A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.

The DigiBog model of peatland development 1: rationale, conceptual model, and hydrological basis

Using a literature review, we argue that new models of peatland development are needed. Many existing models do not account for potentially important ecohydrological feedbacks, and/or ignore spatial structure and heterogeneity. Existing models, including those that simulate a near total loss of the northern peatland carbon store under a warming climate, may produce misleading results because they rely upon oversimplified representations of ecological and hydrological processes. In this, the first of a pair of papers, we present the conceptual framework for a model of peatland development, DigiBog, which considers peatlands as complex adaptive systems. DigiBog accounts for the interactions between the processes which govern litter production and peat decay, peat soil hydraulic properties, and peatland water-table behaviour, in a novel and genuinely ecohydrological manner. DigiBog consists of a number of interacting submodels, each representing a different aspect of peatland ecohydrology. Here we present in detail the mathematical and computational basis, as well as the implementation and testing, of the hydrological submodel. Remaining submodels are described and analysed in the accompanying paper. Tests of the hydrological submodel against analytical solutions for simple aquifers were highly successful: the greatest deviation between DigiBog and the analytical solutions was 2·83%. We also applied the hydrological submodel to irregularly shaped aquifers with heterogeneous hydraulic properties—situations for which no analytical solutions exist—and found the model's outputs to be plausible.

Reconciling model and information uncertainty in development appraisal

This paper investigates the effect of choices of model structure and scale in development viability appraisal. The paper addresses two questions concerning the application of development appraisal techniques to viability modelling within the UK planning system. The first relates to the extent to which, given intrinsic input uncertainty, the choice of model structure significantly affects model outputs. The second concerns the extent to which, given intrinsic input uncertainty, the level of model complexity significantly affects model outputs. Monte Carlo simulation procedures are applied to a hypothetical development scheme in order to measure the effects of model aggregation and structure on model output variance. It is concluded that, given the particular scheme modelled and unavoidably subjective assumptions of input variance, simple and simplistic models may produce similar outputs to more robust and disaggregated models.

The UK Department of National Heritage: a model for the development and integration of leisure policy in the new Europe?

Leisure is in the vanguard of a social and cultural revolution which is replacing the former East/West political bipolarity with a globalised economic system in which the new Europe has a central rôle. Within this revolution, leisure, including recreation, culture and tourism, is constructed as the epitome of successful capitalist development; the very legitimisation of the global transmogrification from a production to a consumption orientation. While acting as a direct encouragement to the political transformation in many eastern European states, it is uncertain how the issue of leisure policy is being handled, given its centrality to the new economic order. This paper therefore examines the experience of western Europe, considering in particular the degree to which the newly-created Department of National Heritage in the UK provides a potential model for leisure development and policy integration in the new Europe. Despite an official rhetoric of support and promotion of leisure activities, reflecting the growing economic significance of tourism and the positive relationship between leisure provision and regional economic development, the paper establishes that in the place of the traditional rôle of the state in promoting leisure interests, the introduction of the Department has signified a shift to the use of leisure to promote the Government's interests, particularly in regenerating citizen rights claims towards the market. While an institution such as the Department of National Heritage may have relevance to emerging states as a element in the maintenance of political hegemony, therefore, it is questionable how far it can be viewed as a promoter or protector of leisure as a signifier of a newly-won political, economic and cultural freedom throughout Europe.

Development of an ex vivo human skin model for intradermal vaccination : tissue viability and Langerhans cell behaviour

The presence of resident Langerhans cells (LCs) in the epidermis makes the skin an attractive target for DNA vaccination. However, reliable animal models for cutaneous vaccination studies are limited. We demonstrate an ex vivo human skin model for cutaneous DNA vaccination which can potentially bridge the gap between pre-clinical in vivo animal models and clinical studies. Cutaneous transgene expression was utilised to demonstrate epidermal tissue viability in culture. LC response to the culture environment was monitored by immunohistochemistry. Full-thickness and split-thickness skin remained genetically viable in culture for at least 72 h in both phosphate-buffered saline (PBS) and full organ culture medium (OCM). The epidermis of explants cultured in OCM remained morphologically intact throughout the culture duration. LCs in full-thickness skin exhibited a delayed response (reduction in cell number and increase in cell size) to the culture conditions compared with split-thickness skin, whose response was immediate. In conclusion, excised human skin can be cultured for a minimum of 72 h for analysis of gene expression and immune cell activation. However, the use of split-thickness skin for vaccine formulation studies may not be appropriate because of the nature of the activation. Full-thickness skin explants are a more suitable model to assess cutaneous vaccination ex vivo.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Development of a wind gust model to estimate gust speeds and their return periods

Spatially dense observations of gust speeds are necessary for various applications, but their availability is limited in space and time. This work presents an approach to help to overcome this problem. The main objective is the generation of synthetic wind gust velocities. With this aim, theoretical wind and gust distributions are estimated from 10 yr of hourly observations collected at 123 synoptic weather stations provided by the German Weather Service. As pre-processing, an exposure correction is applied on measurements of the mean wind velocity to reduce the influence of local urban and topographic effects. The wind gust model is built as a transfer function between distribution parameters of wind and gust velocities. The aim of this procedure is to estimate the parameters of gusts at stations where only wind speed data is available. These parameters can be used to generate synthetic gusts, which can improve the accuracy of return periods at test sites with a lack of observations. The second objective is to determine return periods much longer than the nominal length of the original time series by considering extreme value statistics. Estimates for both local maximum return periods and average return periods for single historical events are provided. The comparison of maximum and average return periods shows that even storms with short average return periods may lead to local wind gusts with return periods of several decades. Despite uncertainties caused by the short length of the observational records, the method leads to consistent results, enabling a wide range of possible applications.

The persistence of distance: a gravity model of European cross-border real estate development flows

Purpose – This paper aims to investigate the scale and drivers of cross-border real estate development in Western Europe and Central and Eastern Europe. Design/methodology/approach – Placing cross-border real estate development within the framework of foreign direct investment (FDI), conceptual complexities in characterizing the notional real estate developer are emphasized. Drawing upon a transaction database, this paper proxies cross-border real estate development flows with asset sales by developers. Findings – Much higher levels of market penetration by international real estate developers are found in the less mature markets of Central and Eastern Europe. Analysis suggests a complex range of determinants with physical distance remaining a consistent barrier to cross-border development flows. Originality/value – This analysis adds significant value in terms of understanding cross-border real estate development flows. In this study, a detailed examination of the issues based on a rigorous empirical analysis through gravity modelling is offered. The gravity framework is one of the most confirmed empirical regularities in international economics and commonly applied to trade, FDI, migration, foreign portfolio investment inter alia. This paper assesses the extent to which it provides useful insights into the pattern of cross-border real estate development flows.

A modified rat model of neonatal anoxia: Development and evaluation by pulseoximetry, arterial gasometry and Fos immunoreactivity

Neonatal anoxia is a worldwide clinical problem that has serious and lasting consequences. The diversity of models does not allow complete reproducibility, so a standardized model is needed. In this study, we developed a rat model of neonatal anoxia that utilizes a semi-hermetic system suitable for oxygen deprivation. The validity of this model was confirmed using pulse oximetry, arterial gasometry, observation of skin color and behavior and analysis of Fos immunoreactivity in brain regions that function in respiratory control. For these experiments, 87 male albino neonate rats (Rattus norvegicus, lineage Wistar) aged approximate 30 postnatal hours were divided into anoxia and control groups. The pups were kept in an euthanasia polycarbonate chamber at 36 +/- 1 degrees C, with continuous 100% nitrogen gas flow at 3 L/min and 101.7 kPa for 25 min. The peripheral arterial oxygen saturation of the anoxia group decreased 75% from its initial value. Decreased pH and partial pressure of oxygen and increased partial pressure of carbon dioxide were observed in this group, indicating metabolic acidosis, hypoxia and hypercapnia. respectively. Analysis of neuronal activation showed Fos immunoreactivity in the solitary tract nucleus, the lateral reticular nucleus and the area postrema, confirming that those conditions activated areas related to respiratory control in the nervous system. Therefore, the proposed model of neonatal anoxia allows standardization and precise control of the anoxic condition, which should be of great value in indentifying both the mechanisms underlying neonatal anoxia and novel therapeutic strategies to combat or prevent this widespread public health problem. (C) 2011 Elsevier B.V. All rights reserved.

Development and evaluation of a range anxiety-reducing business model for connected full electric vehicles

This thesis develops and evaluates a business model for connected full electric vehicles (FEV) for the European market. Despite a promoting political environment, various barriers have thus far prevented the FEV from becoming a mass-market vehicle. Besides cost, the most noteworthy of these barriers is represented by range anxiety, a product of FEVs’ limited range, lacking availability of charging infrastructure, and long recharging times. Connected FEVs, which maintain a constant connection to the surrounding infrastructure, appear to be a promising element to overcome drivers’ range anxiety. Yet their successful application requires a well functioning FEV ecosystem which can only be created through the collaboration of various stakeholders such as original equipment manufacturers (OEM), first tier suppliers (FTS), charging infrastructure and service providers (CISP), utilities, communication enablers, and governments. This thesis explores and evaluates how a business model, jointly created by these stakeholders, could look like, i.e. how stakeholders could collaborate in the design of products, services, infrastructure, and advanced mobility management, to meet drivers with a sensible value proposition that is at least equivalent to that of internal combustion engine (ICE) cars. It suggests that this value proposition will be an end-2-end package provided by CISPs or OEMs that comprises mobility packages (incl. pay per mile plans, battery leasing, charging and battery swapping (BS) infrastructure) and FEVs equipped with an on-board unit (OBU) combined with additional services targeted at range anxiety reduction. From a theoretical point of view the thesis answers the question which business model framework is suitable for the development of a holistic, i.e. all stakeholder-comprising business model for connected FEVs and defines such a business model. In doing so the thesis provides the first comprehensive business model related research findings on connected FEVs, as prior works focused on the much less complex scenario featuring only “offline” FEVs.