Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases

Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.

New-consensus macroeconomic governance in a Keynesian world, and the Keynesian alternative

The paper presents both the New Consensus and Keynesian equilibrium within the usual four competitive macro-markets structure. It gives theoretical explanations of the pernicious effects that the NCM governance, which has been designed for ergodic stationary regimes, brings about in Keynesian non-ergodic regimes. It put forward Keynesian principles of governance which include monetary, budgetary and fiscal instruments, and suggest new directions for the positive and normative analysis of macro-policies.

An account of new developmentalism and its structuralist macroeconomics

This is a personal account of the definition of "new developmentalism" - a national development strategy alternative to the Washington consensus -, and of a "structuralist development macroeconomics": the sum of models that justifies theoretically that strategy. It is personal account of a collective work involving Keynesian, institutionalist and structuralist economists in Brazil that are forming a new school of thought in Brazil: a Keynesian-structuralist school. It is Keynesian because it emphasizes the demand side or the investment opportunities' side of economic growth. It is institutionalist because institutions obviously matter in achieving growth and stability. It is structuralist because it defines economic development as a structural change from low to high value added per capita industries and because it is based on two structural tendencies that limit investment opportunities: the tendency of wages to grow below productivity and the tendency to the cyclical overvaluation of the exchange rate.

Logit models for identifying the factors that influence the uptake of new 'no-tillage' technologies by farmers in the rice-wheat and the cotton-wheat farming systems of Pakistan's Punjab

In the 'rice-wheat' and the 'cotton-wheat' farming systems of Pakistan's Punjab, late planting of wheat is a perennial problem due to often delayed harvesting of the previously planted and late maturing rice and cotton crops. This leaves very limited time for land preparation for 'on-time' planting of wheat. 'No-tillage' technologies that reduce the turn-round time for wheat cultivation after rice and cotton have been developed, but their uptake has not been as expected.-This paper attempts to determine the farm and farmer characteristics and other socio-economic factors that influence the adoption of 'no-tillage' technologies'. Logit models were developed for the analysis undertaken. In the 'cotton-wheat' system personal characteristics like education, tenancy status, attitude towards risk implied in the use of new technologies and contact with extension agents are the main factors that affect adoption. As regards the 'rice-wheat' system, resource endowments such as farm size, access to a 'no-tillage' drill, clayey soils and the area sown to the rice-wheat sequence along with tenancy and contact with extension agents were dominant in explaining adoption. (C) 2002 Elsevier Science Ltd. All rights reserved.

Hyper-parallel tempering Monte Carlo simulations of Ar adsorption in new models of microporous non-graphitizing activated carbon: effect of microporosity

The adsorption of gases on microporous carbons is still poorly understood, partly because the structure of these carbons is not well known. Here, a model of microporous carbons based on fullerene- like fragments is used as the basis for a theoretical study of Ar adsorption on carbon. First, a simulation box was constructed, containing a plausible arrangement of carbon fragments. Next, using a new Monte Carlo simulation algorithm, two types of carbon fragments were gradually placed into the initial structure to increase its microporosity. Thirty six different microporous carbon structures were generated in this way. Using the method proposed recently by Bhattacharya and Gubbins ( BG), the micropore size distributions of the obtained carbon models and the average micropore diameters were calculated. For ten chosen structures, Ar adsorption isotherms ( 87 K) were simulated via the hyper- parallel tempering Monte Carlo simulation method. The isotherms obtained in this way were described by widely applied methods of microporous carbon characterisation, i. e. Nguyen and Do, Horvath - Kawazoe, high- resolution alpha(a)s plots, adsorption potential distributions and the Dubinin - Astakhov ( DA) equation. From simulated isotherms described by the DA equation, the average micropore diameters were calculated using empirical relationships proposed by different authors and they were compared with those from the BG method.

An overview of domestic energy models and a new approach with agent based modelling

Government targets for CO2 reductions are being progressively tightened, the Climate Change Act set the UK target as an 80% reduction by 2050 on 1990 figures. The residential sector accounts for about 30% of emissions. This paper discusses current modelling techniques in the residential sector: principally top-down and bottom-up. Top-down models work on a macro-economic basis and can be used to consider large scale economic changes; bottom-up models are detail rich to model technological changes. Bottom-up models demonstrate what is technically possible. However, there are differences between the technical potential and what is likely given the limited economic rationality of the typical householder. This paper recommends research to better understand individuals’ behaviour. Such research needs to include actual choices, stated preferences and opinion research to allow a detailed understanding of the individual end user. This increased understanding can then be used in an agent based model (ABM). In an ABM, agents are used to model real world actors and can be given a rule set intended to emulate the actions and behaviours of real people. This can help in understanding how new technologies diffuse. In this way a degree of micro-economic realism can be added to domestic carbon modelling. Such a model should then be of use for both forward projections of CO2 and to analyse the cost effectiveness of various policy measures.

Root growth models: towards a new generation of continuous approaches

Models of root system growth emerged in the early 1970s, and were based on mathematical representations of root length distribution in soil. The last decade has seen the development of more complex architectural models and the use of computer-intensive approaches to study developmental and environmental processes in greater detail. There is a pressing need for predictive technologies that can integrate root system knowledge, scaling from molecular to ensembles of plants. This paper makes the case for more widespread use of simpler models of root systems based on continuous descriptions of their structure. A new theoretical framework is presented that describes the dynamics of root density distributions as a function of individual root developmental parameters such as rates of lateral root initiation, elongation, mortality, and gravitropsm. The simulations resulting from such equations can be performed most efficiently in discretized domains that deform as a result of growth, and that can be used to model the growth of many interacting root systems. The modelling principles described help to bridge the gap between continuum and architectural approaches, and enhance our understanding of the spatial development of root systems. Our simulations suggest that root systems develop in travelling wave patterns of meristems, revealing order in otherwise spatially complex and heterogeneous systems. Such knowledge should assist physiologists and geneticists to appreciate how meristem dynamics contribute to the pattern of growth and functioning of root systems in the field.

Taking the shopping centre online: new models in e-commerce

Purpose – This paper aims to provide a brief re´sume´ of previous research which has analysed the impact of e-commerce on retail real estate in the UK, and to examine the important marketing role of the internet for shopping centre managers, and retail landlords. Design/methodology/approach – Based on the results from a wider study carried out in 2003, the paper uses case studies from two different shopping centres in the UK, and documents the innovative uses of both web-based marketing and online retailing by organisations that historically have not directly been involved in the retailing process. Findings – The paper highlights the importance of considering online sales within a multi-channel approach to retailing. The two types of emerging shopping centre model which are identified are characterised by their ultimate relationship with the physical shopping centre on whose web site they reside. These can be summarised as: the “centre-led” approach, and the “brand-led” or “marketing-led” approach. Research limitations/implications – The research is based on a limited number of in-depth case studies and secondary data. Further research is needed to monitor the continuing impact of e-commerce on retail property and the marketing strategies of shopping centre managers and owners. Practical implications – Internet-based sales provide an important adjunct to conventional retail sales and an important source of potential risk for landlords and tenants in the real estate investment market. Regardless of whether retailers use the internet as a sales channel, as a product-sourcing tool, or merely to provide information to the consumer, the internet has become a keystone within the greater retail marketing mix. The findings have ramifications for understanding the way in which landlords are structuring their retail property to defray potential risks. Originality/value – The paper examines shopping centre online marketing models for the first time in detail, and will be of value to retail occupiers, owners and other stakeholders of shopping centres.

New models of North West European Holocene palaeogeography and inundation

This paper presents new 500 year interval palaeogeographic models for Britain, Ireland and the North West French coast from 11000 cal. BP to present. These models are used to calculate the varying rates of inundation for different geographical zones over the study period. This allows for consideration of the differential impact that Holocene sea-level rise had across space and time, and on past societies. In turn, consideration of the limitations of the models helps to foreground profitable areas for future research.

A new class of survival regression models with heavy-tailed errors: robustness and diagnostics

Birnbaum-Saunders models have largely been applied in material fatigue studies and reliability analyses to relate the total time until failure with some type of cumulative damage. In many problems related to the medical field, such as chronic cardiac diseases and different types of cancer, a cumulative damage caused by several risk factors might cause some degradation that leads to a fatigue process. In these cases, BS models can be suitable for describing the propagation lifetime. However, since the cumulative damage is assumed to be normally distributed in the BS distribution, the parameter estimates from this model can be sensitive to outlying observations. In order to attenuate this influence, we present in this paper BS models, in which a Student-t distribution is assumed to explain the cumulative damage. In particular, we show that the maximum likelihood estimates of the Student-t log-BS models attribute smaller weights to outlying observations, which produce robust parameter estimates. Also, some inferential results are presented. In addition, based on local influence and deviance component and martingale-type residuals, a diagnostics analysis is derived. Finally, a motivating example from the medical field is analyzed using log-BS regression models. Since the parameter estimates appear to be very sensitive to outlying and influential observations, the Student-t log-BS regression model should attenuate such influences. The model checking methodologies developed in this paper are used to compare the fitted models.

Some restriction tests in a new class of regression models for proportions

The main purpose of this work is to study the behaviour of Skovgaard`s [Skovgaard, I.M., 2001. Likelihood asymptotics. Scandinavian journal of Statistics 28, 3-32] adjusted likelihood ratio statistic in testing simple hypothesis in a new class of regression models proposed here. The proposed class of regression models considers Dirichlet distributed observations, and the parameters that index the Dirichlet distributions are related to covariates and unknown regression coefficients. This class is useful for modelling data consisting of multivariate positive observations summing to one and generalizes the beta regression model described in Vasconcellos and Cribari-Neto [Vasconcellos, K.L.P., Cribari-Neto, F., 2005. Improved maximum likelihood estimation in a new class of beta regression models. Brazilian journal of Probability and Statistics 19,13-31]. We show that, for our model, Skovgaard`s adjusted likelihood ratio statistics have a simple compact form that can be easily implemented in standard statistical software. The adjusted statistic is approximately chi-squared distributed with a high degree of accuracy. Some numerical simulations show that the modified test is more reliable in finite samples than the usual likelihood ratio procedure. An empirical application is also presented and discussed. (C) 2009 Elsevier B.V. All rights reserved.

New models of old(?) payment questions

Is private money feasible and desirable? In its absence, is there a central bank policy that partially or fully substitutes for private money? In this paper, some recent modeling ideas about how to address these questioned are reviewed and applied. The main ideas are that people cannot commit to future actions and that their histories are to some extent unknown - are not common knowledge. Under the additional assumption that the private monies issued by diferent people are distinct, a strong recognizability assumption, it is shown that there is a role for private money.

New class of spin projection operators for 3D models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)