Genome-wide association study of prostate cancer-specific survival

BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). RESULTS: We observed no significant association between genetic variants and prostate cancer survival. CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study. IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Studies on the Cell Wall Structure and on the Mechanical Properties of Norway Spruce

The structure and the mechanical properties of wood of Norway spruce (Picea abies [L.] Karst.) were studied using small samples from Finland and Sweden. X-ray diffraction (XRD) was used to determine the orientation of cellulose microfibrils (microfibril angle, MFA), the dimensions of cellulose crystallites and the average shape of the cell cross-section. X-ray attenuation and x-ray fluorescence measurements were used to study the chemical composition and the trace element content. Tensile testing with in situ XRD was used to characterise the mechanical properties of wood and the deformation of crystalline cellulose within the wood cell walls. Cellulose crystallites were found to be 192 284 Å long and 28.9 33.4 Å wide in chemically untreated wood and they were longer and wider in mature wood than in juvenile wood. The MFA distribution of individual Norway spruce tracheids and larger samples was asymmetric. In individual cell walls, the mean MFA was 19 30 degrees, while the mode of the MFA distribution was 7 21 degrees. Both the mean MFA and the mode of the MFA distribution decreased as a function of the annual ring. Tangential cell walls exhibited smaller mean MFA and mode of the MFA distribution than radial cell walls. Maceration of wood material caused narrowing of the MFA distribution and removed contributions observed at around 90 degrees. In wood of both untreated and fertilised trees, the average shape of the cell cross-section changed from circular via ambiguous to rectangular as the cambial age increased. The average shape of the cell cross-section and the MFA distribution did not change as a result of fertilisation. The mass absorption coefficient for x-rays was higher in wood of fertilised trees than in that of untreated trees and wood of fertilised trees contained more of the elements S, Cl, and K, but a smaller amount of Mn. Cellulose crystallites were longer in wood of fertilised trees than in that of untreated trees. Kraft cooking caused widening and shortening of the cellulose crystallites. Tensile tests parallel to the cells showed that if the mean MFA is initially around 10 degrees or smaller, no systematic changes occur in the MFA distribution due to strain. The role of mean MFA in defining the tensile strength or the modulus of elasticity of wood was not as dominant as that reported earlier. Crystalline cellulose elongated much less than the entire samples. The Poisson ratio νca of crystalline cellulose in Norway spruce wood was shown to be largely dependent on the surroundings of crystalline cellulose in the cell wall, varying between -1.2 and 0.8. The Poisson ratio was negative in kraft cooked wood and positive in chemically untreated wood. In chemically untreated wood, νca was larger in mature wood and in latewood compared to juvenile wood and earlywood.

Good Lives, Hidden Miseries : An Ethnography of Uncertainty in a Finnish Village

This is an ethnographic study, in the field of medical anthropology, of village life among farmers in southwest Finland. It is based on 12 months of field work conducted 2002-2003 in a coastal village. The study discusses how social and cultural change affects the life of farmers, how they experience it and how they act in order to deal with the it. Using social suffering as a methodological approach the study seeks to investigate how change is related to lived experiences, idioms of distress, and narratives. Its aim has been to draw a locally specific picture of what matters are at stake in the local moral world that these farmers inhabit, and how they emerge as creative actors within it. A central assumption made about change is that it is two-fold; both a constructive force which gives birth to something new, and also a process that brings about uncertainty regarding the future. Uncertainty is understood as an existential condition of human life that demands a response, both causing suffering and transforming it. The possibility for positive outcomes in the future enables one to understand this small suffering of everyday life both as a consequence of social change, which fragments and destroys, and as an answer to it - as something that is positively meaningful. Suffering is seen to engage individuals to ensure continuity, in spite of the odds, and to sustain hope regarding the future. When the fieldwork was initiated Finland had been a member of the European Union for seven years and farmers felt it had substantially impacted on their working conditions. They complained about the restrictions placed on their autonomy and that their knowledge was neither recognised, nor respected by the bureaucrats of the EU system. New regulations require them to work in a manner that is morally unacceptable to them and financial insecurity has become more prominent. All these changes indicate the potential loss of the home and of the ability to ensure continuity of the family farm. Although the study initially focused on getting a general picture of working conditions and the nature of farming life, during the course of the fieldwork there was repeated mention of a perceived high prevalence of cancer in the area. This cancer talk is replete with metaphors that reveal cultural meanings tied to the farming life and the core values of autonomy, endurance and permanence. It also forms the basis of a shared identity and a means of delivering a moral message about the fragmentation of the good life; the loss of control; and the invasion of the foreign. This thesis formed part of the research project Expressions of Suffering. Ethnographies of Illness Experiences in Contemporary Finnish Contexts funded by the Academy of Finland. It opens up a vital perspective on the multiplicity and variety of the experience of suffering and that it is particularly through the use of the ethnographic method that these experiences can be brought to light. Keywords: suffering, uncertainty, phenomenology, habitus, agency, cancer, farming

Samarbete genom lagstiftning. Samarbetsförfarandets organisation, procedur och innehåll

Samarbetslagen är en omstridd lag. Innan lagen trädde i kraft i början av år 1979 fanns på arbetstagarsidan förhoppningar om att skapa en lag om reell företagsdemokrati medan man från arbetsgivarhåll var rädd att personalen skulle få ett alltför stort inflytande på beslutsfattandet. En oro fanns också att medbestämmandet skulle byråkratisera beslutsfattandet inom företagen. I dag anser många arbetstagare att samarbetsförfarandet endast används vid massuppsägningar, nedskärningar och rationaliseringar men i övrigt glömts bort. Samarbetsförfarandet och regleringen av det är en viktig och aktuell fråga, eftersom samarbetsförfarandet utgör det forum i samarbetet mellan arbetsgivare och personal där nedskärningar och massuppsägningar diskuteras. Avhandlingens syfte är att analysera hur samarbetsförfarandet fungerar utifrån samarbetslagen. Målet är att granska samarbetsförfarandet ur ett perspektiv där samarbetsförfarandet ses som en potentiell möjlighet och ett verktyg till framgångsrik företagsverksamhet och personalledarskap. I analysen utgår författaren från samarbetslagens 1 §. Syftet med samarbetsförfarandet är att utveckla företagets verksamhet och arbetsförhållanden, att effektivera samarbetet mellan arbetsgivare och personal samt personalens interna samverkan. Samarbetsförfarandet skall utöka personalens möjligheter att påverka behandlingen av ärenden som gäller deras arbete och arbetsplats i enlighet med lagen. Enligt samarbetsförfarandet skall arbetsgivaren rådgöra med arbetstagarna och deras företrädare om de viktigaste ärendena som påverkar personalens ställning och arbetsförhållande innan besluten fattas. Avhandlingen granskar hur lagen tillämpas i dag och hur lagstiftningen kan utvecklas för att effektivera samarbetet i framtiden.

Optical Tweezers for Single Molecule Biology

Molecular machinery on the micro-scale, believed to be the fundamental building blocks of life, involve forces of 1-100 pN and movements of nanometers to micrometers. Micromechanical single-molecule experiments seek to understand the physics of nucleic acids, molecular motors, and other biological systems through direct measurement of forces and displacements. Optical tweezers are a popular choice among several complementary techniques for sensitive force-spectroscopy in the field of single molecule biology. The main objective of this thesis was to design and construct an optical tweezers instrument capable of investigating the physics of molecular motors and mechanisms of protein/nucleic-acid interactions on the single-molecule level. A double-trap optical tweezers instrument incorporating acousto-optic trap-steering, two independent detection channels, and a real-time digital controller was built. A numerical simulation and a theoretical study was performed to assess the signal-to-noise ratio in a constant-force molecular motor stepping experiment. Real-time feedback control of optical tweezers was explored in three studies. Position-clamping was implemented and compared to theoretical models using both proportional and predictive control. A force-clamp was implemented and tested with a DNA-tether in presence of the enzyme lambda exonuclease. The results of the study indicate that the presented models describing signal-to-noise ratio in constant-force experiments and feedback control experiments in optical tweezers agree well with experimental data. The effective trap stiffness can be increased by an order of magnitude using the presented position-clamping method. The force-clamp can be used for constant-force experiments, and the results from a proof-of-principle experiment, in which the enzyme lambda exonuclease converts double-stranded DNA to single-stranded DNA, agree with previous research. The main objective of the thesis was thus achieved. The developed instrument and presented results on feedback control serve as a stepping stone for future contributions to the growing field of single molecule biology.

A detailed chemistry multi-cycle simulation of a gasoline fueled HCCI engine operated with NVO

A previously developed Stochastic Reactor Model (SRM) is used to simulate combustion in a four cylinder in-line four-stroke naturally aspirated direct injection Spark Ignition (SI) engine modified to run in Homogeneous Charge Compression Ignition (HCCI) mode with a Negative Valve Overlap (NVO). A portion of the fuel is injected during NVO to increase the cylinder temperature and enable HCCI combustion at a compression ratio of 12:1. The model is coupled with GT-Power, a one-dimensional engine simulation tool used for the open valve portion of the engine cycle. The SRM is used to model in-cylinder mixing, heat transfer and chemistry during the NVO and main combustion. Direct injection is simulated during NVO in order to predict heat release and internal Exhaust Gas Recycle (EGR) composition and mass. The NOx emissions and simulated pressure profiles match experimental data well, including the cyclic fluctuations. The model predicts combustion characteristics at different fuel split ratios and injection timings. The effect of fuel reforming on ignition timing is investigated along with the causes of cycle to cycle variations and unstable operation. A detailed flux analysis during NVO unearths interesting results regarding the effect of NOx on ignition timing compared with its effect during the main combustion. © 2009 SAE International.

Experimental investigation of a control method for SI-HCCI-SI transition in a multi-cylinder gasoline engine

In HCCI engines, the Air/Fuel Ratio (AFR) and Residual Gas Fraction (RGF) are difficult to control during the SI-HCCI-SI transition, and this may result in incomplete combustion and/or high pressure raise rates. As a result, there may be undesirably high engine load fluctuations. The objectives of this work are to further understand this process and develop control methods to minimize these load fluctuations. This paper presents data on instantaneous AFR and RGF measurements, both taken by novel experimental techniques. The data provides an insight into the cyclic AFR and RGF fluctuations during the switch. These results suggest that the relatively slow change in the intake Manifold Air Pressure (MAP) and actuation time of the Variable Valve Timing (VVT) are the main causes of undesired AFR and RGF fluctuations, and hence an unacceptable Net IMEP (NIMEP) fluctuation. We also found large cylinder-to-cylinder AFR variations during the transition. Therefore, besides throttle opening control and VVT shifting, cyclic and individual cylinder fuel injection control is necessary to achieve a smooth transition. The control method was developed and implemented in a test engine, and the result was a considerably reduced NIMEP fluctuation during the mode switch. The instantaneous AFR and RGF measurements could furthermore be adopted to develop more sophisticated control methods for SI-HCCI-SI transitions. © 2010 SAE International.

Modelling soot formation in a DISI engine

In this work, the formation of soot in a Direct Injection Spark Ignition (DISI) engine is simulated using the Stochastic Reactor Model (SRM) engine code. Volume change, convective heat transfer, turbulent mixing, direct injection and flame propagation are accounted for. In order to simulate flame propagation, the cylinder is divided into an unburned, entrained and burned zone, with the rate of entrainment being governed by empirical equations but combustion modelled with chemical kinetics. The model contains a detailed chemical mechanism as well as a highly detailed soot formation model, however computation times are relatively short. The soot model provides information on the morphology and chemical composition of soot aggregates along with bulk quantities, including soot mass, number density, volume fraction and surface area. The model is first calibrated by simulating experimental data from a Gasoline Direct Injection (GDI) Spark Ignition (SI) engine. The model is then used to simulate experimental data from the literature, where the numbers, sizes and derived mass particulate emissions from a 1.83 L, 4-cylinder, 4 valve production DISI engine were examined. Experimental results from different injection and spark timings are compared with the model and the qualitative trends in aggregate size distribution and emissions match the exhaust gas measurements well. © 2010 The Combustion Institute. Published by Elsevier Inc. All rights reserved.

Morenitas y ratonas.

En aguas dulces del Centro y Sud América se encuentran los gimnótidos, familia de peces estrictamente acantonados en esa zona. De las treinta especies que la constituyen, doce se ecuentran en Manaos o alrededores, siendo nuestro Río de la Plata el límite sur de la distribución de este singular grupo. (PDF tiene 12 paginas.)

Europäische Fischerei in afrikanischen Gewässern - Information über die Fischerei in Mauretanien

Die mauretanische Atlantikküste ist rund 700 km lang. Der Küste vorgelagert ist ein ca. 30 bis 120, im Mittel 50 km breiter Schelf, von insgesamt 34 000 km2, wenn man die 200-m-Tiefenlinie als Schelfgrenze zugrundelegt. Dieses Schelfgebiet liegt im Bereich des nordost-atlantischen Auftriebs. Aufsteigende, kalte und sauerstoffreiche Tiefenwasser führen dort zu einer hohen Primärproduktion. Das bedeutet gute Nahrungsbedingungen für eine vielfältige und reichhaltige Fauna mit hoher Reproduktionsfähigkeit. Das bedeutet gleichzeitig ideale Bedingungen für eine vielfältige und ertragreiche Fischerei. So ist die Fischerei auch neben dem Eisenerzabbau die wichtigste wirtschaftlichen Grundlage für das Land. Das Forschungsinstitut in Nouadhibou, der zweitgrößten Stadt des Landes, schätzt das Fischereipotential innerhalb der Wirtschaftszone auf über 1 Mill. Tonnen, wovon ca. 80 % auf pelagische Arten entfallen. Die unmittelbare Nutzung der Ressourcen durch die einheimische Fischerei spielte bisher nur eine kleine Rolle. Zwar ändert sich das in dem Maße wie die Bevölkerungszahl zunimmt, aber immer noch werden die größeren Anteile der fischbaren Reserven an ausländische Fischereien vergeben, gegen Lizenzgebühren, versteht sich. Einer der Vertragspartner Mauretaniens ist die Europäische Union. Seit dem 1. August 1996 ist ein Fischereiabkommen in Kraft, das der Union Fischereirechte an bestimmten Arten einräumt. Dieses Abkommen gilt zunächst für 5 Jahre, kann aber um jeweils den gleichen Zeitraum erweitert werden. Es soll hier umrissen werden, wie sich dieser Vertrag in die biologischen, fischereilichen, sozialen und politischen Bedingungen des Landes einfügt.

Die Neustrukturierung der Übereinkommen zum Schutz der Meeresumwelt des Nordostatlantiks und der Ostsee

Das am 16. November 1994 in Kraft getretene Seerechtsübereinkommen der Vereinten Nationen (United Nations Convention on the Law of the Sea) regelt völkerrechtlich alle Nutzungsarten der Meere. Die dort erlassenen Vorschriften beschränken sich auf allgemeine Rechtsgrundsätze, seerechtliche Kompetenzregelungen und Staatenverpflichtungen zum Erlaß internationaler und nationaler Regelungen. Das Vertragswerk bezieht den marinen Umweltschutz, einen Kernbereich globaler Umweltpolitik, ausdrücklich mit ein. Wesentlich konkreter in der Umsetzung umweltpolitischer Ziele sind die internationalen Übereinkommen zum Schutz der Meeresumwelt. Für den in Abbildung 1 gezeigten Teil des Nordostatlantiks einschließlich der Nordsee existieren derartige Übereinkommen bereits seit 1972 durch das OSLO und PARIS Übereinkommen und für die gesamte Ostsee seit 1974 durch das HELSINKI Übereinkommen. Im Lichte des heutigen Umweltverständnisses und unter Berücksichtigung des weiterentwickelten Seerechts wurden beide Übereinkommen 1992 neu gefaßt. Die politischen Veränderungen haben insbesondere im Ostseeraum auch zu geographischen Erweiterungen geführt. Die mit der Novellierung der jeweiligen Übereinkommen verbundene Neuorganisation ist weiterhin selbstverständlich von den Erfahrungen aus der zwanzigjährigen Überwachungstätigkeit und dem in dieser Zeit durch die Meeresforschung gewachsenen Wissen geprägt.

Fraccionamiento del licor gastado en pasteado al sulfito ácido mediante ultrafiltración

Lignosulphonates (LS) and fermentable sugars are the main components of spent sulphite liquors (SSL) produced in acid sulphite pulping. In spite of different methods have been used for spent liquor fractionation such as precipitation or vaporization; membrane technology allows the separation of these components from the SSL due to their different size molecular weight, offering great advantages with regards to the traditionally methods (less energy consumption, high selective separation, and many others). In the present study, ceramic membranes with different cut-offs (15 kDa, 5 kDa and 1 kDa) were used to achieve the sugar purification and the LS concentration. The membranes were evaluated according to their efficacy and efficiency properties. Different series system were tested in order to improve the aptitudes of a singular membrane. The system with the three membranes in series (15, 5 and 1 kDa respectively) obtained the most purified permeate stream, referred to the sugar content. Also, a characterisation of the LS contained in the different streams produced in this system was carried out in order to know in a more precise manner the valorisation potential of these components by means of biorefinery processes.

利用反义RNA技术进行木质素生物合成调控的研究

木质素是一类酚类次生代谢产物，在植物体内行使重要的生理功能，但它却是形成造纸污染的主要来源。利用基因工程手段，在分子水平调节木质素的生物合成，降低木质素的含量或改变组分以培育适合造纸的植物原料树种具有较大的应用价值和环保效益。本研究利用反义RNA技术，主要围绕木质素合成三种相关酶咖啡酸-O-甲基转移酶（COMT）、咖啡酰辅酶A-O-甲基转移酶(CCoAOMT)、4-香豆酸：辅酶A连接酶（4CL）的基因对植物木质素生物合成途径调节的研究，取得如下进展： 1.农杆菌介导法将COMT和CCoAOMT基因的单价和双价的反义表达载体导入烟草，比较了两个甲基化酶的功能。PCR-Southern和Northern点杂交结果表明反义基因已整合到烟草基因组DNA上，并在转录水平表达。两种反义基因对木质素生物合成调节的效果显示，CCoAOMT能更有效地调节木质素生物总量的合成，COMT仅特异调节S木质素的合成。表达反义CCoAOMT基因的转基因毛白杨，内源CCoAOMT基因的表达在转录和蛋白水平均受到抑制，最终引起转基因植株木质素含量普遍降低，最多降低达26.20%，筛选出木质素含量下降10%以上的转基因毛白杨株系8个，为源头治理造纸废水污染奠定了基础。 2． 对克隆的4CL基因进行了表达特性分析， RT-PCR分析表明，分离的毛白杨4CL基因主要在木质部丰富表达，叶中表达量较少，树皮中不表达。在毛白杨的一个生长季，该基因表达显示明显的双锋特征，该表达模式与木材早材和晚材的发育时期相吻合，表明分离的毛白杨4CL基因与木质素的生物合成密切相关。农杆菌介导法将反义4CL基因导入烟草和毛白杨，利用分子生物学检测手段对转化植株进行筛选，获得批量转基因植株。Klason木质素含量测定分析表明，抑制内源4CL基因表达，能有效降低转基因植物中的木质素含量，且不影响植株正常生长和发育以及碳水化合物的合成。转基因毛白杨的茎杆上一些区域呈红棕色，颜色的深度与转基因毛白杨木质素含量的下降幅度呈一定的正相关性，颜色变化可作为转基因植株筛选的一个辅助指标。现已获得木质素含量下降10%以上的转基因株系3个，最多下降达41.73%，可供中试与制浆实验，为培育低木质素环保型毛白杨提供理论与实践依据。 3.为了优化现有的表达框架，使目的基因更有效地调节木质素的生物合成，应用PCR技术从毛白杨基因组中分离得到C4H(肉桂酸4—羟基化酶)基因启动子片段（GenBank注册号：AY351673）。GUS荧光活性分析和组织化学染色显示，该启动子在一些木质化的组织和器官中特异表达，随着组织成熟度和木质化程度的增加，表达活性逐渐增强，并且该启动子受伤诱导。反义CCoAOMT基因在C4H启动子的调控下，会引起转基因烟草木质素均有不同程度的减少，但不影响碳向碳水化合物的转换合成，对植物的生长发育也无明显负效应。这些结果证明了从毛白杨中分离的C4H 启动子可以应用于造纸原料树种材性改良的遗传工程操作。 4．首次从水稻中华10号（Oryza sativa L. ssp. japonica）分离了CCoAOMT基因家族的三个成员，对其基因结构及表达特性的分析表明，该基因家族的三个成员与水稻的木质化进程关系密切，研究结果有助于了解单子叶植物中的甲基化途径发生机制，为高产水稻抗倒伏和茎杆饲料作物的遗传改良奠定了基础。