Prediction of multilocus identity-by-descent

Previous studies have enabled exact prediction of probabilities of identity-by-descent (IBD) in randommating populations for a few loci (up to four or so), with extension to more using approximate regression methods. Here we present a precise predictor of multiple-locus IBD using simple formulas based on exact results for two loci. In particular, the probability of non-IBD X ABC at each of ordered loci A, B, and C can be well approximated by XABC = XABXBC/XB and generalizes to X123. . .k = X12X23. . .Xk-1,k/ Xk-2, where X is the probability of non-IBD at each locus. Predictions from this chain rule are very precise with population bottlenecks and migration, but are rather poorer in the presence of mutation. From these coefficients, the probabilities of multilocus IBD and non-IBD can also be computed for genomic regions as functions of population size, time, and map distances. An approximate but simple recurrence formula is also developed, which generally is less accurate than the chain rule but is more robust with mutation. Used together with the chain rule it leads to explicit equations for non-IBD in a region. The results can be applied to detection of quantitative trait loci (QTL) by computing the probability of IBD at candidate loci in terms of identity-by-state at neighboring markers.

Comparison of two suspension control strategies for multi-axle heavy truck

Two simple and effective control strategies for a multi-axle heavy truck, modified skyhook damping (MSD) control and proportional-integration-derivative (PID) control, were implemented into functional virtual prototype (FVP) model and compared in terms of road friendliness and ride comfort. A four-axle heavy truck-road coupling system model was established using FVP technology and validated through a ride comfort test. Then appropriate passive air suspensions were chosen to replace the rear tandem suspensions of the original truck model for preliminary optimization. The mechanical properties and time lag of dampers were taken into account in simulations of MSD and PID semi-active dampers implemented using MATLAB/Simulink. Through co-simulations with Adams and MATLAB, the effects of semi-active MSD and PID control were analyzed and compared, and control parameters which afforded the best comprehensive performance for each control strategy were chosen. Simulation results indicate that compared with the passive air suspension truck, semi-active MSD control improves both ride comfort and road-friendliness markedly, with optimization ratios of RMS vertical acceleration and RMS tyre force ranging from 10.1% to 44.8%. However, semi-active PID control only reduces vertical vibration of the driver’s seat by 11.1%, 11.1% and 10.9% on A, B and C level roads respectively. Both strategies are robust to the variation of road level.

The structured phase of concurrency

This extended abstract summarizes the state-of-the-art solution to the structuring problem for models that describe existing real world or envisioned processes. Special attention is devoted to models that allow for the true concurrency semantics. Given a model of a process, the structuring problem deals with answering the question of whether there exists another model that describes the process and is solely composed of structured patterns, such as sequence, selection, option for simultaneous execution, and iteration. Methods and techniques for structuring developed by academia as well as products and standards proposed by industry are discussed. Expectations and recommendations on the future advancements of the structuring problem are suggested.

The relationship between airborne small ions and particles in urban environments

Ions play an important role in affecting climate and particle formation in the atmosphere. Small ions rapidly attach to particles in the air and, therefore, studies have shown that they are suppressed in polluted environments. Urban environments, in particular, are dominated by motor vehicle emissions and, since motor vehicles are a source of both particles and small ions, the relationship between these two parameters is not well known. In order to gain a better understanding of this relationship, an intensive campaign was undertaken where particles and small ions of both signs were monitored over two week periods at each of three sites A, B and C that were affected to varying degrees by vehicle emissions. Site A was close to a major road and reported the highest particle number and lowest small ion concentrations. Precursors from motor vehicle emissions gave rise to clear particle formation events on five days and, on each day this was accompanied by a suppression of small ions. Observations at Site B, which was located within the urban airshed, though not adjacent to motor traffic, showed particle enhancement but no formation events. Site C was a clean site, away from urban sources. This site reported the lowest particle number and highest small ion concentration. The positive small ion concentration was 10% to 40% higher than the corresponding negative value at all sites. These results confirm previous findings that there is a clear inverse relationship between small ions and particles in urban environments dominated by motor vehicle emissions.

On structured workflow modelling

While there are many similarities between the languages of the various workflow management systems, there are also significant differences. One particular area of differences is caused by the fact that different systems impose different syntactic restrictions. In such cases, business analysts have to choose between either conforming to the language in their specifications or transforming these specifications afterwards. The latter option is preferable as this allows for a separation of concerns. In this paper we investigate to what extent such transformations are possible in the context of various syntactical restrictions (the most restrictive of which will be referred to as structured workflows). We also provide a deep insight into the consequences, particularly in terms of expressive power, of imposing such restrictions.

Introduction

This book explores the impacts of global economic, political and cultural shifts on various international legal frameworks and legal norms. The economic growth of states throughout Asia, South and Central America and Africa is having a profound effect on the dynamics of international relations, with a resulting impact on the operation and development of international law. This book examines the influence of emerging economies on international legal rules, institutions and processes. It describes recent and predicted changes in economic, political and cultural powers, flowing from the growth of emerging economies such as China, India, Brazil, South Africa and Russia, and analyses the influence of these changes on various legal frameworks and norms. Expert contributors drawn from a variety of fields, including international law, politics, environmental law, human rights, economics and finance, provide a broad analysis of the nature of the shifting global dynamic in its historical and contemporary contexts, and a range of perspectives on the impact of these changes as they relate to specific regimes and issues, including climate change regulation, collective security, indigenous rights, the rights of women and girls, environmental protection and foreign aid and development. The book provides a fresh and comprehensive analysis of an issue with extensive implications for international law and politics.

Dreams and nightmares of alternative powers' futures

This chapter argues the importance of the role and nature of other powers to world order. The author suggests that, if the US are not prepared to take a lead in creating a rules-based legal order, they should and can do so – and it is in their interests to do so. America should be a natural leader in this process, taking part in a global dialogue just as they did in the transatlantic dialogue during the late eighteenth century.

Work environment, job satisfaction, stress and burnout among haemodialysis nurses

Aim To examine the relationships among nurse and work characteristics, job satisfaction, stress, burnout and the work environment of haemodialysis nurses. Background Haemodialysis nursing is characterised by frequent and intense contact with patients in a complex and intense environment. Method Cross-sectional online survey of 417 haemodialysis nurses that included nurse and work characteristics, the Brisbane Practice Environment Measure, Index of Work Satisfaction, Nursing Stress Scale and the Maslach Burnout Inventory. Results Haemodialysis nurses reported an acceptable level of job satisfaction and perceived their work environment positively, although high levels of burnout were found. Nurses who were older and had worked in haemodialysis the longest had higher satisfaction levels, experienced less stress and lower levels of burnout than younger nurses. The in-centre type of haemodialysis unit had greater levels of stress and burnout than home training units. Greater satisfaction with the work environment was strongly correlated with job satisfaction, lower job stress and emotional exhaustion. Conclusion Haemodialysis nurses experienced high levels of burnout even though their work environment was favourable and they had acceptable levels of job satisfaction. Implications for Nursing Management: Targeted strategies are required to retain and avoid burnout in younger and less experienced nurses in this highly specialised field of nursing.

Timing, origin and emplacement dynamics of mass flows offshore of SE Montserrat in the last 110 ka : implications for landslide and tsunami hazards, eruption history, and volcanic island evolution

Mass flows on volcanic islands generated by volcanic lava dome collapse and by larger-volume flank collapse can be highly dangerous locally and may generate tsunamis that threaten a wider area. It is therefore important to understand their frequency, emplacement dynamics, and relationship to volcanic eruption cycles. The best record of mass flow on volcanic islands may be found offshore, where most material is deposited and where intervening hemipelagic sediment aids dating. Here we analyze what is arguably the most comprehensive sediment core data set collected offshore from a volcanic island. The cores are located southeast of Montserrat, on which the Soufriere Hills volcano has been erupting since 1995. The cores provide a record of mass flow events during the last 110 thousand years. Older mass flow deposits differ significantly from those generated by the repeated lava dome collapses observed since 1995. The oldest mass flow deposit originated through collapse of the basaltic South Soufriere Hills at 103-110 ka, some 20-30 ka after eruptions formed this volcanic center. A ∼1.8 km3 blocky debris avalanche deposit that extends from a chute in the island shelf records a particularly deep-seated failure. It likely formed from a collapse of almost equal amounts of volcanic edifice and coeval carbonate shelf, emplacing a mixed bioclastic-andesitic turbidite in a complex series of stages. This study illustrates how volcanic island growth and collapse involved extensive, large-volume submarine mass flows with highly variable composition. Runout turbidites indicate that mass flows are emplaced either in multiple stages or as single events.

EUELC project : a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular - pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARβ genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes. Copyright©ERS Journals Ltd 2009.

Targeting oxidative stress in cancer

Importance of the field: Reactive oxygen species (ROS) occur as natural by-products of oxygen metabolism and have important cellular functions. Normally, the cell is able to maintain an adequate balance between the formation and removal of ROS either via anti-oxidants or through the use specific enzymatic pathways. However, if this balance is disturbed, oxidative stress may occur in the cell, a situation linked to the pathogenesis of many diseases, including cancer. Areas covered in this review: HDACs are important regulators of many oxidative stress pathways including those involved with both sensing and coordinating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by histone deacetylases may play critical roles in cancer progression. What the reader will gain: In this review we discuss the notion that targeting HDACs may be a useful therapeutic avenue in the treatment of oxidative stress in cancer, using chronic obstructive pulmonary disease (COPD), NSCLC and hepatocellular carcinoma (HCC) as examples to illustrate this possibility. Take home message: Epigenetic mechanisms may be an important new therapeutic avenue for targeting oxidative stress in cancer. © 2010 Informa UK, Ltd.

The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.

Monitoring the price and affordability of foods and diets globally

Food prices and food affordability are important determinants of food choices, obesity and non-communicable diseases. As governments around the world consider policies to promote the consumption of healthier foods, data on the relative price and affordability of foods, with a particular focus on the difference between ‘less healthy’ and ‘healthy’ foods and diets, are urgently needed. This paper briefly reviews past and current approaches to monitoring food prices, and identifies key issues affecting the development of practical tools and methods for food price data collection, analysis and reporting. A step-wise monitoring framework, including measurement indicators, is proposed. ‘Minimal’ data collection will assess the differential price of ‘healthy’ and ‘less healthy’ foods; ‘expanded’ monitoring will assess the differential price of ‘healthy’ and ‘less healthy’ diets; and the ‘optimal’ approach will also monitor food affordability, by taking into account household income. The monitoring of the price and affordability of ‘healthy’ and ‘less healthy’ foods and diets globally will provide robust data and benchmarks to inform economic and fiscal policy responses. Given the range of methodological, cultural and logistical challenges in this area, it is imperative that all aspects of the proposed monitoring framework are tested rigorously before implementation.

Monitoring foods and beverages provided and sold in public sector settings

This paper outlines a step-wise framework for monitoring foods and beverages provided or sold in publicly funded institutions. The focus is on foods in schools, but the framework can also be applied to foods provided or sold in other publicly funded institutions. Data collection and evaluation within this monitoring framework will consist of two components. In component I, information on existing food or nutrition policies and/or programmes within settings would be compiled. Currently, nutrition standards and voluntary guidelines associated with such policies/programmes vary widely globally. This paper, which provides a comprehensive review of such standards and guidelines, will facilitate institutional learnings for those jurisdictions that have not yet established them or are undergoing review of existing ones. In component II, the quality of foods provided or sold in public sector settings is evaluated relative to existing national or sub-national nutrition standards or voluntary guidelines. Where there are no (or only poor) standards or guidelines available, the nutritional quality of foods can be evaluated relative to standards of a similar jurisdiction or other appropriate standards. Measurement indicators are proposed (within ‘minimal’, ‘expanded’ and ‘optimal’ approaches) that can be used to monitor progress over time in meeting policy objectives, and facilitate comparisons between countries.

Hairpin RNAs derived from RNA polymerase II and polymerase III promoter-directed transgenes are processed differently in plants

RNA polymerase III (Pol III) as well as Pol II (35S) promoters are able to drive hairpin RNA (hpRNA) expression and induce target gene silencing in plants. siRNAs of 21 nt are the predominant species in a 35S Pol II line, whereas 24- and/or 22-nucleotide (nt) siRNAs are produced by a Pol III line. The 35S line accumulated the loop of the hpRNA, in contrast to full-length hpRNA in the Pol III line. These suggest that Pol II and Pol III-transcribed hpRNAs are processed by different pathways. One Pol III transgene produced only 24-nt siRNAs but silenced the target gene efficiently, indicating that the 24-nt siRNAs can direct mRNA degradation; specific cleavage was confirmed by 59 rapid amplification of cDNA ends (RACE). Both Pol II- and Pol III-directed hpRNA transgenes induced cytosine methylation in the target DNA. The extent of methylation is not correlated with the level of 21-nt siRNAs, suggesting that they are not effective inducers of DNA methylation. The promoter of a U6 transgene was significantly methylated, whereas the promoter of the endogenous U6 gene was almost free of cytosine methylation, suggesting that endogenous sequences are more resistant to de novo DNA methylation than are transgene constructs. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 RNA Society.