Network Structure and Dynamics, and Emergence of Robustness by Stabilizing Selection in an Artificial Genome

Genetic regulation is a key component in development, but a clear understanding of the structure and dynamics of genetic networks is not yet at hand. In this work we investigate these properties within an artificial genome model originally introduced by Reil. We analyze statistical properties of randomly generated genomes both on the sequence- and network level, and show that this model correctly predicts the frequency of genes in genomes as found in experimental data. Using an evolutionary algorithm based on stabilizing selection for a phenotype, we show that robustness against single base mutations, as well as against random changes in initial network states that mimic stochastic fluctuations in environmental conditions, can emerge in parallel. Evolved genomes exhibit characteristic patterns on both sequence and network level.Comment: 7 pages, 7 figures. Submitted to the "8th German Workshop on Artificial Life (GWAL 8)

Imaging the Gamma-Ray Sky with SPI aboard INTEGRAL

The spectrometer SPI on INTEGRAL allows for the first time simultaneous imaging of diffuse and point-like emission in the hard X-ray and soft gamma-ray regime. To fully exploit the capabilities of the instrument, we implemented the MREM image deconvolution algorithm, initially developed for COMPTEL data analysis, to SPI data analysis. We present the performances of the algorithm by means of simulations and apply it to data accumulated during the first 2 mission years of INTEGRAL. Skymaps are presented for the 1809 keV gamma-ray line, attributed to the radioactive decay of 26Al, and for continuum energy bands, covering the range 20 keV - 3 MeV. The 1809 keV map indicates that emission is clearly detected by SPI from the inner Galactic radian and from the Cygnus region. The continuum maps reveal the transition between a point-source dominated hard X-ray sky to a diffuse emission dominated soft gamma-ray sky. From the skymaps, we extract a Galactic ridge emission spectrum that matches well SPI results obtained by model fitting. By comparing our spectrum with the cumulative flux measured by IBIS from point sources, we find indications for the existence of an unresolved or diffuse emission component above ~100 keV.Comment: 12 pages, 7 figure

False Discovery Rate and Localizing Power

False discovery rate (FDR) is commonly used for correction for multiple testing in neuroimaging studies. However, when using two-tailed tests, making directional inferences about the results can lead to vastly inflated error rate, even approaching 100% in some cases. This happens because FDR only provides weak control over the error rate, meaning that the proportion of error is guaranteed only globally over all tests, not within subsets, such as among those in only one or another direction. Here we consider and evaluate different strategies for FDR control with two-tailed tests, using both synthetic and real imaging data. Approaches that separate the tests by direction of the hypothesis test, or by the direction of the resulting test statistic, more properly control the directional error rate and preserve FDR benefits, albeit with a doubled risk of errors under complete absence of signal. Strategies that combine tests in both directions, or that use simple two-tailed p-values, can lead to invalid directional conclusions, even if these tests remain globally valid. To enable valid thresholding for directional inference, we suggest that imaging software should allow the possibility that the user sets asymmetrical thresholds for the two sides of the statistical map. While FDR continues to be a valid, powerful procedure for multiple testing correction, care is needed when making directional inferences for two-tailed tests, or more broadly, when making any localized inference

Planning for better animal health and welfare, Report from the 1st ANIPLAN project workshop, Hellevad, October 2007

’Minimising medicine use in organic dairy herds through animal health and welfare planning’, ANIPLAN, is a CORE-Organic project which was initiated in June 2007. The main aim of the project is to investigate active and well planned animal health and welfare promotion and disease prevention as a means of minimising medicine use in organic dairy herds. This aim will be met through the development of animal health and welfare planning principles for organic dairy farms under diverse conditions based on an evaluation of current experiences. This also includes application of animal health and welfare assessment across Europe. In order to bring this into practice the project also aims at developing guidelines for communication about animal health and welfare promotion in different settings, for example, as part of existing animal health advisory services or farmer groups such as the Danish Stable School system and the Dutch network programme. The project is divided into the following five work packages, four of which comprise research activities with the other focused on coordination and knowledge transfer, through meetings, workshops and publications. These proceedings represent our first results in terms of presented papers and discussions at our first project workshop in Hellevad Vandmølle as well as a review of Animal Health Planning in UK. The content of the workshop proceedings reflect the aim and starting points of all work packages, both in terms of analyses prior to the workshop, and developments during the workshop emanating from group work. Besides a general introduction to the project and the ideas of the project, Christoph Winckler provides an overview of the use of animal based parameters based on the results of the WelfareQuality project. Christopher Atkinson and Madeleine Neale presented concepts, principles and the practicalities of Animal Health Planning and Animal Health Plans based on UK experiences. Pip Nicholas from The University of Wales, Aberystwyth produced a report reviewing the current use of animal health and welfare planning. The entire document is included in these workshop proceedings. This was supplemented through presentations from all countries regarding animal health and welfare planning processes and research. These are summarised together with the concepts developed through dialogue at the workshop in the paper by Nicholas, Vaarst and Roderick. Finally, the Danish Stable School principles were presented by Mette Vaarst followed by discussion on different approaches of communication in farmer groups and at the individual level between farmers and advisors. One important outcome from this workshop is a set of preliminary principles for a good health planning process. We concluded through group discussions followed by a plenary session that a health planning process should aim at continuous development and improvement, and should incorporate health promotion and disease handling, based on a strategy where the current situation is evaluated and form basis for action, which is then reviewed in a new evaluation. It is important that any health plan is farm specific and based on farmer ownership, although an external person(s) should be involved, as well as external knowledge. The organic principles should form the framework for any action (meaning that a systems approach is needed), and the plan should be written. The good and positive aspects on each farm – things that other farmers potentially can learn from. The work and studies in dairy farms within the project will be based on these principles and comprise evaluation and review using animal based parameters as well as finding ways of communication with farmers about animal health and welfare

Transnational engagements: cultural and religious practices related to menstruation

This transnational engagement brings together participants from various cultural and religious backgrounds in a dialogue about menstrual practices. They are asked to consider their own experiences with these practices and reflect on how the practices have affected them. The discussion makes clear that participants have varying understandings and views of traditional menstrual practices, and that these views often challenge the common depiction of traditional practices as restrictions that are forced upon women

Adapting Behavioral Parent Training as an Interactive Computer Game

Behavioral Parent Training (BPT) is a well-established therapy that reduces child externalized behaviors and parent stress. Although BPT was originally developed for parents of children with defiant behaviors, the program’s key concepts are relevant to parenting all children. Since parents might not fully utilize BPT due to cost and program location, we created an online game as a low-cost, easily accessible alternative or complement to BPT. We tested the game with nineteen undergraduate students at the University of Maryland. The experimental group completed pretest survey on core BPT knowledge, played the game, and completed a BPT posttest, while the control group completed a pretest and posttest survey over a three week period. Participants in the experimental group also completed a survey to indicate their satisfaction with the overall program. The experimental group demonstrated significantly higher levels of BPT knowledge than the control group and high levels of satisfaction. This suggests that an interactive, online BPT platform is an engaging and accessible way for parents to learn key concepts

Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA

Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Le(b) antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Le(b) at 2.0- and 2.1-Å resolutions, respectively. BabA is a predominantly α-helical molecule with a markedly kinked tertiary structure containing a single, shallow Le(b) binding site at its tip within a β-strand motif. No conformational change occurs in BabA upon binding of Le(b), which is characterized by low affinity under acidic [K D (dissociation constant) of ~227 μM] and neutral (K D of ~252 μM) conditions. Binding is mediated by a network of hydrogen bonds between Le(b) Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Le(b), respectively. Knowledge of the molecular basis of Le(b) recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa

One-year changes in brain microstructure differentiate preclinical Huntington's disease stages.

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period. RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the corpus callosum. This overall effect was driven by significant differences between the group far-from-onset (FAR) of symptoms and the groups midway- (MID) and near-the-onset (NEAR) of symptoms. In particular, an initial decrease of mean diffusivity in the FAR group was followed by a subsequent increase in groups closer to onset of symptoms. The seemingly counter-intuitive decrease of mean diffusivity in the group furthest from onset of symptoms might be an early indicator of neuroinflammatory process preceding the neurodegenerative phase. In contrast, the only clinical measure that was able to capture a difference in 1y changes between the preclinical stages was the UHDRS confidence in motor score. CONCLUSIONS: With sensitivity to longitudinal changes in brain microstructure within and between preclinical stages, and potential differential response to distinct pathophysiological mechanisms, diffusion imaging is a promising state marker for monitoring treatment response and identifying the optimal therapeutic window of opportunity in preclinical Huntington's disease

Electric field tunable superconductor-semiconductor coupling in Majorana nanowires

We study the effect of external electric fields on superconductor-semiconductor coupling by measuring the electron transport in InSb semiconductor nanowires coupled to an epitaxially grown Al superconductor. We find that the gate voltage induced electric fields can greatly modify the coupling strength, which has consequences for the proximity induced superconducting gap, effective g-factor, and spin-orbit coupling, which all play a key role in understanding Majorana physics. We further show that level repulsion due to spin-orbit coupling in a finite size system can lead to seemingly stable zero bias conductance peaks, which mimic the behavior of Majorana zero modes. Our results improve the understanding of realistic Majorana nanowire systems.Comment: 10 pages, 5 figures, supplemental information as ancillary fil

Materials for stem cell factories of the future

The materials community is now identifying polymeric substrates that could permit translation of human pluripotent stem cells (hPSCs) from lab-based research to industrial scale biomedicine. Well defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large scale drug screening programs and clinical use, wherein >1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells for one patient is challenging and a rethink is needed to scalable technology with the potential to meet the needs of millions of patients a year. Here we consider the role of materials discovery, an emerging area of materials chemistry that is in a large part driven by the challenges posed by biologists to materials scientists1-4