Phase transitions in gene networks evolved under different selection rules

Mathematical models of gene regulation are a powerful tool for understanding the complex features of genetic control. While various modeling efforts have been successful at explaining gene expression dynamics, much less is known about how evolution shapes the structure of these networks. An important feature of gene regulatory networks is their stability in response to environmental perturbations. Regulatory systems are thought to have evolved to exist near the transition between stability and instability, in order to have the required stability to environmental fluctuations while also being able to achieve a wide variety of functions (corresponding to different dynamical patterns). We study a simplified model of gene network evolution in which links are added via different selection rules. These growth models are inspired by recent work on `explosive' percolation which shows that when network links are added through competitive rather than random processes, the connectivity phase transition can be significantly delayed, and when it is reached, it appears to be first order (discontinuous, e.g., going from no failure at all to large expected failure) instead of second order (continuous, e.g., going from no failure at all to very small expected failure). We find that by modifying the traditional framework for networks grown via competitive link addition to capture how gene networks evolve to avoid damage propagation, we also see significant delays in the transition that depend on the selection rules, but the transitions always appear continuous rather than `explosive'.

Experimental and analytical study of cracks under biaxial fatigue

Most mechanical components experience multi-axial cyclic loading conditions during service. Experimental analysis of fatigue cracks under such conditions is not easy and most works tend to focus more on the simpler but less realistic case of uni-axial loading. Consequently, there are many uncertainties related to the load sequence effect that are now well known and are not normally incorporated into the growth models. The current work presents a new methodology for evaluating overload effect in biaxial fatigue cracks. The methodology includes evaluation of mixed-mode (KI and KII) stress intensity factor and the Crack Opening Displacement for samples with and without overload cycle under biaxial loading. The methodology is tested under a range of crack lengths. All crack-tip information is obtained with a hybrid methodology that combines experimental full-field digital image correlation data and Williams' elastic model describing the crack-tip field.

Life history of a wide-ranging deepwater lantern shark in the north-east Atlantic, Etmopterus spinax (Chondrichthyes: Etmopteridae), with implications for conservation

In this paper, the population biology of the velvet belly lanternshark Etmopterus spinax was studied and life-history coefficients determined. Age was estimated from sections of the second dorsal spine and validated by marginal increment analysis. Males attained a maximum age of 8 years while 11 year-old females were found. Several growth models were fitted and compared for both size-at-age and mass-at-age data, showing that even though this is a small-sized species, it has a relatively slow growth rate. This species matures late, specifically at 49.6 and 42.5% of the maximum observed ages for males and females, respectively. It has a low fecundity, with a mean ovarian fecundity of 9.94 oocytes and a mean uterine fecundity of 7.59 embryos per reproductive cycle. This species seems to have a long reproductive cycle, and even though no conclusive data were obtained, a 2-3 year cycle is possible. The estimated coefficients indicate that this species has a vulnerable life cycle, typical of deepwater squalid sharks. Given the high fishing pressures that it is suffering in the north-east Atlantic, this fish may already be facing severe declines or in risk of facing them in the near future. (C) 2008 The Authors Journal compilation (C) 2008 The Fisheries Society of the British Isles

Population parameters of the smooth lantern shark, Etmopterus pusillus, in southern Portugal (NE Atlantic)

Etmopterus pusillus is a deep water lantern shark with a widespread global distribution that is caught in large quantities in some areas, but is usually discarded due to the low commercial value. In this work, the population biology was studied and life history parameters determined for the first time in this species. Age was estimated from sections of the second dorsal spine and validated by marginal increment analysis. Males attained a maximum age of 13 years, while 17-year-old females were found. Several growth models were fitted and compared for both size and weight at age data, showing that even though this is a small sized species, it has a relatively slow growth rate. This species matures late and at a relatively large size: at 86.81% and 79.40% of the maximum observed sizes and at 58.02% and 54.40% of the maximum observed ages for males and females, respectively. It has a low fecundity, with a mean ovarian fecundity of 10.44 oocytes per reproductive cycle. The estimated parameters indicate that this species has a vulnerable life cycle, typical of deep water squalid sharks. Given the high fishing pressures that it is suffering in the NE Atlantic, the smooth lantern shark may be in danger of severe declines in the near future. (c) 2007 Elsevier B.V. All rights reserved.

El efecto de la definición regulatoria de banda ancha sobre la difusión y la competencia del mercado de servicios de Internet fijo en Colombia

A partir de la dinámica evolutiva de la economía de las Tecnologías de la Información y las Comunicaciones y el establecimiento de estándares mínimos de velocidad en distintos contextos regulatorios a nivel mundial, en particular en Colombia, en el presente artículo se presentan diversas aproximaciones empíricas para evaluar los efectos reales que conlleva el establecimiento de definiciones de servicios de banda ancha en el mercado de Internet fijo. Con base en los datos disponibles para Colombia sobre los planes de servicios de Internet fijo ofrecidos durante el periodo 2006-2012, se estima para los segmentos residencial y corporativo el proceso de difusión logístico modificado y el modelo de interacción estratégica para identificar los impactos generados sobre la masificación del servicio a nivel municipal y sobre las decisiones estratégicas que adoptan los operadores, respectivamente. Respecto a los resultados, se encuentra, por una parte, que las dos medidas regulatorias establecidas en Colombia en 2008 y 2010 presentan efectos significativos y positivos sobre el desplazamiento y el crecimiento de los procesos de difusión a nivel municipal. Por otra parte, se observa sustituibilidad estratégica en las decisiones de oferta de velocidad de descarga por parte de los operadores corporativos mientras que, a partir del análisis de distanciamiento de la velocidad ofrecida respecto al estándar mínimo de banda ancha, se demuestra que los proveedores de servicios residenciales tienden a agrupar sus decisiones de velocidad alrededor de los niveles establecidos por regulación.

Modelos estocásticos de crescimento individual e desenvolvimento de software de estimação e previsão

Os modelos de crescimento individual são geralmente adaptações de modelos de crescimento de populações. Inicialmente estes modelos eram apenas determinísticos, isto é, não incorporavam as flutuações aleatórias do ambiente. Com o desenvolvimento da teoria do cálculo estocástico podemos adicionar um termo estocástico, que representa a aleatoriedade ambiental que influencia o processo em estudo. Actualmente, o estudo do crescimento individual em ambiente aleatório é cada vez mais importante, não apenas pela vertente financeira, mas também devido às suas aplicações nas áreas da saúde e da pecuária, entre outras. Problemas como o ajustamento de modelos de crescimento individual, estimação de parâmetros e previsão de tamanhos futuros são tratados neste trabalho. São apresentadas novas aplicações do modelo estocástico monomolecular generalizado e um novo software de aplicação deste e de outros modelos. ABSTRACT: Individual growth models are usually adaptations of growth population models. Initially these models were only deterministic, that is, they did not incorporate the random fluctuations of the environment. With the development of the theory of stochastic calculus, we can add a stochastic term that represents the random environmental influences in the process under study. Currently, the study of individual growth in a random environment is increasingly important, not only by the financial scope but also because of its applications in health care and livestock production, among others. Problems such as adjustment of an individual growth model, estimation of parameters and prediction of future sizes are treated in this work. New applications of the generalized stochastic monomolecular model and a new software applied to this and other models are presented.

A review of models of spatial innovation infrastructures in support of high growth SMEs

This Paper first provides a review and analysis of the recent trends on innovation infrastructures developed in industrialised countries to promote innovation and competitiveness for high growth SMEs. It specifically aims to examine various spatial models developed to support provision of innovation infrastructure for high growth sector.

Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma

PURPOSE: Hreceptor (VEGFR) and FGF receptor (FGFR) signaling pathways. EXPERIMENTAL DESIGN: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. The effects of brivanib on apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to determine changes in proteins in these xenografts and cell lines. RESULTS: Brivanib significantly suppressed tumor growth in five of six xenograft lines. Furthermore, brivanib-induced growth inhibition was associated with a decrease in phosphorylated VEGFR-2 at Tyr(1054/1059), increased apoptosis, reduced microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these xenograft lines were positively correlated with its sensitivity to brivanib-induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation. CONCLUSION: This study provides a strong rationale for clinical investigation of brivanib in patients with HCC.

An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer

We investigated the effects of the matrix metalloproteinase 13 (MMP13)-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]phenoxy}phenoxy)-5-(2-methoxyethyl) pyrimidine-2,4,6(1H,3H,5H)-trione (Cmpd-1), on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis.

Electrochemical phase formation (ECPF): Nucleation growth vis-a-vis adsorption models

The nucleataon growth model of electrochemical phase formation is analysed for the hnear potential sweep input Apart from deducing diagnostic criteria and method~ of estimating model parameters, the predictions of the nucleation growth model are compared and contrasted with those of a sample adsorption model A dastlnCtlOn is made possible between adsorption and phase transition, which seems useful for understanding the nature of ECPF phenomena, especially underpotentlal deposition (UPD).

Electrochemical phase formation involving multicomponents: hemispherical overlap models for varied nucleation and growth conditions

The phenomenological theory of hemispherical growth in the context of phase formation with more than one component is presented. The model discusses in a unified manner both instantaneous and progressive nucleation (at the substrate) as well as arbitrary growth rates (e.g. constant and diffusion controlled growth rates). A generalized version of Avrami ansatz (a mean field description) is used to tackle the ''overlap'' aspects arising from the growing multicentres of the many components involved, observing that the nucleation is confined to the substrate plane only. The time evolution of the total extent of macrogrowth as well as those of the individual components are discussed explicitly for the case of two phases. The asymptotic expressions for macrogrowth are derived. Such analysis depicts a saturation limit (i.e. the maximum extent of growth possible) for the slower growing component and its dependence on the kinetic parameters which, in the electrochemical context, can be controlled through potential. The significance of this model in the context of multicomponent alloy deposition and possible future directions for further development are pointed out.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

OBJECTIVE: To examine the role of androgens on birth weight in genetic models of altered androgen signalling. SETTING: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). PATIENTS: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. MAIN OUTCOME MEASURES: Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. RESULTS: Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CONCLUSION: CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.