A genomewide survey of developmentally relevant genes in Ciona intestinalis - IV. Genes for HMG transcriptional regulators, bZip and GATA/Gli/Zic/Snail

Many kinds of transcription factors and regulators play key roles in a variety of developmental processes. In the present survey, genes encoding proteins with conserved HMG-box, bZip domains, and some types of zinc finger motifs were surveyed in the completely sequenced genome of Ciona intestinalis. In the present analysis, 21 HMG-box-containing genes and 26 bZip genes were identified as well as four small groups of zinc finger genes in the Ciona genome. The results also showed that a less redundant set of genes is present in the Ciona genome compared with vertebrate genomes. In addition, cDNA clones for almost all genes identified have been cloned and distributed as a Ciona intestinalis Gene Collection Release I. The present comprehensive analysis therefore provides a means to study the role of these transcription factors in developmental processes of basal chordates.

Discrete element modelling of the influence of lifters on power draw of tumbling mills

Crushing and grinding are the most energy intensive part of the mineral recovery process. A major part of rock size reduction occurs in tumbling mills. Empirical models for the power draw of tumbling mills do not consider the effect of lifters. Discrete element modelling was used to investigate the effect of lifter condition on the power draw of tumbling mill. Results obtained with PFC3D code show that lifter condition will have a significant influence on the power draw and on the mode of energy consumption in the mill. Relatively high lifters will consume less power than low lifters, under otherwise identical conditions. The fraction of the power that will be consumed as friction will increase as the height of the lifters decreases. This will result in less power being used for high intensity comminution caused by the impacts. The fraction of the power that will be used to overcome frictional resistance is determined by the material's coefficient of friction. Based on the modelled results, it appears that the effective coefficient of friction for in situ mill is close to 0.1. (C) 2003 Elsevier Science Ltd. All rights reserved.

Applying discrete element modelling to vertical and horizontal shaft impact crushers

The PFC3D (particle flow code) that models the movement and interaction of particles by the DEM techniques was employed to simulate the particle movement and to calculate the velocity and energy distribution of collision in two types of impact crusher: the Canica vertical shaft crusher and the BJD horizontal shaft swing hammer mill. The distribution of collision energies was then converted into a product size distribution for a particular ore type using JKMRC impact breakage test data. Experimental data of the Canica VSI crusher treating quarry and the BJD hammer mill treating coal were used to verify the DEM simulation results. Upon the DEM procedures being validated, a detailed simulation study was conducted to investigate the effects of the machine design and operational conditions on velocity and energy distributions of collision inside the milling chamber and on the particle breakage behaviour. (C) 2003 Elsevier Ltd. All rights reserved.

Discrete element modelling of power draw of tumbling mills

The power required to operate large mills is typically 5-10 MW. Hence, optimisation of power consumption will have a significant impact on overall economic performance and environmental impact. Power draw modelling results using the discrete element code PFC3D have been compared with results derived from the widely used empirical Model of Morrell. This is achieved by calculating the power draw for a range of operating conditions for constant mill size and fill factor using two modelling approaches. fThe discrete element modelling results show that, apart from density, selection of the appropriate material damping ratio is critical for the accuracy of modelling of the mill power draw. The relative insensitivity of the power draw to the material stiffness allows selection of moderate stiffness values, which result in acceptable computation time. The results obtained confirm that modelling of the power draw for a vertical slice of the mill, of thickness 20% of the mill length, is a reliable substitute for modelling the full mill. The power draw predictions from PFC3D show good agreement with those obtained using the empirical model. Due to its inherent flexibility, power draw modelling using PFC3D appears to be a viable and attractive alternative to empirical models where necessary code and computer power are available.

Designing a 161-element Ku-band microstrip reflectarray of variable size patches using an equivalent unit cell waveguide approach

An equivalent unit cell waveguide approach (WGA) to designing 4 multilayer microstrip reflectarray of variable size patches is presented. In this approach, a normal incidence of a plane wave on an infinite periodic array of radiating elements is considered to obtain reflection coefficient phase curves for the reflectarray's elements. It is shown that this problem is equivalent to the problem of reflection of the dominant TEM mode in a waveguide with patches interleaved by layers of dielectric. This waveguide problem is solved using a field matching technique and a method of moments (MoM). Based on this solution, a fast computer algorithm is developed to generate reflection coefficient phase curves for a multilayer microstrip patch reflectarray. The validity of the developed algorithm is tested against alternative approaches and Agilent High Frequency Structure Simulator (HFSS). Having confirmed the validity of the WGA approach, a small offset feed two-layer microstrip patch array is designed and developed. This reflectarray is tested experimentally and shows good performance.

The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro

Sox8 is a member of the Sox family of developmental transcription factor genes and is closely related to Sox9, a key gene in the testis determination pathway in mammals. Like Sox9, Sox8 is expressed in the developing mouse testis around the time of sex determination, suggesting that it might play a role in regulating the expression of testis-specific genes. An early step in male sex differentiation is the expression of anti-Mullerian hormone (AMH) in Sertoli cells. Expression of the Amh gene during sex differentiation requires the interaction of several transcription factors, including SF1, SOX9, GATA4, WT1, and DAX1. Here we show that SOX8 may also be involved in regulating the expression of Amh. Expression of Sox8 begins just prior to that of Amh at 12 days post coitum (dpc) in mouse testes and continues beyond 16 dpc in Sertoli cells. In vitro assays showed that SOX8 binds specifically to SOX binding sites within the Amh minimal promoter and, like SOX9, acts synergistically with SF1 through direct protein-protein interaction to enhance Amh expression, albeit at lower levels compared with SOX9. SOX8 and SOX9 appear to have arisen from a common ancestral gene and may have retained some common functions during sexual development. Our data provide the first evidence that SOX8 may partially compensate for the reduced SOX9 activity in campomelic dysplasia and substitute for Sox9 where Sox9 is either not expressed or expressed too late to be involved in sex determination or regulation of Amh expression.

Geometric nonlinear analysis of thin plates by a refined nonlinear non-conforming triangular plate element

Based on the refined non-conforming element method for geometric nonlinear analysis, a refined nonlinear non-conforming triangular plate element is constructed using the Total Lagrangian (T.L.) and the Updated Lagrangian (U.L.) approach. The refined nonlinear non-conforming triangular plate element is based on the Allman's triangular plane element with drilling degrees of freedom [1] and the refined non-conforming triangular plate element RT9 [2]. The element is used to analyze the geometric nonlinear behavior of plates and the numerical examples show that the refined non-conforming triangular plate element by the T.L. and U.L. approach can give satisfactory results. The computed results obtained from the T.L. and U.L. approach for the same numerical examples are somewhat different and the reasons for the difference of the computed results are given in detail in this paper. © 2003 Elsevier Science Ltd. All rights reserved.

The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyltransferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARgamma/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

The application of wave induced forces to a two-dimensional finite element long wave hydrodynamic model

This paper describes the modification of a two-dimensional finite element long wave hydrodynamic model in order to predict the net current and water levels attributable to the influences of waves. Tests examine the effects of the application of wave induced forces, including comparisons to a physical experiment. An example of a real river system is presented with comparisons to measured data, which demonstrate the importance of simulating the combined effects of tides and waves upon hydrodynamic behavior. (C) 2002 Elsevier Science Ltd. All rights reserved.

The basal ganglia and semantic engagement: Potential insights from semantic priming in individuals with subcortical vascular lesions, Parkinson's disease, and cortical lesions

The impact of basal ganglia dysfunction on semantic processing was investigated by comparing the performance of individuals with nonthalamic subcortical (NS) vascular lesions, Parkinson's disease (PD), cortical lesions, and matched controls on a semantic priming task. Unequibiased lexical ambiguity primes were used in auditory prime-target pairs comprising 4 critical conditions; dominant related (e.g., bank-money), subordinate related (e.g., bank-river), dominant unrelated (e.g.,foot-money) and subordinate unrelated (e.g., bat-river). Participants made speeded lexical decisions (word/nonword) on targets using a go-no-go response. When a short prime-target interstimulus interval (ISI) of 200 ins was employed, all groups demonstrated priming for dominant and subordinate conditions, indicating nonselective meaning facilitation and intact automatic lexical processing. Differences emerged at the long ISI (1250 ms), where control and cortical lesion participants evidenced selective facilitation of the dominant meaning, whereas NS and PD groups demonstrated a protracted period of nonselective meaning facilitation. This finding suggests a circumscribed deficit in the selective attentional engagement of the semantic network on the basis of meaning frequency, possibly implicating a disturbance of frontal-subcortical systems influencing inhibitory semantic mechanisms.

Expressão da laminina na membrana basal em carcinoma escamocelular oral

A membrana basal é uma estrutura dinâmica que sofre modificações qualitativas e quantitativas durante a progressão do carcinoma escamocelular, e este processo é de fundamental importância na invasão neoplásica e metástase. OBJETIVO: O objetivo deste estudo foi investigar o comportamento da membrana basal em carcinomas escamocelulares de boca com diferentes graus de malignidade histológica através da expressão imuno-histoquímica da laminina. FORMA DE ESTUDO: Coorte histórica com corte transversal. MATERIAL E MÉTODO: Trinta e um casos de carcinoma escamocelular de boca foram submetidos à graduação histológica para tumores malignos. Através do método da streptavidina-biotina, foi verificada a expressão imuno-histoquímica da laminina em relação à sua intensidade e integridade nas lesões com diferentes graus de malignidade. RESULTADOS: Foram observadas diferenças estatisticamente significativas dos valores médios da intensidade e da continuidade de marcação da laminina em relação aos diferentes graus de malignidade. CONCLUSÃO: Ficou demonstrado que a laminina, uma glicoproteína presente na membrana basal, sofreu modificações diferenciadas em carcinomas escamocelulares de boca nos diferentes graus de malignidade histológica.

Estimating Local Part Thickness in Midplane Meshes for Finite Element Analysis

Within the development of motor vehicles, crash safety (e.g. occupant protection, pedestrian protection, low speed damageability), is one of the most important attributes. In order to be able to fulfill the increased requirements in the framework of shorter cycle times and rising pressure to reduce costs, car manufacturers keep intensifying the use of virtual development tools such as those in the domain of Computer Aided Engineering (CAE). For crash simulations, the explicit finite element method (FEM) is applied. The accuracy of the simulation process is highly dependent on the accuracy of the simulation model, including the midplane mesh. One of the roughest approximations typically made is the actual part thickness which, in reality, can vary locally. However, almost always a constant thickness value is defined throughout the entire part due to complexity reasons. On the other hand, for precise fracture analysis within FEM, the correct thickness consideration is one key enabler. Thus, availability of per element thickness information, which does not exist explicitly in the FEM model, can significantly contribute to an improved crash simulation quality, especially regarding fracture prediction. Even though the thickness is not explicitly available from the FEM model, it can be inferred from the original CAD geometric model through geometric calculations. This paper proposes and compares two thickness estimation algorithms based on ray tracing and nearest neighbour 3D range searches. A systematic quantitative analysis of the accuracy of both algorithms is presented, as well as a thorough identification of particular geometric arrangements under which their accuracy can be compared. These results enable the identification of each technique’s weaknesses and hint towards a new, integrated, approach to the problem that linearly combines the estimates produced by each algorithm.