Cellular Automaton Model Research Papers (original) (raw)

Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of NO critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between the in vitro assay and in vivo studies, we report here a cellular model for screening NOS inhibitors. Stable transformants were generated by overexpressing rat neuronal NOS in HEK 293T cells. The enzyme was activated by introducing calcium into cells, and its activity was assayed by determining the amount of nitrite that was formed in culture media using the Griess reagent. We tested a few NOS inhibitors with this assay and found that the method is sensitive, versatile, and easy to use. The cell-based assay provides more information than in vitro assays regarding the bioavailability of NOS inhibitors, and it is suitable for high-throughput screening. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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- Analytical Chemistry, Calcium, Enzyme Inhibitors, Cell line

We report here on our latest developments in the forward and inverse problems of electrocardiology. In the forward problem, a coupled cellular model of cardiac excitation-contraction is embedded within an anatomically realistic model of the cardiac ventricles, which is itself embedded within a torso model. This continuum modelling framework allows the effects of cellular-level activity on the surface electrocardiogram (ECG) to be carefully examined. Furthermore, the contributions of contraction and local ischemia on body surface recordings can also be elucidated. Such information can provide theoretical limits to the sensitivity and ultimately the detection capability of body surface ECG recordings. Despite being very useful, such detailed forward modelling is not directly applicable when seeking to use densely sampled ECG information to assess a patient in a clinical environment (the inverse problem). In such a situation patient specific models must be constructed and, due to the nature of the inverse problem, the level of detail that can be reliably reproduced is limited. Extensive simulation studies have shown that the accuracy with which the heart is localised within the torso is the primary limiting factor. To further identify the practical performance capabilities of the current inverse algorithms, high quality experimental data is urgently needed. We have been working towards such an objective with a number of groups, including our local hospital in Auckland. At that hospital, in patients undergoing catheter ablation surgery, up to 256 simultaneous body surface signals were recorded by using various catheter pacing protocols. The geometric information required to customize the heart and torso model was obtained using a combination of ultrasound and laser scanning technologies. Our initial results indicate that such geometric imaging modalities are sufficient to produce promising inversely-constructed activation profiles.

- by Nicolas Smith
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- Algorithms, Electrophysiology, Ultrasound, Level Of Detail (LOD)

Suppose that a random process Z(s; t), indexed in space and time, has a spatio-temporal stationary covariance C(h; u), where h 2 IR d (d 1) is a spatial lag and u 2 IR is a temporal lag. Separable spatio-temporal covariances have the property that they can be written as a product of a purely spatial covariance and a purely temporal covariance. Their ease of de nition is counterbalanced by the rather limited class of random processes to which they correspond. In this article, we derive a new approach that allows one to obtain many classes of nonseparable, spatio-temporal stationary covariance functions and we t several such to spatio-temporal data on wind speed over a region in the tropical western Paci c ocean.

- by Hana Huang
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- Marketing, Chemical Engineering, Optical Engineering, Bioinformatics

An overview of the micromechanical theoretical and numerical models of wood is presented. Different methods of analysis of the effects of wood microstructures at different scale levels on the mechanical behaviour, deformation and strength of wood are discussed and compared. Micromechanical models of deformation and strength of wood are divided into three groups: cellular models (applied most often to the mesoscale or cell scale analysis of the wood deformation), continuum micromechanics and homogenization based methods, models which consider wood as a composite and are applied mainly to the analysis of wood at the microscale (cell wall scale) level and multiscale models. Lattice and composite models, which are used to analyze the damage and fracture of wood, are considered in a separate section. The areas of applicability and strong sides of each approach are discussed.

Simulações de crescimento urbano realizadas com cidades de pequeno porte têm mostrado diferenças das bordas de expansão em relação às demais partes da cidade, sendo que o potencial de crescimento se concentra nas interfaces do urbano com o não-urbano e do mais urbanizado com o menos urbanizado. Essa concentração tende a demarcar frentes de expansão em forma de linha, determinando uma borda com comportamento diferenciado do resto do sistema, onde podem ser observadas concentração e exclusão simultâneas, com células de elevado potencial de transformação e baixa centralidade. Essas frentes estão sendo estudadas em simulações com cidades do sul do Brasil, utilizando técnicas de autômato celular, através do software CityCell, desenvolvido pelo Laboratório de Urbanismo da UFPel. Sendo assim, este trabalho apresenta uma síntese sobre as simulações de crescimento e os resultados que vêm sendo alcançados.

- by Lucas Aragão
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- Urban Planning, Modeling and Simulation, Cellular Automata, Borders and Frontiers

Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual-system and multiple-system vulnerability to stressors, development of animal and cellular models, application of population-based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more-targeted research agenda-setting process.

- by Luigi Ferrucci
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- Genetics, Geriatrics, Aging, Pathophysiology
- by Tanvir Tan
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- Management, Marketing, Biochemistry, Cultural Studies
- by Slava Kalyuga
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- Management, Marketing, Engineering, Ecological Engineering

In this paper, we review and analyze the emerging network paradigm in organizational research. We begin with a conventional review of recent research organized around recognized research streams. Next, we analyze this research, developing a set of dimensions along which network studies vary, including direction of causality, levels of analysis, explanatory goals, and explanatory mechanisms. We use the latter two dimensions to construct a 2-by-2 table cross-classifying studies of network consequences into four canonical types: structural social capital, social access to resources, contagion, and environmental shaping. We note the rise in popularity of studies with a greater sense of agency than was traditional in network research.

- by Steve Borgatti
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- Management, Marketing, Biochemistry, Cryobiology

The microstructure and texture of rolled and annealed dual-phase steels with 0.147 wt. % C, 1.868 wt. % Mn, and 0.403 wt. % Si were analyzed using SEM, EDX, and EBSD. Hot rolled sheets showed a ferritic-pearlitic microstructure with a pearlite volume fraction of about 40 % and ferrite grain size of about 6 µm. Ferrite and pearlite were heterogeneously distributed at the surface and distributed in bands at the center of the sheets. The hot rolled sheets revealed a throughthickness texture inhomogeneity with a plane-strain texture with strong α-fiber and γ-fiber at the center and a shear texture at the surface. After cold rolling, the ferrite grains showed elongated morphology and larger orientation gradients, the period of the ferrite-pearlite band structure at the center of the sheets was decreased, and the plane-strain texture components were strengthened in the entire sheet. Recrystallization, phase transformation, and the competition of both processes were of particular interest with respect to the annealing experiments. For this purpose, various annealing techniques were applied, i.e., annealing in salt bath, conductive annealing, and industrial hot-dip coating. The sheets were annealed in the ferritic, intercritical, and austenitic temperature regimes in a wide annealing time range including variation of heating and cooling rates.

- by Dierk Raabe
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- Phase Transformations, Cellular Automata, Recrystallization, Cellular Automaton Model

The ISO 9001 (2000) define "Quality" as the ability of a set of inherent properties and characteristics of a product, system or process to fulfill requirements of customers and other interested parties. The "Plan de Calidad de Obra (PCO)" is an instrument that follows to get the necessary quality in Civil Works contracts. Graphical documentation generated during construction project elaboration or even during Civil Engineering works execution with planes, makes obligatory a meticulous treatment of this information that results transcendental in the consecution of the definitive products (projects or works) quality objective. In this work it's shown the principal graphical documentation procedures defined in the PCO attending to the edition, modification, distribution, storage, and other relevant aspects related to graphical information.

- by luis chavez
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- Management, Marketing, Engineering, Ecological Engineering
- by Laura Stovel
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- Marketing, Chemical Engineering, Optical Engineering, Bioinformatics
- by Virginia Butler
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- Engineering, Optical Engineering, Biochemistry, Bioinformatics
- by Bonnie Zare
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- Management, Marketing, Engineering, Ecological Engineering
- by Caryl Sortwell
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- Inflammation, Multidisciplinary, Dopamine, Neurons

The paper presents a two-dimensional approach for simulating primary static recrystallization, which is based on coupling a viscoplastic crystal plasticity finite-element model with a probabilistic kinetic cellular automaton. The crystal plasticity finite-element model accounts for crystallographic slip and for the rotation of the crystal lattice during plastic deformation. The
model uses space and time as independent variables and the crystal orientation and the accumulated slip as dependent variables. The ambiguity in the selection of the active slip systems is avoided by using a viscoplastic formulation that assumes that the slip rate on a slip system is related to the resolved shear stress through a power-law relation. The equations are cast in an updated Lagrangian framework. The model has been implemented as a user subroutine in the commercial finite-element code Abaqus. The cellular automaton uses a switching rule that is formulated as a probabilistic analogue of the linearized symmetric Turnbull kinetic equation for the motion of sharp
grain boundaries. The actual decision about a switching event is made using a simple sampling nonMetropolis Monte Carlo step. The automaton uses space and time as independent variables and
the crystal orientation and a stored energy measure as dependent variables. The kinetics produced by the switching algorithm are scaled through the mesh size, the grain boundary mobility, and the driving force data. The coupling of the two models is realized by: translating the state variables used
in the finite-element plasticity model into state variables used in the cellular automaton; mapping the finite-element integration point locations on the quadratic cellular automaton mesh; using the resulting cell size, maximum driving force, and maximum grain boundary mobility occurring in the region for determining the length scale, time step, and local switching probabilities in the automaton; and identifying an appropriate nucleation criterion. The coupling method is applied to the two-dimensional simulation of texture and microstructure evolution in a heterogeneously
deformed, high-purity aluminium polycrystal during static primary recrystallization, considering local grain boundary mobilities and driving forces.

The post-dynamic transformation that takes place during the subsequent isothermal holding for the case when dynamic strain-induced transformation (DSIT) from austenite to ferrite occurs during hot deformation is investigated by cellular automaton modeling. The simulation provides a better understanding of carbon diffusion in retained austenite and the resulting microstructure evolution during the post-dynamic transformation. The predictions reveal that continuing transformation from retained austenite to ferrite and the reverse transformation can occur simultaneously in the same microstructure during post-deformation isothermal holding owing to the locally acting chemical equilibrium conditions. Competition between forward and reverse transformation exists during the early stage of post-dynamic heat treatment. It is also revealed that increasing the final strain of DSIT might promote the reverse transformation, whereas the continuous austenite-to-ferrite transformation yields a diminishing effect. The influence of the DSIT final strain on the grain size of ferrite and the characteristics of the resultant microstructure is also discussed.

Pathogens and eucaryotic cells are active partners during the process of pathogenicity. To gain access to enterocytes and to cross the epithelial membrane, many enterovirulent microorganisms interact with the brush border membrane-associated components as receptors. Recent reports provide evidence that intestinal cell differentiation plays a role in microbial pathogenesis. Human enteropathogenic Escherichia coli (EPEC) develop their pathogenicity upon infecting enterocytes. To determine if intestinal epithelial cell differentiation influences EPEC pathogenicity, we examined the infection of human intestinal epithelial cells by JPN 15 (pMAR7) [EAF+ eae+] EPEC strain as a function of the cell differentiation. The human embryonic intestinal INT407 cells, the human colonic T,, cells, the human undifferentiated HT-29 cells (HT-29 Std) and two enterocytic cell lines, HT-29 glc-/+ and Caco-2 cells, were used as cellular models. Cells were infected apically with the EPEC strain and the cell-association and cellentry were examined by quantitative determination using metabolically radiolabeled bacteria, as well as by light, scanning and tranmission electron microscopy. [EAF+ eae+] EPEC bacteria efficiently colonized the cultured human intestinal cells. Diffuse bacterial adhesion occurred to undifferentiated HT-29 Std and INT407 cells, whereas characteristic EPEC cell clusters were observed on fully differentiated enterocytic HT-29 glc-/+ cells and on colonic crypt T,, cells. As shown using the Caco-2 cell line, which spontaneously differentiates in culture, the formation of EPEC clusters increased as a function of the epithelial cell differentiation. In contrast, efficient cell-entry of [EAF+ eae+] EPEC bacteria occured in recently differentiated Caco-2 cells and decreased when the cells were fully differentiated. Our results provide evidence that the intestinal cell differentiation could play a dual role in EPEC pathogenesis: it up-regulates intestinal cell colonization and down-regulates intestinal cell invasion.

- by Jim Kaper
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- Electron Microscopy, Cell line, In Vitro, Cell Differentiation

Huntington's disease (HD) is a neurodegenerative disorder resulting from the expansion of a glutamine repeat (polyQ) in the N-terminus of the huntingtin (htt) protein. Expression of polyQ-containing proteins has been previously shown to induce various cellular stress responses. Among these, activation of the c-Jun Nterminal kinase (JNK) cascade has been observed in cellular models of HD. However, the implication of the JNK pathway has not previously been evaluated in the striatum of HD animal models. Here we report that the JNK pathway participates in HD pathology in a rat model of the disease. Increased phosphorylation of the JNK target c-Jun was observed as early as 4 weeks and persisted for 13 weeks after lentiviral-mediated expression of htt171-82Q. In order to assess the importance of this pathway in HD pathology, JNK inhibitors including dominant-negative mutants of upstream kinases (ASK1 K709R , MEKK1 D1369A ), a c-Jun mutant (Δ169c-Jun) and the active domain of the scaffold protein JIP-1/IBI (IBI-JBD) were tested for their ability to mitigate the effect of htt171-82Q. The overexpression of MEKK1 D1369A and JIP-1/IBI reduced the polyQ-related loss of DARPP-32 expression, while the other inhibitors had no effect. In all cases, the formation of EM48-positive htt inclusions and P-c-Jun immunoreactivity were unaltered. These results suggest that JNK activation is involved in HD and that blockade of this pathway may be of benefit in counteracting HD-related neurotoxicity.

- by Nicole Déglon
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- Psychology, Signal Transduction, Dopamine, Mutation

Abbreviations: cybrid = osteosarcoma-derived cytoplasmic hybrid; DHK = dihydrokainic acid; EAAT = excitatory amino acid transporter; LABH = L-aspartate-b-hydroxamate; LHON = Leber hereditary optic neuropathy; Km = glutamate uptake affinity; mtDNA = mitochondrial DNA; ROS = reactive oxygen species; Vmax = glutamate uptake maximal velocity; SOS = L-serine-Osulphate; THA = L-(-)-threo-3-hydroxyaspartic acid.

- by Simone Beretta
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- Genetics, Death, Free Radicals, Energy Metabolism

GLP-1 (glucagon-like peptide-1) is a potent insulin secretagogue released from L cells in the intestine. The regulation of GLP-1 secretion has been described both in vivo and in vitro in several animal species, but data from human cellular models are lacking. For this purpose, factors and cell-signaling pathways regulating GLP-1 secretion were investigated in the NCI-H716 human intestinal cell line. After differentiation, these cells homogeneously produced 16.8 pmol GLP-1/mg protein with a basal release of 4.2% during a 2-h incubation period. Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neu-romediator gastrin-releasing peptide. Along with stimulating GLP-1 release, gastrin-releasing peptide, like ionomycin, increased intracellular calcium levels. Activators of PKA and PKC were able to increase GLP-1 secretion in NCI-H716 cells. However, neither PKA activators nor meat hydrolysate increased proglucagon mRNA levels. These findings indicate that the NCI-H716 cell line constitutes a unique model to study the cellular mechanism of GLP-1 secretion in humans and suggest potential interspecies divergence in the regulation of proglucagon gene expression in enteroendocrine cells.

- by Raylene Reimer
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- Endocrinology, Diet, Cell Signaling, Gene expression

Nature ©2007 Publishing Group and BMAL1. In all assays, CRY1-mediated repression on the CLOCK-BMAL1(K537R) dimer was reduced with respect to CLOCK-BMAL1 by 3-5-fold. c, BMAL1 acetylation facilitates association of CRY1 with CLOCK-BMAL1. CLOCK-BMAL1 interaction with CRY1 was tested by co-immunoprecipitation. Expression vectors for Myc-CRY1-Flag (300 ng) and Myc-GFP (2,000 ng) (lane1), Myc-CRY1-Flag (100 ng), Myc-CLOCK (3,000 ng) and VP16-BMAL1(WT) (3,000 ng) (lane 2), Myc-CRY1-Flag (100 ng), Myc-CLOCK (3,000 ng), and VP16-BMAL1(K537R) (3,000 ng) (lane 3), or Myc-CRY1-Flag (100 ng), Myc-CLOCK (3,000 ng), and VP16-BMAL1(K538R) (3,000 ng) (lane 4) were co-transfected in JEG3 cells. Lysates were immunoprecipitated with anti-Flag antibody. Immunoprecipitates and total cell lysates were analysed by immunoblotting with anti-BMAL1 antibody (BMAL1) or anti-Myc antibody (CLOCK, GFP and CRY1).

- by Ken Takamatsu
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- Biochemistry, Bioinformatics, Developmental Biology, Climate Change

An ecomorphological analysis of the skeletal remains of large canids, Canis ( Xenocyon ) falconeri and Canis etruscus (Mammalia, Carnivora, Canidae), preserved in an assemblage of large mammals from the lower Pleistocene site at Venta Micena (Guadix-Baza Basin, Orce, Granada, southeastern Spain) is reported. Mean body mass of adult individuals was estimated to be around 10 kg for C. etruscus and approximately 28 kg for C. falconeri using multiple regression. A comparative study of tooth measurements in modern canids, using principal components and discriminant function analysis, infers quite different ecomorphological adaptations and feeding behavior for both fossil species. The craniodental morphology of C. falconeri is similar to that shown by extant hypercarnivorous canids whose diet include more than 70% of vertebrate meat, whereas C. etruscus shows a cranial morphology similar to those of modern omnivorous species, thus indicating a dietary niche in which vertebrate meat represented less than 70% of its diet, with other feeding resources making up the balance. These results suggest that there was a marked ecological segregation between both sympatric species of large canids. The find of a complete skull of C. falconeri showing bilateral asymmetry and marked dental anomalies could suggest high levels of genetic homozygosis in the population which inhabited this region during early Pleistocene times, possibly as a consequence of isolation and the low number of individuals. This may have subsequently led to the extinction of C. falconeri in the Western fringe of Europe. The survival of this pathological individual to adulthood indicates that this species may have developed cooperative behavior similar to that of modern African wild dogs. 0 C ANIS ( X ENOCYON ) FALCONERI , C ANIS ETRUSCUS , ecomorphology, principal component analysis, discriminant analysis, cranial fluctuating asymmetry, Venta Micena, lower Pleistocene. Paul Palmqvist [ Paul.Palmqvist@uma.es ] ,

- by Paul Barrena and +1
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- Management, Marketing, Biochemistry, Cryobiology

Therapeutic interventions for the prodromal stages of dementia are currently being sought with a view to delaying if not preventing disease onset. Uncertainty as to whether cognitive disorder in a given individual will progress towards dementia and adverse drug side-effects has led to hesitancy on the part of drug regulators to instigate preventive pharmacotherapies.

- by Yves Christen and +1
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- Cognitive Science, Mild Cognitive Impairment, Flavonoids, Wine

A cellular model of the primate retina has been developed. Unlike existing models, it incorporates spatial non-uniformities, such as the random arrangement of L and M cones, and the radial dilation with eccentricity. Based on a population of ganglion cell activities, colour-image representation is modelled with the luminance and the R-G opponent channels. The developed model reproduces experimentally known properties in temporal and spatial vision. Furthermore, spatio-temporally coupled properties such as transition from positive to negative phases in an afterimage, are recapped. In colour vision, the model can explain the insensitivity in our colour perception to the L/M cone ratio.

- by Mark Hankins
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- Psychophysics, Colour Vision, Spatial vision, Color Perception

This study presents crystal-plasticity finite-element calculations of room temperature deformation of a single-crystal nickel-base superalloy and simulation results on the microstructural development during subsequent recrystallization. The predictions are compared to corresponding experiments. Single-crystalline material is deformed by Brinell-type indentation using a spherical indenter of 1mm in diameter. A succeeding annealing under inert atmosphere leads to the formation of recrystallized grains around the indents. The crystal plasticity finite element method is used to predict the distribution of crystallographic slip around the indents. The amount of accumulated slip is used to estimate the stored deformation energy in the indented volume. A 2D probabilistic cellular automaton simulation is then applied to the predicted distribution of the stored energy for the simulation of the formation and growth of new grains around the indents. The cellular automaton predicts the kinetics, microstructures, and crystallographic texture evolving during recrystallization.

- by Dierk Raabe
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- Cellular Automata, Superalloys, Ni Based Superalloys, Nickel base superalloys

Although common among bacteria, lateral gene transfer-the movement of genes between distantly related organisms-is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of 4 insect and 4 nematode species that range from nearly the entire Wolbachia genome (>1 megabase) to short (<500 base pairs) insertions. Potential Wolbachia to host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.

- by Daniele Pereira de Oliveira
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- Engineering, Optical Engineering, Biochemistry, Bioinformatics

This study examines the extent to which fish remains are affected by digestive processes and includes experimental and comparative analysis of tui chub (Cyprinidae: Gila bicolor) fish remains from modern human feeding experiments, modem coyote scats and archaeological human coprolites. Body part representation varies across the samples, but overall, bone loss resulting from digestive process is less than that documented for fish remains in previous studies. Selected elements are examined for surface modifications (pitting, rounding, adhering tissue, staining, deformation) and degree of completeness. Results show that digestive processes often modify specimens, but that many remains are unaffected. Remains that pass through human and coyote digestive tracts are similarly modified, thus distinguishing fish remains generated by the two agents is not possible using the attributes described. A sample of fish remains from western Nevada is examined for surface modification and specimen completeness to determine whether the fish ren1ains were modified by digestive agents. Results show that at least some of the fish fauna had been ingested by mammals.

- by Virginia Butler
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- Engineering, Optical Engineering, Biochemistry, Bioinformatics
- by Jim Specht
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- Management, Marketing, Biochemistry, Cultural Studies

Three glycosilated flavonoids (diosmin, hesperidin and naringin) and respective aglycones were characterized in terms of their apparent ionisation constants and bidirectional permeability using the cellular model Caco-2 as well as the artificial membrane model PAMPA. Ionisation curves were established by capillary electrophoresis. It was confirmed that significant amounts of the aglycones are ionised at physiological pH whereas the glycosides are in the neutral form. Permeation was not detected for the glycosides in either the apical to basolateral or basolateral to apical directions confirming the need for metabolism before absorption through the intestinal membrane. The aglycones permeated in both directions with apparent permeabilities (P app ) in the range of 1-8 · 10 À5 cm/s. The results from both in vitro methods correlated providing some evidence of passive transport however the hypothesis of active transport can not be excluded particularly in the case of diosmetin. Metabolism of the aglycones was detected with the cell model, more extensively when loading in the apical side. Some of the metabolites were identified as glucuronide conjugates by enzymatic hydrolysis.

Many biological phenomena are inherently multiscale, i.e. they are characterised by interactions involving different scales at the same time. This is the case of bone remodelling, where macroscopic behaviour (at organ and tissue scale) and microstructure (at cell scale) strongly influence each other. Consequently, several approaches have been defined to model such a process at different spatial and temporal levels and, in particular, in terms of continuum properties, abstracting in this way from a realistic -and more complex -cellular scenario. While a large amount of information is available to validate such models separately, more work is needed to integrate all levels fully in a faithful multiscale model. In this scenario, we propose the use of BioShape, a 3D particle-based, scale-independent, geometry and space oriented simulator. It is used to define and integrate a cell and tissue scale model for bone remodelling in terms of shapes equipped with perception, interaction and movement capabilities. Their in-silico simulation allows for tuning continuum-based tissutal and cellular models, as well as for better understandingboth in qualitative and in quantitative terms -the blurry synergy between mechanical and metabolic factors triggering bone remodelling.

- by Emanuela Merelli and +1
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- Cognitive Science, Multiscale Modeling, Multiscale Modelling, Computer Software

One of the hallmarks of breast adenocarcinomas is the over expression and aberrant localization of membranebound mucins, such as MUC1 and MUC4 . Mucins are characterized by a large number of tandem repeated domains, rich in serine and... more

- by Sylvain Julien and +2
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- Breast Cancer, Cell Adhesion, Cellular Automaton Model, Prognosis

Studies at the basic and clinical levels demonstrate that neuronal atrophy and cell death occur in response to stress and in the brains of depressed patients. Although the mechanisms have yet to be fully elucidated, progress has been made in characterizing the signal transduction cascades that control neuronal atrophy and programmed cell death and that may be involved in the action of antidepressant treatment. These pathways include the cyclic adenosine monophosphate and neurotrophic factor signal transduction cascades. It is notable that these same pathways have been demonstrated to play a pivotal role in cellular models of neural plasticity. This overlap of plasticity and cell survival pathways, together with studies demonstrating that neuronal activity enhances cell survival, suggests that neuronal atrophy and death could result from a disruption of the mechanisms underlying neural plasticity. The role of these pathways and failure of neuronal plasticity in stress-related mood disorders are discussed.

- by Jessica Malberg
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- Signal Transduction, Biological Sciences, Biological Psychiatry, Cell Death

Global climate and environmental change studies require detailed land-use and land-cover (LULC) information about the past, present, and future. In this paper, we discuss a methodology for downscaling coarse-resolution (i.e., half-degree) future land use scenarios to finer (i.e., 1 km) resolutions at the global scale using a grid-based spatially explicit cellular automata (CA) model. We account for spatial heterogeneity from topography, climate, soils, and socioeconomic variables. The model uses a global 30 m land cover map (2010) as the base input, a variety of biogeographic and socioeconomic variables, and an empirical analysis to downscale coarse-resolution land use information (specifically urban, crop and pasture). The output of this model offers the most current and finest-scale future LULC dynamics from 2010 to 2100 (with four representative concentration pathway (RCP) scenarios—RCP
2.6, RCP 4.5, RCP 6.0, and RCP 8.5) at a 1 km resolution within a globally consistent framework. The data are freely available for download, and will enable researchers to study the impacts of LULC change at the local scale.

- by Terry Sohl
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- Cellular Automata, Land Use Change, Land use and land cover change modeling, Land Use

The development of nanotechnologies may lead to dissemination of potentially toxic nanoparticles in the environment. Toxicology of these nano-sized particles is thus attracting attention of public and governments worldwide. Our research is focused on the in vitro response of eukaryotic cells to nanoparticles exposure. For this purpose, we used cellular models of primary target organs (lung: A549 alveolar epithelial cells), or secondary target organs (liver: WIF-B9, Can-10 and kidneys: NRK-52E, LLC-PK1 proximal cells), i.e., organs exposed if nanoparticles are translocated through epithelial barriers. These cells were exposed to TiO 2 , SiC nanoparticles or multi-walled carbon nanotubes (MWCNT). The influence of nanoparticles physicochemical characteristics on various toxicological endpoints (cytotoxicity, reactive oxygen species generation, genotoxicity) was specified. Our data demonstrate that nanoparticles toxicity depend on their size, morphology, and chemical composition, the finest, spherical shaped, and anatase TiO 2 nanoparticles being the more cytotoxic to NRK-52E cells, while SiC nanoparticles exert almost no cytotoxicity. MWCNT cytotoxicity neither depended on their length, nor on the presence of metal impurities. Nanoparticles cytotoxicity also depended on the exposed cell line. All the tested nanoparticles were uptaken by cells and caused intracellular reactive oxygen species generation. Relative to genotoxic effects, DNA strand breaks were detected in NRK-52E cells via the alkaline comet assay after exposure of cells to TiO 2 nanoparticles and to a lesser extent after exposure to MWCNT, but no double strand breaks were detected. The originality of this study lies on the panel of nanomaterials which were tested on a variety of cell lines. All these data may lead to a better understanding of nanomaterial toxicity and hazards for health.

- by Nathalie Herlin-boime
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- Materials Engineering, General Relativity, Nanoparticle, Nanomedicine

This paper is an attempt to develop software framework for public library based and Webenabled multilingual community information services by utilizing open standards and open source software. It uses GSDL as DL software, PERL, PHP and Java as programming environment, Unicode as character encoding standard, SeamlessUK Application Profile as metadata schema, RFC-2731 as metadata encoding standard, and an array of FLOSS based multilingual tools for designing Bengali script based user interface, processing and retrieval environment.

- by Parthasarathi Mukhoapdhyay
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- Management, Marketing, Engineering, Ecological Engineering

The insulin-like growth factor I receptor (IGF1-R) system has long been implicated in cancer and is a promising target for tumor therapy. Besides in vitro screening assays, the discovery of specific inhibitors against IGF-1R requires relevant cellular models, ideally applicable to both in vitro and in vivo studies. With this aim in mind, the authors generated an inducible cell line using the tetracycline-responsive gene expression system to mimic the effects of therapeutic inhibition of the IGF-1R both in vitro and on established tumors in vivo. Inducible overexpression of IGF-1R in murine embryonic fibroblasts was achieved and resulted in the transformation of the cells as verified by their ability to grow in soft agar and in nude mice. Continuous repression of exogenous IGF-1R expression completely prevented outgrowth of the tumors. Furthermore, induced repression of IGF-1R expression in established tumors resulted in regression of the tumors. Interestingly, however, IGF-1R-independent relapse of tumor growth was observed upon prolonged IGF-1R repression. The IGF-1R cell line generated using this approach was successfully employed to test reference small-molecule inhibitors in vitro and an IGF-1R-specific inhibitory antibody, EM164, in vivo. Besides efficacy as a read-out, phospho-AKT could be identified as a pharmacodynamic biomarker, establishing this cell line as a valuable tool for the preclinical development of IGF-1R inhibitors.

- by M. Chiron and +1
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- Drug Discovery, Gene expression, Cell line, Mice

We investigated the mechanisms underlying severe bleeding occurring upon consumption of Ferula communis. The prenylated coumarin ferulenol extracted from this plant did not directly affect blood coagulation but showed hepatocyte cytotoxicity and, at non-cytotoxic concentrations (b100 nM), impaired factor X biosynthesis (40% reduction). Studies with ferulenol derivatives indicated the prenyl residue as major determinant of ferulenol activity.

- by Giovanni Appendino
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- Biological Sciences, Cell line, Physical sciences, Blood Coagulation

A two-dimensional lattice Boltzmann-cellular automaton model is coupled with the CALPHAD (Calculation of Phase Diagrams) method for simulating dendritic growth during ternary alloy solidification with convection. In the model, the kinetics of dendritic growth is determined by the difference between the equilibrium liquidus temperature and the actual temperature at the solid/liquid interface, incorporating the effects of the interface curvature and the preferred dendritic growth orientation. The lattice Boltzmann method is used for evaluating the local liquid compositions of the two solutes impacted by diffusion and convection. Based on the local liquid compositions, the equilibrium liquidus temperature and the solid concentrations of the two solutes are obtained by the CALPHAD method. The model is applied to simulate dendritic growth of an Al–4 wt-%Cu–1 wt-%Mg ternary alloy with melt convection. The results demonstrate the high numerical convergence and stability, as well as computational efficiency, of the proposed model. Melt convection is found to influence the dendritic morphologies and microsegregation patterns in the solidification of ternary alloys.

A spatial model was used to simulate plant extinction in relation to prescribed burning in fire-prone shrublands. Prescribed burning may be used to manipulate fuel to levels that are sub-critical for fire-spread in extreme weather. Effects of variation in area of annual prescribed burning on area of unplanned fires occurring under severe weather and the probability of extinction in three functional groups of shrubs (serotinous and leguminous obligate seeders and serotinous resprouters) were examined. Results of 200 year simulations indicated that restriction of the size of unplanned fires occurred when large (> 30%) areas of the landscape were burnt annually. Risk of extinction in obligate seeders was high at such levels of prescribed burning. Extinction probability was also positively related to frequency of unplanned fires. In resprouters, risk of extinction was unaffected by prescribed fire. The model predicts that passive restriction of unplanned fires in extreme weather, by prescribed burning, is incompatible with floristic conservation objectives.

- by James Scott
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- Prescribed Fire, Biological Sciences, Environmental Sciences, Biological Conservation
- by Leo Yeung
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- Management, Marketing, Engineering, Ecological Engineering

We aimed to determine the effectiveness of a lay-administered tailored education and coaching (TEC) intervention (aimed at reducing pain misconceptions and enhancing self-efficacy for communicating with physicians) on cancer pain severity, pain-related impairment, and quality of life. Cancer patients with baseline ''worst pain'' of P4 on a 0-10 scale or at least moderate functional impairment due to pain were randomly assigned to TEC or enhanced usual care (EUC) during a telephone interview conducted in advance of a planned oncology office visit (265 patients randomized to TEC or EUC; 258 completed at least one follow-up). Patients completed questionnaires before and after the visit and were interviewed by telephone at 2, 6, and 12 weeks. Mixed effects regressions were used to evaluate the intervention adjusting for patient, practice, and site characteristics. Compared to EUC, TEC was associated with increased pain communication self-efficacy after the intervention (P < .001); both groups showed significant (P < .0001), similar, reductions in pain misconceptions. At 2 weeks, assignment to TEC was associated with improvement in pain-related impairment (À0.25 points on a 5-point scale, 95% confidence interval À0.43 to À0.06, P = .01) but not in pain severity (À0.21 points on an 11-point scale, À0.60 to 0.17, P = .27). The improvement in pain-related impairment was not sustained at 6 and 12 weeks. There were no significant intervention by subgroup interactions (P > .10). We conclude that TEC, compared with EUC, resulted in improved pain communication self-efficacy and temporary improvement in pain-related impairment, but no improvement in pain severity. Ó

- by Emilie d'Orgeix
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- Management, Marketing, Engineering, Ecological Engineering
- by Bruno Van der Linden
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- Management, Marketing, Biochemistry, Cultural Studies

el valioso aporte en cada una de las etapas del modelo a partir de su génesis a inicios del año 2002. Hacemos especial mención a David Vavra y Jeromer Benes por su valiosa colaboración. Las opiniones vertidas en este documento son responsabilidad exclusiva de los autores y no reflejan necesariamente la visión del BCR. 1 Los dos principales aportes hechos por esta comisión a la econometría son el impulsar el uso de la inferencia estadística en economía así como desarrollar, estimar, identificar y tratar de validar modelos macroeconómicos de ecuaciones simultáneas.

- by Marco Vega
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- Management, Marketing, Biochemistry, Cultural Studies

Chrysanthemum indicum Linn. (CI) has been used in Oriental medicine for several centuries. In the present study, the effect of CI extract was evaluated against 1-methyl-4-phenylpridinium ion (MPP + )-induced damage in SH-SY5Y cells and lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Cell viability, oxidative damage, reactive oxygen species, expression of Bcl-2/Bax, and poly (ADP-ribose) polymerase (PARP) proteolysis were evaluated using SH-SY5Y cells. Production of iNOS, prostaglandin E 2 , and pro-inflammatory cytokines like tumor necrosis factor (TNF)-a, interleukin (IL)-1b, interleukin (IL)-6, expression of cyclooxygenase type-2 (COX-2) and type-1 (COX-1) were examined in activated BV-2 microglia. At 1, 10 and 100 lg, CI inhibited cell loss, decreased the reactive oxygen species production, regulated the Bax/Bcl-2 ratio and inhibited PARP proteolysis in MPP + -induced SH-SY5Y cells. Furthermore, CI suppressed the production of prostaglandin E 2, expression of cyclooxygenase type-2 (COX-2), blocked IjB-a degradation and activation of NF-jB p65 in BV-2 cells in a dose-dependent manner. The molecular mechanisms involved by CI might involve its inhibitory actions both on neuronal apoptosis and neuroinflammatory NF-jB/IjB-a signaling pathway. The present investigation scientifically supports the long history and safe usage of CI as an important functional food with potential benefits in ameliorating deleterious conditions seen in PD.

- by Sushruta Koppula
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- Flow Cytometry, Cytokines, Oxidative Stress, Apoptosis

Background: Clinical studies have demonstrated beneficial outcomes for low-level laser therapy (LLLT) using near-infrared (NIR) wavelengths. It has been hypothesized that the benefits of NIR LLLT are due in part to the thermal effects of NIR exposure. However, it is not clear whether photochemical interactions between NIR light and superficial tissues contribute to beneficial outcomes. To investigate the photochemical effects of NIR exposure, the efficacy of 980 nm NIR LLLT on human fibroblast growth rates is investigated using an in vitro model of wound healing.

- by Mark Skopin
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- Wound Healing, Near Infrared, Lasers, Clinical Sciences

Interference is one of the main performance limiting factors in the use of femtocells in conventional cellular radio networks. We develop a femtocell power control scheme that relies on minimal coordination with the macrocell base station. The power control is used in conjunction with an interference sensing channel assignment mechanism. Using these two schemes we show gains over 100% in sum rate. We then develop a technique for macro users to join a nearby femtocell and share a common channel with a femtocell user through the use of successive interference cancellation. By adding this mechanism to the power control and channel assignment schemes, we show gains over 200% in sum rate and power savings up to 90% for macro cell users.

- by Jorma Lilleberg
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- Silicon Carbide, Power Control, Cellular Automaton Model, Power Saving

Anodic spark deposition (ASD) is an attractive technique for improving the implant-bone interface that can be applied to titanium and titanium alloys. This technique produces a surface with microporous morphology and an oxide layer enriched with calcium and phosphorus. The aim of the present study was to investigate the biological response in vitro using primary human osteoblasts as a cellular model and the osteogenic primary response in vivo within a short experimental time frame (2 and 4 weeks) in an animal model (rabbit). Responses were assessed by comparing the new electrochemical biomimetic treatments to an acid-etching treatment as control. The in vitro biological response was characterized by cell morphology, adhesion, proliferation activity and cell metabolic activity. A complete assessment of osteogenic activity in vivo was achieved by estimating static and dynamic histomorphometric parameters at several time points within the considered time frame. The in vitro study showed enhanced osteoblast adhesion and higher metabolic activity for the ASD-treated surfaces during the first days after seeding compared to the control titanium. For the ASD surfaces, the histomorphometry indicated a higher mineral apposition rate within 2 weeks and a more extended bone activation within the first week after surgery, leading to more extensive bone-implant contact after 2 weeks. In conclusion, the ASD surface treatments enhanced the biological response in vitro, promoting an early osteoblast adhesion, and the osteointegrative properties in vivo, accelerating the primary osteogenic response.

- by A. Cacchioli
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- Tissue Engineering, Titanium, Treatment Outcome, Crystallization

Extensos estudios celulares y conductuales han llevado a la postulacion de que la memoria es codificada por cambios en la fuerza sinaptica entre las neuronas, como lo ha demostrado la correlacion entre los cambios a largo plazo en la conducta de los animales y en las conexiones neuronales que generan una conducta especifica, en animales invertebrados o vertebrados, en los que los modelos celulares de plasticidad sinaptica, usando aproximaciones geneticas como el fenomeno de potenciacion de largo plazo (LTP), o el fenomeno de la depresion de largo plazo (LTD), han demostrado que dependen de cambios a largo plazo en la actividad sinaptica implicada en las conductas de aprendizaje y memoria. La memoria de largo plazo (LTM) es crucial para la sobrevivencia de los animales y representa un mecanismo fundamental para los eventos neurobiologicos en el sistema nervioso de las especies de vertebrados e invertebrados, incluyendo el del humano. Los cambios a largo plazo en la conectividad sinap...

- by Adriana Arias Caballero
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- Genetics, Long Term Potentiation, Gene regulation, Synaptic Plasticity

The presence of aggregates of abnormally expanded polyglutamine (polyQ)-containing proteins are a pathological hallmark of a number of neurodegenerative diseases including Huntington's disease (HD) and spinocerebellar ataxia-3 (SCA3). Previous studies in cellular, Drosophila, and mouse models of HD and SCA have shown that neurodegeneration can be prevented by manipulations that inhibit polyQ aggregation. We have shown that the UL97 kinase of the human cytomegalovirus (HCMV) prevents aggregation of the pp71 and pp65 viral tegument proteins. To explore whether UL97 may act as a general antiaggregation factor, we examined whether UL97 prevents aggregation of cellular non-polyQ and polyQ proteins. We report that UL97 prevents the deposition of aggregates of two non-polyQ proteins: a protein chimera (GFP170*) composed of the green fluorescent protein and a fragment of the Golgi Complex protein (GCP-170) and a chimera composed of the red fluorescent protein (RFP) fused to the Werner syndrome protein (WRN), a RecQ helicase and exonuclease involved in DNA repair. Furthermore, we show that UL97 inhibits aggregate deposition in cellular models of HD and SCA3. UL97 prevents the deposition of aggregates of the mutant huntingtin exon 1 containing 82 glutamine repeats (HttExon1-Q82) or full length ataxin-3 containing a 72 polyQ track (AT3-72Q). The kinase activity of UL97 appears critical, as the kinase-dead UL97 mutant (K335M) fails to prevent aggregate formation. We further show that UL97 disrupts nuclear PML bodies and decreases p53-mediated transcription. The universality of the antiaggregation effect of UL97 suggests that UL97 targets a key cellular factor that regulates cellular aggregation mechanisms. Our results identify UL97 as a novel means to modulate polyQ aggregation and suggest that UL97 can serve as a novel tool to probe the cellular mechanisms that contribute to the formation of aggregates in polyglutamine disorders.

- by Lianwu Fu and +1
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- Neurobiology Of Disease, DNA repair, Mutation, Spinocerebellar ataxia