidate the genetic heritability of brain disorders, we designed approaches aimed at identifying Copy Number Variations (CNVs) and viral insertions into the human genome. We conducted the first CNV-based whole genome meta-analysis for AD. We also designed an integrated approach to estimate the sensitivity of NGS-based methods of viral insertion detection. For the first time in the literature, we identified herpesvirus in NGS data from an Alzheimer’s disease brain sample. The work in this dissertation represents a three-faceted advance in our understanding of brain disease etiology: 1) evolutionary genomic insights, 2) novel resources and tools to leverage rare variants, and 3) the discovery of disease-associated structural genomic aberrations. Our findings have broad implications on the genetics of complex human disease and hold promise for delivering clinically useful knowledge and resources

JĒKABPILS DISTRICT, DIGNĀJA PARISH HOMESTEAD FARM "NORIEŠI" DEVELOPMENT OPPORTUNITIES OF GRAIN FARMING PRODUCTION

Jēkabpils district Dignājas parish homestead farm "Norieši" is a small farm specializing in the production of grain and livestock products. The share of small and medium-sized farms is dominant in the number of Latvian rural farms. One of the tasks of the agricultural policy of Latvia is to preserve and motivate the production and integration of small farmers in the market. The aim of the study is to analyze the development possibilities of agricultural production in the homestead farm "Norieši". In the work, the author evaluates the correspondence between the wishes and possibilities of the homestead farm, predicts the further development of the farm

The cost of being landlocked : logistics costs and supply chain reliability

A large proportion of the least developed countries are landlocked and their access to world markets depends on the availability of a trade corridor and transit systems. Based on empirical evidence from World Bank projects and assessments in Africa, Central Asia, and elsewhere, this paper proposes a microeconomic quantitative description of logistics costs. The paper theoretically and empirically highlights that landlocked economies are primarily affected not only by a high cost of freight services but also by the high degree of unpredictability in transportation time. The main sources of costs are not only physical constraints but widespread rent activities and severe flaws in the implementation of the transit systems, which prevent the emergence of reliable logistics services. The business and donor community should push toward implementation of comprehensive facilitation strategies, primarily at the national level, and the design of robust and resilient transport and transit regimes. A better understanding of the political economy of transit and a review of the implementation successes and failures in this area are needed.Transport Economics Policy&Planning,Transport and Trade Logistics,Common Carriers Industry,Economic Theory&Research,Rural Roads&Transport

RECOMMENDATIONS FOR SUSTAINABLE MANAGEMENT OF WOOD RESOURCES IN KRĀSLAVAS DISTRICT

Research work is made in Krāslavas district. The purpose of this work was to carry out Krāslavas district wood resources stock to research and develop recommendations for the sustainable management wood resources in Krāslavas district.: There is newer made those kind of research works for wood stock in Krāslavas district importance of this research work is provided by forestry sector who is one of most important sectors in Krāslavas district This sector provide important Krāslava forestry is one of the leading industries that perform important ecological, economic and social functions, the EU in April 2015 adopted a new EU forestry strategy (COM (2013) 0659), which has offered new guidelines for policy-making in the European sectors closely related to forests. This strategy sets out the main principles of sustainable forest wood management. Krāslavas district needs to take stock wood resources to research and develop recommendations for the sustainable management of wood resources in district

The Casimir Energy Paradox of the QCD String

It is widely thought that the early onset of the asymptotic Casimir energy with unit conformal charge signals bosonic string formation of the confining flux connecting a static quark-antiquark pair in QCD. This is observed on a scale where most of the string eigenmodes do not exist and the few stable modes above the ground state are displaced. Hints for the resolution of this paradox are suggested.Comment: Lattice2003(topology

Supersymmetric Toda Field Theories

We present new supersymmetric extensions of Conformal Toda and $A^{(1)}_N$ Affine Toda field theories. These new theories are constructed using methods similar to those that have been developed to find supersymmetric extensions of two-dimensional bosonic sigma models with a scalar potential. In particular, we show that the Conformal Toda field theory admits a (1,1)-supersymmetric extension, and the $A^{(1)}_N$ Affine Toda field admits a (1,0)-supersymmetric extension.Comment: 13 page

Superconformal Affine Liouville Theory

We present a superconformally invariant and integrable model based on the twisted affine Kac-Moody superalgebra $\hat{osp(2|2)}^{(2)}$ which is the supersymmetrization of the purely bosonic conformal affine Liouville theory recently proposed by Babelon and Bonora. Our model reduces to the super-Liouville or to the super sinh-Gordon theories under certain limit conditions and can be obtained, via hamiltonian reduction, from a superspace WZNW model with values in the corresponding affine KM supergroup. The reconstruction formulae for classical solutions are given. The classical $r$-matrices in the homogeneous grading and the exchange algebras are worked out.Comment: 12 pages, standard Latex file, Bonn Univ. preprint BONN-HE-92-16 (to appear in Phys.Lett.B

Local Attentional Bias Increases Approach Motivation: Evidence from Event-Related Potentials and Frequency Analyses

Over twenty years of research have examined the cognitive consequences of positive affect states, and suggested that positive affect leads to a broadening of cognition. However, this research has primarily examined positive affect that is low in approach motivational intensity (e.g. contentment). In my program of research, I have systematically examined positive affect that varies in approach motivational intensity, and found that positive affect high in approach motivation (e.g. desire) narrow cognition, whereas positive affect low in approach motivation broaden cognition. In this dissertation, I will review past models and present a motivational dimension model of affect that expands understanding of how affective states influence attentional and cognitive breadth. I then review a body of research that has varied the motivational intensity of positive and negative affect and found that affect of low motivational intensity broadens cognitive processes, whereas affect of high motivational intensity narrows cognitive processes. Furthermore, a bi-directional link exists between attentional narrowing and approach motivation, such that a narrowed attentional focus to appetitive stimuli causes greater approach motivation than a broadened attentional focus

QCD String Spectrum 2002

Results from a comprehensive new analysis on the excitation spectrum of the QCD string are presented. A rapid onset of string formation is observed in the spectrum on a length scale of 2 fm, with Dirichlet boundary conditions. The crossover from the short distance spectrum towards string excitations and an observed fine structure in the 1--3 fm range are related to effective string theory. The deficiencies of the Nambu-Goto bosonic string model in describing the observed spectrum are briefly discussed.Comment: Lattice2002(topology), 3 pages, 2 figure

LOGISTICS PERFORMANCE AND EXPORT COMPETITIVENESS: EUROPEAN EXPERIENCE

This article aims to analyse the importance of logistics performance in European Union (EU) exports over a sample period in order to detect possible advances on behalf of Member States. We will estimate several gravity equations using the Logistics Performance Index (LPI) and its components as characteristic proxy variables of trade facilitation. In order to avoid the possible heterogeneity caused by sample bias, we will employ the two-stage model proposed by Heckman. The estimations of the gravity models using the two-stage Heckman model for 26 EU countries lead to the conclusion that logistics were more important for exporting nations than importing nations in both 2005 and 2010, reinforcing the interest in the exporter side of the paper. In reference to the components of the LPI, Competence and Tracking have acquired greater importance in recent years, in keeping with the weak domestic demand in European countries and their search for new international markets.Puertas Medina, RM.; Martí Selva, ML.; Garcia Menendez, L. (2013). LOGISTICS PERFORMANCE AND EXPORT COMPETITIVENESS: EUROPEAN EXPERIENCE. Empirica. 1-14. doi:10.1007/s10663-013-9241-zS114Anderson JE (1979) A theorical foundation to the gravity equation. Am Econ Rev 69: 106–116 http://www.jstor.org/stable/1802501Anderson J, Van Wincoop E (2003) Gravity with gravitas: a solution to the border puzzle. Am Econ Rev 93:170–192. doi: 10.1257/000282803321455214Arvis JF, Mustra M, Ojala L, Shepherd B, Saslavsky D (2007) Connecting to compete: trade logistics in the global economy. World Bank, WashingtonArvis JF, Mustra M, Panzer J, Ojala L, Naula T (2010) Connecting to compete: trade logistics in the global economy. World Bank, WashingtonArvis JF, Mustra M, Ojala L, Shepherd B, Saslavsky D (2012) Connecting to compete: trade logistics in the global economy. World Bank, WashingtonBehar A, Manner P (2008) Logistics and exports. African economics working paper series 293. CSAE WPS/2008-13. University of Oxford, OxfordBehar A, Venables AJ (2010) Transport costs and international trade. In: Palma A, Lindsey R, Quinet E, Vickerman R (eds) Handbook of transport economics. Edward Elgar, pp 97–115Behar A, Manners P, Nelson B (2009) Exports and logistics. Oxford Department of Economics Discussion Paper 439Bergstrand JH (1985) The gravity equation in international trade: some microeconomic foundations and empirical evidence. Rev Econ Stat 71: 143–153. http://www.jstor.org/stable/1925975Bergstrand JH (1989) The generalized gravity equation, monopolistic competition, and the factor-proportions theory in international trade. Rev Econ Stat 67: 474–481. http://www.jstor.org/stable/1928061Breuss F, Egger P (1999) How reliable are estimations of east-west trade potencials based on cross-section gravity analysis? Empirica 26:86–89. doi: 10.1023/A:1007011329676CILT (2012) Available at http://www.ciltuk.org.uk/pages/royalcharter . Accessed 02 Aug 2012Felipe J, Kumar U (2012) The role of trade facilitation in Central Asia: a gravity model. East Eur Econ 50:5–20. doi: 10.2753/EEE0012-875500401Heckman J (1979) Sample selection bias as a specification error. Econometrica 47: 153–161. http://www.jstor.org/stable/1912352Helpman E, Krugman P (1985) Market structure and foreign trade. Increasing returns, imperfect competition and the international economy. The MIT Press, Cambridge, MA/LondonHertel T, Mirza T (2009) The role of trade facilitation in South Asian economic integration. Study on intraregional trade and investment in South Asia. ADB, Mandaluyong CityHollweg C, Wong M-H (2009) Measuring regulatory restrictions in logistics services. ERIA Discussion Paper Series, no. 14Jane C–C (2011) Performance evaluation of logistic systems under cost and reliability considerations. Transp Res E-Log 47:130–137. doi: 10.1016/j.tre.2010.09.012Keskin MH (2012) The exigencies of the common logistics policy for European community and the deconstruction of the common transportation policy. Afr J Bus Manage 6:10697–10707. doi: 10.5897/AJBM11.1523Korinek J, Sourdin P (2011) To what extent are high-quality logistics services trade facilitating? Oecd trade policy working papers 108. OECD PublishingLangley C, Coyle J, Gibson B, Novak R, Bardi E (2008) Managing supply chain: a logistics approach. South–Western College Publishing, LondonMangan J, Lalwani C, Butcher C (2008) Global logistics and supply chain management. Wiley John & Sons, Inc., Hoboken, NJMartí ML, Puertas R, García L (2012) Relevance of trade facilitation in emerging countries′s export. J Int Trade Eco Dev. http://www.tandfonline.com/doi/abs/10.1080/09638199.2012.698639Requena F, Llano C (2010) The border effects in Spain: an industrial-level analysis. Empirica 37:455–476. doi: 10.1007/s10663-010-9123-6Rushton A, Oxley J, Croucher P (2009) The handbook of logistics and distribution management. Kogan Page, LondonVilko J, Karandassov B, Myller E (2011) Logistic infrastructure and its effects on economic development. China–USA Bus Rev 10:1152–1167World Bank (2010) Trade and transport facilitation assessment: a practical toolkit for country implementation. World Bank, Washingto