USTOPIA REQUIREMENTS THOUGHTS ON A USER-FRIENDLY SYSTEM FOR TRANSFORMATION OF PROGRAMS IN ABSTRACTO

Transformational programming is a program development method which is usually applied using 'pen and paper'. Since this requires a lot of clerical work (copying expressions, con- sistent substitution) which is tiresome and prone to error, some form of machine support is desirable. In this paper a number of systems are described that have already been built to this aim. Some of their shortcomings and limitations are identified. Based on experience with program transformation and transformation systems, a long list of features is given that would be useful in an 'utopian' transformation system. This list is presented using an orthogonal division of the problem area. A number of problems with the realisation of some aspects of our 'utopian' system are identified, and some areas for further research are indicated

Examination of the effects of a new compression garment on skin tissue oxygenation in healthy volunteers

Objective: Compression devices have been shown to reduce venous stasis, increase blood flow and skin tissue oxygenation (StO2), promoting healthy tissue. This study aimed to explore the efficacy of a new compression garment in three different positions in healthy adults. Methods: In this quantitative study, potential participants were screened and recruited using the Physical Activity Readiness Questionnaire (PAR-Q, Canada). Participants attended three separate, one-hour sessions to evaluate StO2 in supine-lying, chair-sitting and long-sitting positions. StO2 was recorded for 20 minutes pre-, during and post- a 20-minute intervention using a compression garment, TributeWrap (Lohmann-Rauscher, Germany). A repeated-measures analysis of variance (ANOVA) was followed by post-hoc pairwise comparisons. Results: A total of 28 healthy volunteers took part (aged 24.6 ±8.4years; 13 males, 15 females). A significant difference was seen between the three positions (p<0.001). Chair-sitting had the lowest StO2 pre-intervention, increasing StO2 significantly (32.25%, p<0.001) during wear of the compression garment (24.8% higher than baseline post-intervention). No significant difference was seen between long sitting and supine-lying (p=1.000). In contrast, long-sitting and supine-lying StO2 was higher pre-intervention compared with chair-sitting and only increased post-intervention (11% and 16.8% respectively, p<0.001) compared with baseline. Conclusion: The compression garment significantly increased StO2 levels in both seating positions. Further studies are required to determine if increasing StO2 through short intervention sessions with this device has the potential to improve self-management of tissue health in individuals with reduced mobility, oedema or venous insufficiency

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Inconsistent impacts of decomposer diversity on the stability of aboveground and belowground ecosystem functions

The intensive discussion on the importance of biodiversity for the stability of essential processes in ecosystems has prompted a multitude of studies since the middle of the last century. Nevertheless, research has been extremely biased by focusing on the producer level, while studies on the impacts of decomposer diversity on the stability of ecosystem functions are lacking. Here, we investigate the impacts of decomposer diversity on the stability (reliability) of three important aboveground and belowground ecosystem functions: primary productivity (shoot and root biomass), litter decomposition, and herbivore infestation. For this, we analyzed the results of three laboratory experiments manipulating decomposer diversity (1–3 species) in comparison to decomposer-free treatments in terms of variability of the measured variables. Decomposer diversity often significantly but inconsistently affected the stability of all aboveground and belowground ecosystem functions investigated in the present study. While primary productivity was mainly destabilized, litter decomposition and aphid infestation were essentially stabilized by increasing decomposer diversity. However, impacts of decomposer diversity varied between plant community and fertility treatments. There was no general effect of the presence of decomposers on stability and no trend toward weaker effects in fertilized communities and legume communities. This indicates that impacts of decomposers are based on more than effects on nutrient availability. Although inconsistent impacts complicate the estimation of consequences of belowground diversity loss, underpinning mechanisms of the observed patterns are discussed. Impacts of decomposer diversity on the stability of essential ecosystem functions differed between plant communities of varying composition and fertility, implicating that human-induced changes of biodiversity and land-use management might have unpredictable effects on the processes mankind relies on. This study therefore points to the necessity of also considering soil feedback mechanisms in order to gain a comprehensive and holistic understanding of the impacts of current global change phenomena on the stability of essential ecosystem functions

Plant Diversity Surpasses Plant Functional Groups and Plant Productivity as Driver of Soil Biota in the Long Term

One of the most significant consequences of contemporary global change is the rapid decline of biodiversity in many ecosystems. Knowledge of the consequences of biodiversity loss in terrestrial ecosystems is largely restricted to single ecosystem functions. Impacts of key plant functional groups on soil biota are considered to be more important than those of plant diversity; however, current knowledge mainly relies on short-term experiments.We studied changes in the impacts of plant diversity and presence of key functional groups on soil biota by investigating the performance of soil microorganisms and soil fauna two, four and six years after the establishment of model grasslands. The results indicate that temporal changes of plant community effects depend on the trophic affiliation of soil animals: plant diversity effects on decomposers only occurred after six years, changed little in herbivores, but occurred in predators after two years. The results suggest that plant diversity, in terms of species and functional group richness, is the most important plant community property affecting soil biota, exceeding the relevance of plant above- and belowground productivity and the presence of key plant functional groups, i.e. grasses and legumes, with the relevance of the latter decreasing in time.Plant diversity effects on biota are not only due to the presence of key plant functional groups or plant productivity highlighting the importance of diverse and high-quality plant derived resources, and supporting the validity of the singular hypothesis for soil biota. Our results demonstrate that in the long term plant diversity essentially drives the performance of soil biota questioning the paradigm that belowground communities are not affected by plant diversity and reinforcing the importance of biodiversity for ecosystem functioning

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining1, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes4 across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.

Network meta-analysis of (individual patient) time to event data alongside (aggregate) count data

Objectives: Network meta-analysis (NMA) methods extend the standard pair-wise framework to allow simultaneous comparison of multiple interventions in a single statistical model. Despite published work on NMA mainly focussing on the synthesis of aggregate data (AD), methods have been developed that allow the use of individual patient-level data (IPD) specifically when outcomes are dichotomous or continuous. This paper focuses on the synthesis of IPD and AD time to event data, motivated by a real data example looking at the effectiveness of high compression treatments on the healing of venous leg ulcers. Methods: This paper introduces a novel NMA modelling approach that allows IPD (time to event with censoring) and AD (event count for a given follow-up time) to be synthesised jointly by assuming an underlying, common, distribution of time to healing. Alternative model assumptions were tested within the motivating example. Model fit and adequacy measures were used to compare and select models. Results: Due to the availability of IPD in our example we were able to use a Weibull distribution to describe time to healing; otherwise, we would have been limited to specifying a uniparametric distribution. Absolute effectiveness estimates were more sensitive than relative effectiveness estimates to a range of alternative specifications for the model. Conclusions: The synthesis of time to event data considering IPD provides modelling flexibility, and can be particularly important when absolute effectiveness estimates, and not just relative effect estimates, are of interest