Numerical and experimental study of a homogenizer impinging jet

High-pressure homogenization is a key unit operation used to disrupt cells containing intracellular bioproducts. Modeling and optimization of this unit are restrained by a lack of information on the flow conditions within a homogenizer value. A numerical investigation of the impinging radial jet within a homogenizer value is presented. Results for a laminar and turbulent (k-epsilon turbulent model) jet are obtained using the PHOENICS finite-volume code. Experimental measurement of the stagnation region width and correlation of the cell disruption efficiency with jet stagnation pressure both indicate that the impinging jet in the homogenizer system examined is likely to be laminar under normal operating conditions. Correlation of disruption data with laminar stagnation pressure provides a better description of experimental variability than existing correlations using total pressure drop or the grouping 1/Y(2)h(2).

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com

Gangliosides Are Important for the Preservation of the Structure and Organization of RBL-2H3 Mast Cells

Gangliosides are known to be important in many biological processes. However, details concerning the exact function of these glycosphingolipids in cell physiology are poorly understood. in this study, the role of gangliosides present on the surface of rodent mast cells in maintaining cell structure was examined using RBL-2H3 mast cells and two mutant cell lines (E5 and D1) deficient in the gangliosides, GM(1) and the alpha-galactosyl derivatives of the ganglioside GD(1b). The two deficient cell lines were morphologically different from each other as well as from the parental RBL-2H3 cells. Actin filaments in RBL-2H3 and E5 cells were under the plasma membrane following the spindle shape of the cells, whereas in D1 cells, they were concentrated in large membrane ruffles. Microtubules in RBL-2H3 and E5 cells radiated from the centrosome and were organized into long, straight bundles. The bundles in D1 cells were thicker and organized circumferentially under the plasma membrane. The endoplasmic reticulum, the Golgi complex, and the secretory granule matrix were also altered in the mutant cell lines. These results suggest that the mast cell-specific alpha-galactosyl derivatives of ganglioside GD(1b) and GM(1) are important in maintaining normal cell morphology. (J Histochern Cytochem 58:83-93, 2010)

Development and implementation of the population Fisher information matrix for the evaluation of population pharmacokinetic designs.

In population pharmacokinetic studies, the precision of parameter estimates is dependent on the population design. Methods based on the Fisher information matrix have been developed and extended to population studies to evaluate and optimize designs. In this paper we propose simple programming tools to evaluate population pharmacokinetic designs. This involved the development of an expression for the Fisher information matrix for nonlinear mixed-effects models, including estimation of the variance of the residual error. We implemented this expression as a generic function for two software applications: S-PLUS and MATLAB. The evaluation of population designs based on two pharmacokinetic examples from the literature is shown to illustrate the efficiency and the simplicity of this theoretic approach. Although no optimization method of the design is provided, these functions can be used to select and compare population designs among a large set of possible designs, avoiding a lot of simulations.

Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways

We show here that the neurotrophin nerve growth factor (NGF), which has been shown to be a mitogen for breast cancer cells, also stimulates cell survival through a distinct signaling pathway. Breast cancer cell lines (MCF-7, T47-D, BT-20, and MDA-MB-231) were found to express both types of NGF receptors: p140(trkA) and p75(NTR). The two other tyrosine kinase receptors for neurotrophins, TrkB and TrkC, were not expressed. The mitogenic effect of NGF on breast cancer cells required the tyrosine kinase activity of p140(trkA) as well as the mitogen-activated protein kinase (MAPK) cascade, but was independent of p75(NTR). I, contrast, the anti-apoptotic effect of NGF (studied using the ceramide analogue C2) required p75(NTR) as well as the activation of the transcription factor NF-kB, but neither p140(trkA) nor MAPK was necessary. Other neurotrophins (BDNF, NT-3, NT-4/5) also induced cell survival, although not proliferation, emphasizing the importance of p75(NTR) in NGF-mediated survival. Both the pharmacological NF-KB inhibitor SN50, and cell transfection with IkBm, resulted in a diminution of NGF anti-apoptotic effect. These data show that two distinct signaling pathways are required for NGF activity and confirm the roles played by p75(NTR) and NF-kappaB in the activation of the survival pathway in breast cancer cells.

Relationship of XIST expression and responses of ovarian cancer to chemotherapy

Expression profiling to characterize cancer pharmacology has become a new approach to discover novel molecular targets for prognostic markers and cancer therapy. In a study to compare the global RNA expression profiles between primary and recurrent ovarian tumors from the same patient, we have identified XIST (inactive X chromosome-specific transcripts) as the most differentially expressed gene that was down-regulated in the recurrent tumor. XIST encodes a spliced noncoding polyadenylated transcript that is unique in being expressed exclusively from the inactive X chromosome and is involved in the X-inactivation process. Subsequent characterization of XIST expression in a panel of female cancer cell lines showed that the expression level of XIST correlates significantly with Taxol sensitivity. The clinical relevance of this observation is demonstrated by the strong association between XIST RNA levels and disease-free periods of ovarian cancer patients in a group of 21 ovarian cancer cases with Taxol in the therapeutic regiments. Cytogenetic studies on ovarian cancer cell lines indicated that loss of inactive X chromosome is one mechanism for the loss of XIST transcripts in the cell lines. Our data suggest that XIST expression may be a potential marker for chemotherapeutic responses in ovarian cancer.

Phase equilibria and thermodynamics of zinc fuming slags

A range of materials is treated in zinc fuming processes to recover metal values and produce benign slag waste products. The selection of the optimum process conditions in these various technologies can be greatly assisted by the use of a chemical thermodynamic model of the system. In this paper the effects of slag chemistry on the liquidus temperatures, subliquidus phase equilibria and thermodynamic properties are described by the F*A*C*T computer package with the new thermodynamic database of the ZnO-PbO-FeO-Fe2O3-CaO-SiO2 system. The implications of these findings for plant practice are discussed.

Food safety and development of the beef industry in China

Food safety concerns have escalated in China as they have elsewhere, especially in relation to meats. Beef production and consumption has increased proportionately faster than all other meats over the last two decades. Yet the slaughtering, processing and marketing of beef remains, for the most part, extremely primitive when compared with Western beef supply chains. By comparing the economics of household slaughtering with that of various types of abattoirs, this paper explains why household slaughtering and wet markets still dominate beef processing and distribution in China. The negative economic, social and industry development implications of enforcing more stringent food safety regulations are highlighted. The willingness/capacity of consumers to pay the added cost of better inspection and other services to guarantee food safety is investigated. In this context, the paper also evaluates the market opportunities for both domestic and imported Green Beef. The paper questions the merit of policy initiatives aimed at modernising Chinese beef supply chains for the mass market along Western lines. (C) 2002 Elsevier Science Ltd. All rights reserved.

Ephrin-A5 induces rounding, blebbing and deadhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling

Eph receptor tyrosine kinases and ephrins regulate morphogenesis in the developing embryo where they effect adhesion and motility of interacting cells. Although scarcely expressed in adult tissues, Eph receptors and ephrins are overexpressed in a range of tumours. In malignant melanoma, increased Eph and ephrin expression levels correlate with metastatic progression. We have examined cellular and biochemical responses of EphA3-expressing melanoma cell lines and human epithelial kidney 293T cells to stimulation with polymeric ephrin-A5 in solution and with surfaces of defined ephrin-A5 densities. Within minutes, rapid reorganisation of the actin and myosin cytoskeleton occurs through activation of RhoA, leading to the retraction of cellular protrusions, membrane blebbing and detachment, but not apoptosis. These responses are inhibited by monomeric ephrin-A5, showing that receptor clustering is required for this EphA3 response. Furthermore, the adapter CrkII, which associates with tyrosine-phosphorylated EphA3 in vitro, is recruited in vivo to ephrin-A5-stimulated EphA3. Expression of an SH3-domain mutated CrkII ablates cell rounding, blebbing and detachment. Our results suggest that recruitment of CrkII and activation of Rho signalling are responsible for EphA3-mediated cell rounding, blebbing and de-adhesion, and that ephrin-A5-mediated receptor clustering and EphA3 tyrosine kinase activity are essential for this response.

Effect of sorghum resistant to Stenodiplosis sorghicola (Coquillett) (Diptera: Cecidomyiidae) on oviposition and development of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae)

Helicoverpa armigera oviposition preference for, and larval development on sorghum hybrids with differing resistance to sorghum midge, Stenodiplosis sorghicola, were investigated. When H. armigera larvae were fed seed of resistant and susceptible hybrids in the laboratory there were no differences in larval and pupal sizes or the rate of development. The same result was recorded when larvae fed on panicles on plants in a glasshouse. On some sampling occasions, significantly more eggs were laid on panicles of resistant hybrids in the field. This occurred when plants were in plots and also in a mixed planting. Midge-resistance status did not affect levels of egg parasitism. In a field study using recombinant inbred lines between a midge-resistant and a midge-susceptible line, no relationship was found between level of resistance and oviposition of H. armigera. We conclude that, although midge-resistant hybrids are sometimes preferred for oviposition by H. armigera, the resistance per se does not determine this preference. Egg survival, larval survival, development and resultant damage are not significantly affected by the midge-resistance status of the host.

Efficacy, timing and method of application of fungicides for management of sorghum ergot caused by Claviceps africana

Trials conducted in Queensland, Australia between 1997 and 2002 demonstrated that fungicides belonging to the triazole group were the most effective in minimising the severity of infection of sorghum by Claviceps africana, the causal agent of sorghum ergot. Triadimenol ( as Bayfidan 250EC) at 0.125 kg a. i./ha was the most effective fungicide. A combination of the systemic activated resistance compound acibenzolar-S-methyl ( as Bion 50WG) at 0.05 kg a. i./ha and mancozeb ( as Penncozeb 750DF) at 1.5 kg a. i./ha has the potential to provide protection against the pathogen, should triazole-resistant isolates be detected. Timing and method of fungicide application are important. Our results suggest that the triazole fungicides have no systemic activity in sorghum panicles, necessitating the need for multiple applications from first anthesis to the end of flowering, whereas acibenzolar-S-methyl is most effective when applied 4 days before flowering. The flat fan nozzles tested in the trials provided higher levels of protection against C. africana and greater droplet deposition on panicles than the tested hollow cone nozzles. Application of triadimenol by a fixed wing aircraft was as efficacious as application through a tractor-mounted boom spray.

A genetic algorithm/method of moments approach to the optimization of an RF coil for MRI applications - Theoretical considerations - Abstract

A Combined Genetic Algorithm and Method of Moments design methods is presented for the design of unusual near-field antennas for use in Magnetic Resonance Imaging systems. The method is successfully applied to the design of an asymmetric coil structure for use at 190MHz and demonstrates excellent radiofrequency field homogeneity.

Preparation and characterization of Nickel-and cobalt-doped magnetites

Trabalho apresentado no I Simpósio Mineiro de Ciências dos Materiais, Ouro Preto, Novembro de 2001.

An efficient method for optimal location and sizing of fixed and switched shunt capacitors in large distribution systems

This paper proposes a computationally efficient methodology for the optimal location and sizing of static and switched shunt capacitors in large distribution systems. The problem is formulated as the maximization of the savings produced by the reduction in energy losses and the avoided costs due to investment deferral in the expansion of the network. The proposed method selects the nodes to be compensated, as well as the optimal capacitor ratings and their operational characteristics, i.e. fixed or switched. After an appropriate linearization, the optimization problem was formulated as a large-scale mixed-integer linear problem, suitable for being solved by means of a widespread commercial package. Results of the proposed optimizing method are compared with another recent methodology reported in the literature using two test cases: a 15-bus and a 33-bus distribution network. For the both cases tested, the proposed methodology delivers better solutions indicated by higher loss savings, which are achieved with lower amounts of capacitive compensation. The proposed method has also been applied for compensating to an actual large distribution network served by AES-Venezuela in the metropolitan area of Caracas. A convergence time of about 4 seconds after 22298 iterations demonstrates the ability of the proposed methodology for efficiently handling large-scale compensation problems.