A metabolic system-wide characterisation of the pig: a model for human physiology

The pig is a single-stomached omnivorous mammal and is an important model of human disease and nutrition. As such, it is necessary to establish a metabolic framework from which pathology-based variation can be compared. Here, a combination of one and two-dimensional 1H and 13C nuclear magnetic resonance spectroscopy (NMR) and high-resolution magic angle spinning (HR-MAS) NMR was used to provide a systems overview of porcine metabolism via characterisation of the urine, serum, liver and kidney metabolomes. The metabolites observed in each of these biological compartments were found to be qualitatively comparable to the metabolic signature of the same biological matrices in humans and rodents. The data were modelled using a combination of principal components analysis and Venn diagram mapping. Urine represented the most metabolically distinct biological compartment studied, with a relatively greater number of NMR detectable metabolites present, many of which are implicated in gut-microbial co-metabolic processes. The major interspecies differences observed were in the phase II conjugation of extra-genomic metabolites; the pig was observed to conjugate p-cresol, a gut microbial metabolite of tyrosine, with glucuronide rather than sulfate as seen in man. These observations are important to note when considering the translatability of experimental data derived from porcine models.

Modelling capability and affordance as properties of human/machine resource systems

Understanding how and why the capability of one set of business resources, its structural arrangements and mechanisms compared to another works can provide competitive advantage in terms of new business processes and product and service development. However, most business models of capability are descriptive and lack formal modelling language to qualitatively and quantifiably compare capabilities, Gibson’s theory of affordance, the potential for action, provides a formal basis for a more robust and quantitative model, but most formal affordance models are complex and abstract and lack support for real-world applications. We aim to understand the ‘how’ and ‘why’ of business capability, by developing a quantitative and qualitative model that underpins earlier work on Capability-Affordance Modelling – CAM. This paper integrates an affordance based capability model and the formalism of Coloured Petri Nets to develop a simulation model. Using the model, we show how capability depends on the space time path of interacting resources, the mechanism of transition and specific critical affordance factors relating to the values of the variables for resources, people and physical objects. We show how the model can identify the capabilities of resources to enable the capability to inject a drug and anaesthetise a patient.

Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats

Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

The greening of Arabia: multiple opportunities for human occupation of the Arabian peninsula during the Late Pleistocene inferred from an ensemble of climate model simulations

Climate models are potentially useful tools for addressing human dispersals and demographic change. The Arabian Peninsula is becoming increasingly significant in the story of human dispersals out of Africa during the Late Pleistocene. Although characterised largely by arid environments today, emerging climate records indicate that the peninsula was wetter many times in the past, suggesting that the region may have been inhabited considerably more than hitherto thought. Explaining the origins and spatial distribution of increased rainfall is challenging because palaeoenvironmental research in the region is in an early developmental stage. We address environmental oscillations by assembling and analysing an ensemble of five global climate models (CCSM3, COSMOS, HadCM3, KCM, and NorESM). We focus on precipitation, as the variable is key for the development of lakes, rivers and savannas. The climate models generated here were compared with published palaeoenvironmental data such as palaeolakes, speleothems and alluvial fan records as a means of validation. All five models showed, to varying degrees, that the Arabia Peninsula was significantly wetter than today during the Last Interglacial (130 ka and 126/125 ka timeslices), and that the main source of increased rainfall was from the North African summer monsoon rather than the Indian Ocean monsoon or from Mediterranean climate patterns. Where available, 104 ka (MIS 5c), 56 ka (early MIS 3) and 21 ka (LGM) timeslices showed rainfall was present but not as extensive as during the Last Interglacial. The results favour the hypothesis that humans potentially moved out of Africa and into Arabia on multiple occasions during pluvial phases of the Late Pleistocene.

1,8-cineol potentiates IRF3-mediated antiviral response in human stem cells and an ex vivo model of rhinosinusitis

Common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial super-infections resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential of 1,8-cineole for treating primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates Poly(I:C)-induced activity of the anti-viral transcription factor Interferon Regulatory Factor 3, while simultaneously reducing pro-inflammatory NF-κB-activity in human cell lines, inferior turbinate stem cells (ITSCs) and ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with Poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared to Poly(I:C) alone, whereas NF-κB-activity was reduced. Accordingly, 1,8-cineole- and Poly(I:C)-treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared to the Poly(I:C)-treated approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with LPS and 1,8-cineole compared to the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on pro-inflammatory NF-κB-signalling and may thus broaden its field of application.

Temporal lobe epilepsy and social behavior: An animal model

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology. (c) 2008 Elsevier Inc. All rights reserved.

CRITICAL BEHAVIOR AND THRESHOLD OF COEXISTENCE OF A PREDATOR-PREY STOCHASTIC MODEL IN A 2D LATTICE

We investigate the critical behavior of a stochastic lattice model describing a predator-prey system. By means of Monte Carlo procedure we simulate the model defined on a regular square lattice and determine the threshold of species coexistence, that is, the critical phase boundaries related to the transition between an active state, where both species coexist and an absorbing state where one of the species is extinct. A finite size scaling analysis is employed to determine the order parameter, order parameter fluctuations, correlation length and the critical exponents. Our numerical results for the critical exponents agree with those of the directed percolation universality class. We also check the validity of the hyperscaling relation and present the data collapse curves.

An analysis of quit and dismissal determinants between 1988 and 1999 using the bivariate probit model

Excessive labor turnover may be considered, to a great extent, an undesirable feature of a given economy. This follows from considerations such as underinvestment in human capital by firms. Understanding the determinants and the evolution of turnover in a particular labor market is therefore of paramount importance, including policy considerations. The present paper proposes an econometric analysis of turnover in the Brazilian labor market, based on a partial observability bivariate probit model. This model considers the interdependence of decisions taken by workers and firms, helping to elucidate the causes that lead each of them to end an employment relationship. The Employment and Unemployment Survey (PED) conducted by the State System of Data Analysis (SEADE) and by the Inter-Union Department of Statistics and Socioeconomic Studies (DIEESE) provides data at the individual worker level, allowing for the estimation of the joint probabilities of decisions to quit or stay on the job on the worker’s side, and to maintain or fire the employee on the firm’s side, during a given time period. The estimated parameters relate these estimated probabilities to the characteristics of workers, job contracts, and to the potential macroeconomic determinants in different time periods. The results confirm the theoretical prediction that the probability of termination of an employment relationship tends to be smaller as the worker acquires specific skills. The results also show that the establishment of a formal employment relationship reduces the probability of a quit decision by the worker, and also the firm’s firing decision in non-industrial sectors. With regard to the evolution of quit probability over time, the results show that an increase in the unemployment rate inhibits quitting, although this tends to wane as the unemployment rate rises.

Endogenous wage compression and aggregation boundaries in a model of hierarchical human capital

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Characterization and oxygen binding properties of des-Arg human hemoglobin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

On high Q(2) behavior of the pion form factor for transitions gamma*gamma -> pi(0) and gamma*gamma* -> pi(0) within the nonlocal quark-pion model

The behavior of the transition pion form factor for processes gamma (*)gamma --> pi(0) and gamma (*)gamma (*) --> pi(0) at large values of space-like photon momenta is estimated within the nonlocal covariant quark-pion model. It is shown that, in general, the coefficient of the leading asymptotic term depends dynamically on the ratio of the constituent quark mass and the average virtuality of quarks in the vacuum and kinematically on the ratio of photon virtualities. The kinematic dependence of the transition form factor allows us to obtain the relation between the pion light-cone distribution amplitude and the quark-pion vertex function. The dynamic dependence indicates that the transition form factor gamma (*)gamma -->, pi(0) at high momentum transfers is very sensitive to the nonlocality size of nonperturbative fluctuations in the QCD vacuum. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Dynamic critical behavior of percolation observables in the 2d Ising model

We present preliminary results of our numerical study of the critical dynamics of percolation observables for the two-dimensional Ising model. We consider the (Monte-Carlo) short-time evolution of the system obtained with a local heat-bath method and with the global Swendsen-Wang algorithm. In both cases, we find qualitatively different dynamic behaviors for the magnetization and Omega, the order parameter of the percolation transition. This may have implications for the recent attempts to describe the dynamics of the QCD phase transition using cluster observables.

Multistable behavior above synchronization in a locally coupled Kuramoto model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)