Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

L-Arginyl-L-Glutamic Acid Dihydrate, C11h21n5o5.2h2o

M r = 339.35, monoclinic, P2 t, a = 11.028 (2), b=9.583 (2), c= 16.010 (2) A, fl= 96.57 (1) °, U= 1680.85 A 3, Z = 4, D m = 1.37, D x= 1.34 Mg m -3, Cu Ka, 2 = 1.54184 A, p = 0.85 mm -1, F(000)=728, T=300K, R=0.085 for 2845 diffractometer- measured reflections IF o > 3cr(Fo)]. The two molecules in the asymmetric unit have similar conformations except for a static disorder at the C ~ and C ~ positions in one of the glutamic-acid side chains. An interesting feature of the crystal structure is a pair of hydrogen bonds between the guanidinium and ycarboxylate groups of neighbouring molecules. This is the first such specific interaction observed between side chains of arginine and glutamic acid.

A Survey Of Software Dependability

This paper presents on overview of the issues in precisely defining, specifying and evaluating the dependability of software, particularly in the context of computer controlled process systems. Dependability is intended to be a generic term embodying various quality factors and is useful for both software and hardware. While the developments in quality assurance and reliability theories have proceeded mostly in independent directions for hardware and software systems, we present here the case for developing a unified framework of dependability—a facet of operational effectiveness of modern technological systems, and develop a hierarchical systems model helpful in clarifying this view. In the second half of the paper, we survey the models and methods available for measuring and improving software reliability. The nature of software “bugs”, the failure history of the software system in the various phases of its lifecycle, the reliability growth in the development phase, estimation of the number of errors remaining in the operational phase, and the complexity of the debugging process have all been considered to varying degrees of detail. We also discuss the notion of software fault-tolerance, methods of achieving the same, and the status of other measures of software dependability such as maintainability, availability and safety.

Byzantine-resilient distributed computing systems

This paper is aimed at reviewing the notion of Byzantine-resilient distributed computing systems, the relevant protocols and their possible applications as reported in the literature. The three agreement problems, namely, the consensus problem, the interactive consistency problem, and the generals problem have been discussed. Various agreement protocols for the Byzantine generals problem have been summarized in terms of their performance and level of fault-tolerance. The three classes of Byzantine agreement protocols discussed are the deterministic, randomized, and approximate agreement protocols. Finally, application of the Byzantine agreement protocols to clock synchronization is highlighted.

Fault tolerance in multiprocessor systems

Multiprocessor systems which afford a high degree of parallelism are used in a variety of applications. The extremely stringent reliability requirement has made the provision of fault-tolerance an important aspect in the design of such systems. This paper presents a review of the various approaches towards tolerating hardware faults in multiprocessor systems. It. emphasizes the basic concepts of fault tolerant design and the various problems to be taken care of by the designer. An indepth survey of the various models, techniques and methods for fault diagnosis is given. Further, we consider the strategies for fault-tolerance in specialized multiprocessor architectures which have the ability of dynamic reconfiguration and are suited to VLSI implementation. An analysis of the state-óf-the-art is given which points out the major aspects of fault-tolerance in such architectures.

Performance modelling of a fault-tolerant real-time multiprocessor using stochastic Petri nets

The fault-tolerant multiprocessor (ftmp) is a bus-based multiprocessor architecture with real-time and fault- tolerance features and is used in critical aerospace applications. A preliminary performance evaluation is of crucial importance in the design of such systems. In this paper, we review stochastic Petri nets (spn) and developspn-based performance models forftmp. These performance models enable efficient computation of important performance measures such as processing power, bus contention, bus utilization, and waiting times.

Structure of N-[bis(methylthio)methylene]cinnamamide, C12H13NOS2

M r = 251.34, monoclinic, P21/n, a =14.626 (3), b= 7.144 (1), c= 11.996 (2)\AA \betat=90.03 (2) °, V= 1253.4 (6) \AA 3, Z = 4, Dm= 1.326 (3),Dx=1.331(3)gcm -3, MoKat, \lambda = 0.7107 )\AA , \mu=3.51 cm -3, F(000) = 528.0, T-- 293 K, R -- 3.5% for1455 significant reflections. Of particular interest is an intramolecular attractive interaction between the sulphur and oxygen atoms with an S...O distance of 2.658 (3)\AA, in which the oxygen atom appears to actas a nucleophile.

3,3',5,5'-Tetrabromophenolsulfonphthalein (bromphenol blue), C19H10Br4O5S

M r=670.02, monoclinic, C2/c, a= 31.003(4), b=11.037(2), c=21.183(3)A, fl= 143.7 (1) °, V= 4291.2/k 3, D,n = 2.06, D x = 2.07Mgm -3, Z=8, MoKa, 2=0.7107/k, /~=7.45 mm -1, F(000) = 2560, T= 293 K, R = 0.061 for 1697 observed reflections. The bromphenol blue molecule consists essentially of three planar groupings: the sulfonphthalein ring system and two dibromophenol rings attached to the tetrahedral C atom of the five-membered ring of the sulfonphthalein system. The dibromophenol rings are inclined with resPect to each other at 73 ° whereas they make angles of 85 and 68 ° with respect to the sulfonphthalein system. The molecules aggregate into helical columns with the non-polar regions of the molecules in the interior and the polar regions on the surface. The columns are held together by a network of hydrogen bonds.

4-Biphenylyl phenyl thioketone (I), C19H14S, and 1-naphthyl phenyl thioketone (II), C17H12S

(I): Mr=274"39, orthorhombic, Pbca, a = 7.443 (1), b= 32.691 (3), c= 11.828 (2)A, V= 2877.98A 3, Z=8, Din= 1.216 (flotation in KI), D x = 1.266 g cm -3, /~(Cu Ka, 2 = 1.5418 A) = 17.55 cm -1, F(000) = li52.0, T= 293 K, R = 6.8%, 1378 significant reflections. (II): M r = 248.35, orthorhombic, P212~21, a = 5.873 (3), b = 13.677 (3), c = 15-668 (5) A, V = 1260.14 A 3, Z = 4, D,n = 1.297 (flotation in KI), Dx= 1.308 g cm -a, /t(CuKa, 2=1.5418 A) = 19.55 cm -~, F(000) = 520.0, T= 293 K, R = 6.9%, 751 significant reflections. Crystals of (I) and (II) undergo photo-oxidation in the crystallinestate. In (I) the dihedral angle between the phenyl rings of the biphenyl moiety is 46 (1) °. The C=S bond length is 1.611(5) A in (I) and 1.630 (9)/~ in (II). The correlation between molecular packing and reactivity is discussed.

The Structure of Monosodium Phosphoenolpyruvate

CDH406P-.Na +.H20 , M r = 208.0, is monoclinic, Cc, a = 11.423 (2), b = 23.253 (5), c - 6.604 (1) A, fl = 123.63 (1) °, U = 1460.6 A 3, D x =. 1.89 Mg m -a, Z = 8, 2(Mo Ka) = 0.7107 A, p(Mo Ka) = 0.44 mm -~, F(000) = 840. Final R = 0.063 for 1697 reflections.The two crystallographically independent molecules of phosphoenolpyruvate (PEP) (A and B) are almost mirror images of each other, the mirror being the planar enolpyruvate group. The torsion angle C(3)-C(2)- O(1)-P(1) is 122.6 in A and -112.0 ° in B, in contrast to -209.1 ° in PEP.K. The enolic C(2)-O(1) has a partial double-bond character [1.401 (A), 1.386A (B)]. The high-energy P~O bond (1.595 and 1.610A) is comparable to that in PEP.K (1.612 A). Na(1) has six nearest neighbours while Na(2) has only five. The Na + ions are involved in binding only the phosphates of different molecules, in contrast to the K ÷ ion in PEP. K, which binds to both the phosphate and carboxyl ends of the same molecule. The planar carboxyl groups stack on each other at an average distance of 3.2 A instead of forming hydrogen-bonded dimers usually found in carboxylate structures.

Sustainable development indicators : Much wanted, less used?

For the past twenty years, several indicator sets have been produced on international, national and regional levels. Most of the work has concentrated on the selection of the indicators and on collection of the pertinent data, but less attention has been given to the actual users and their needs. This dissertation focuses on the use of sustainable development indicator sets. The dissertation explores the reasons that have deterred the use of the indicators, discusses the role of sustainable development indicators in a policy-cycle and broadens the view of use by recognising three different types of use. The work presents two indicator development processes: The Finnish national sustainable development indicators and the socio-cultural indicators supporting the measurement of eco-efficiency in the Kymenlaakso Region. The sets are compared by using a framework created in this work to describe indicator process quality. It includes five principles supported by more specific criteria. The principles are high policy relevance, sound indicator quality, efficient participation, effective dissemination and long-term institutionalisation. The framework provided a way to identify the key obstacles for use. The two immediate problems with current indicator sets are that the users are unaware of them and the indicators are often unsuitable to their needs. The reasons for these major flaws are irrelevance of the indicators to the policy needs, technical shortcomings in the context and presentation, failure to engage the users in the development process, non-existent dissemination strategies and lack of institutionalisation to promote and update the indicators. The importance of the different obstacles differs among the users and use types. In addition to the indicator projects, materials used in the dissertation include 38 interviews of high-level policy-makers or civil servants close to them, statistics of the national indicator Internet-page downloads, citations of the national indicator publication, and the media coverage of both indicator sets. According to the results, the most likely use for a sustainable development indicator set by policy-makers is to learn about the concept. Very little evidence of direct use to support decision-making was available. Conceptual use is also common for other user groups, namely the media, civil servants, researchers, students and teachers. Decision-makers themselves consider the most obvious use for the indicators to be the promotion of their own views which is a form of legitimising use. The sustainable development indicators have different types of use in the policy cycle and most commonly expected instrumental use is not very likely or even desirable at all stages. Stages of persuading the public and the decision-makers about new problems as well as in formulating new policies employ legitimising use. Learning by conceptual use is also inherent to policy-making as people involved learn about the new situation. Instrumental use is most likely in policy formulation, implementation and evaluation. The dissertation is an article dissertation, including five papers that are published in scientific journals and an extensive introductory chapter that discusses and weaves together the papers.

Substance flow analysis in Finland : Four case studies on N and P flows

Nitrogen (N) and phosphorus (P) are essential elements for all living organisms. However, in excess, they contribute to several environmental problems such as aquatic and terrestrial eutrophication. Globally, human action has multiplied the volume of N and P cycling since the onset of industrialization. The multiplication is a result of intensified agriculture, increased energy consumption and population growth. Industrial ecology (IE) is a discipline, in which human interaction with the ecosystems is investigated using a systems analytical approach. The main idea behind IE is that industrial systems resemble ecosystems, and, like them, industrial systems can then be described using material, energy and information flows and stocks. Industrial systems are dependent on the resources provided by the biosphere, and these two cannot be separated from each other. When studying substance flows, the aims of the research from the viewpoint of IE can be, for instance, to elucidate the ways how the cycles of a certain substance could be more closed and how the flows of a certain substance could be decreased per unit of production (= dematerialization). In Finland, N and P are studied widely in different ecosystems and environmental emissions. A holistic picture comparing different societal systems is, however, lacking. In this thesis, flows of N and P were examined in Finland using substance flow analysis (SFA) in the following four subsystems: I) forest industry and use of wood fuels, II) food production and consumption, III) energy, and IV) municipal waste. A detailed analysis at the end of the 1990s was performed. Furthermore, historical development of the N and P flows was investigated in the energy system (III) and the municipal waste system (IV). The main research sources were official statistics, literature, monitoring data, and expert knowledge. The aim was to identify and quantify the main flows of N and P in Finland in the four subsystems studied. Furthermore, the aim was to elucidate whether the nutrient systems are cyclic or linear, and to identify how these systems could be more efficient in the use and cycling of N and P. A final aim was to discuss how this type of an analysis can be used to support decision-making on environmental problems and solutions. Of the four subsystems, the food production and consumption system and the energy system created the largest N flows in Finland. For the creation of P flows, the food production and consumption system (Paper II) was clearly the largest, followed by the forest industry and use of wood fuels and the energy system. The contribution of Finland to N and P flows on a global scale is low, but when compared on a per capita basis, we are one of the largest producers of these flows, with relatively high energy and meat consumption being the main reasons. Analysis revealed the openness of all four systems. The openness is due to the high degree of internationality of the Finnish markets, the large-scale use of synthetic fertilizers and energy resources and the low recycling rate of many waste fractions. Reduction in the use of fuels and synthetic fertilizers, reorganization of the structure of energy production, reduced human intake of nutrients and technological development are crucial in diminishing the N and P flows. To enhance nutrient recycling and replace inorganic fertilizers, recycling of such wastes as wood ash and sludge could be promoted. SFA is not usually sufficiently detailed to allow specific recommendations for decision-making to be made, but it does yield useful information about the relative magnitude of the flows and may reveal unexpected losses. Sustainable development is a widely accepted target for all human action. SFA is one method that can help to analyse how effective different efforts are in leading to a more sustainable society. SFA's strength is that it allows a holistic picture of different natural and societal systems to be drawn. Furthermore, when the environmental impact of a certain flow is known, the method can be used to prioritize environmental policy efforts.

Peptide-lanthanide interactions. Crystal structure of a europium(III)-triglycine complex

Crystals of Eu-(Gly-Gly-Gly).(H2O)5.(ClO4)3 are triclinic, spacegroup P1BAR with a = 9.123 (2), b = 11.185 (5), c = 11.426 (2) angstrom; alpha = 90.79 (2), beta = 98.08 (1), gamma = 98.57 (2)-degrees; Z = 2. The europium cation is surrounded by four oxygens from three different peptide units and four oxygens from water molecules. The geometry around the metal is a distorted bi-capped trigonal prism. The peptide backbone conformation in this complex is compared with those in the free peptide and in various metal complexes. Considerable differences are observed between Eu(III) and Ca(II) complexes of triglycine. (C) Munksgaard 1994.

Asiakastietojärjestelmän muutos lakisääteisessä lastensuojelun sosiaalityössä - jännitteistä toimijuutta

Tämän pro gradu -tutkielman tarkoituksena on ollut tavoittaa niitä vaikutuksia, joita tietojärjestelmien käytöllä on sosiaali- ja terveysalalla. Tarkastelu sijoittuu lastensuojelun sosiaalityöhön. Yhden toimintayksikön tapahtumien kuvaus ja analyysi on puheenvuoro, jolla olen pyrkinyt tavoittamaan yhteyksiä tietojärjestelmien käyttöön liittyviin yleisiin ilmiöihin. Tutkielma on tiheä kuvaus lastensuojelun sosiaalityöstä asiakastietojärjestelmän muutosvaiheessa. Tapahtumia on jäsennetty toimijuuden käsitteen kautta (Archer 2003, Heiskala, 2000). Sosiaalityöntekijän toimijuus on ollut keskiössä tutkimussuunnitelman mukaisesti. Asiakastietojärjestelmä työntyi muutosvaiheessa toimijan rooliin vaikuttaen muun muassa lastensuojelun sosiaalityön työprosesseihin. Tietojärjestelmän toimijuus vaikuttaa sosiaalityöntekijään toimijana ja työntekijän toimijan asemaan. Aineistosta nousi teoretisoinnin (Layder, 1998) kautta esille jännitteisyys näiden keskeisten toimijoiden välillä. Jännite jäsentyi kolmelle kentälle. Lainsäädännön kenttä sulkee sisäänsä organisaatiota ja sosiaalityöntekijän perustehtävää kuvaavat kentät. Kenttien sisällöissä havaitsin yhtäläisyyttä Heiskalan (2000) yhteiskunnallisia pakkoja koskevaan jaotteluun. Pakot välittyvät semioottisesti tarkastellen merkkien eli lakimerkkien, rahamerkkien ja rituaalisesti vahvistettujen symbolien välityksellä. Tutkielman aineiston pohjalta on analysoitavaksi noussut kysymys uuden julkisjohtamisen (NPM) (Harvey, 2006, Julkunen, 2006) vaikutuksista lastensuojelun sosiaalityössä. Uuden julkisjohtamisen elementit tuottavat toimintaan jännitteitä edellä kuvatuilla kolmella kentällä. Yhtä toimintayksikköä koskeva aineisto antaa viitteitä siitä, että NPM toimii lastensuojelun sosiaalityössä toimintaa ohjaavana käyttöteoriana. Käyttöteorian (Argyris & Schön, 1996) käsitteellä ymmärretään yksilön tai organisaation todellista toimintaa ohjaavaa teoriaa, mikä voi olla ristiriidassa julkilausuttujen toiminnan teorioiden kanssa. Yksilö tai organisaatio ei välttämättä ole tietoinen käyttöteorian ja julkilausutun teorian välisestä kuilusta, minkä esiin saaminen edellyttäisi reflektiota. Tutkimuskohteena on ollut Helsingin kaupungin sosiaaliviraston ruotsinkielisiä lastensuojelun palveluja tuottava yksikkö. Tutkimuksen aineisto on kerätty uuden asiakastietojärjestelmän käyttöönottovaiheessa 1.11.2008–28.2.2009. Menetelmällisesti tutkimus sijoittuu toimintatutkimukselliseen kehykseen (Carr & Kemmis, 1986). Kenttävaiheen aikana yhdistin tutkijan ja toimijan roolit työskennellen sosiaalityöntekijänä tutkimukseni kohteena olleessa yksikössä. Kirjallinen aineisto koostuu järjestelmämuutosta koskevista päätöksistä, tiedotteista ja ohjeista. Järjestelmän muutosvaiheessa kokosin aineistoa osallistuvan havainnoinnin menetelmällä. Aineistossa on mukana myös yksikön työntekijöiden kanssa tuotettua materiaalia muutosvaiheen aikaisten sisältöjen haltuun ottamiseksi, esimerkiksi työn prosessikuvauksia. Aineisto on analysoitu sisällönanalyysillä. Analyysin edetessä kävin jäsennyksistäni keskustelua toimintayksikön työntekijöiden kanssa. Tapaamisten jälkeen jatkoin analyysiä ja teoretisointia käyttäen semioottista sosiologiaa metateoriana ja aktanttimallia muutosvaihetta kuvaavien kertomusten koostamisessa. Kertomusten pohjalta jatkoin toimijuuden analyysiä subjektiaseman (Törrönen, 2000) ja toimijan aseman (Alasuutari 2007) käsitteitä käyttäen.

Crystal structure of 8-methoxy-3-dibromoacetylcoumarin, C12H8Br2O4

C12H8BT2O4. monoclinic, P12(1)/cl (No. 14), a = 11.546(2) Angstrom, b = 6.885(4) Angstrom,= 15.949(3) Angstrom, beta = 101.75(2)degrees, V= 1241.3 Angstrom(3), Z = 4, p(m) = 2.040 g.cm(-3), R-all(F) = 0.039, wR(all)(F) = 0.043, T = 300 K.