CFD simulation of complex phenomena containing suspensions and flow throughporous media

There is an increasing reliance on computers to solve complex engineering problems. This is because computers, in addition to supporting the development and implementation of adequate and clear models, can especially minimize the financial support required. The ability of computers to perform complex calculations at high speed has enabled the creation of highly complex systems to model real-world phenomena. The complexity of the fluid dynamics problem makes it difficult or impossible to solve equations of an object in a flow exactly. Approximate solutions can be obtained by construction and measurement of prototypes placed in a flow, or by use of a numerical simulation. Since usage of prototypes can be prohibitively time-consuming and expensive, many have turned to simulations to provide insight during the engineering process. In this case the simulation setup and parameters can be altered much more easily than one could with a real-world experiment. The objective of this research work is to develop numerical models for different suspensions (fiber suspensions, blood flow through microvessels and branching geometries, and magnetic fluids), and also fluid flow through porous media. The models will have merit as a scientific tool and will also have practical application in industries. Most of the numerical simulations were done by the commercial software, Fluent, and user defined functions were added to apply a multiscale method and magnetic field. The results from simulation of fiber suspension can elucidate the physics behind the break up of a fiber floc, opening the possibility for developing a meaningful numerical model of the fiber flow. The simulation of blood movement from an arteriole through a venule via a capillary showed that the model based on VOF can successfully predict the deformation and flow of RBCs in an arteriole. Furthermore, the result corresponds to the experimental observation illustrates that the RBC is deformed during the movement. The concluding remarks presented, provide a correct methodology and a mathematical and numerical framework for the simulation of blood flows in branching. Analysis of ferrofluids simulations indicate that the magnetic Soret effect can be even higher than the conventional one and its strength depends on the strength of magnetic field, confirmed experimentally by Völker and Odenbach. It was also shown that when a magnetic field is perpendicular to the temperature gradient, there will be additional increase in the heat transfer compared to the cases where the magnetic field is parallel to the temperature gradient. In addition, the statistical evaluation (Taguchi technique) on magnetic fluids showed that the temperature and initial concentration of the magnetic phase exert the maximum and minimum contribution to the thermodiffusion, respectively. In the simulation of flow through porous media, dimensionless pressure drop was studied at different Reynolds numbers, based on pore permeability and interstitial fluid velocity. The obtained results agreed well with the correlation of Macdonald et al. (1979) for the range of actual flow Reynolds studied. Furthermore, calculated results for the dispersion coefficients in the cylinder geometry were found to be in agreement with those of Seymour and Callaghan.

On the Connectivity of the Julia sets of meromorphic functions

We prove that every transcendental meromorphic map $f$ with disconnected Julia set has a weakly repelling fixed point. This implies that the Julia set of Newton's method for finding zeroes of an entire map is connected. Moreover, extending a result of Cowen for holomorphic self-maps of the disc, we show the existence of absorbing domains for holomorphic self-maps of hyperbolic regions, whose iterates tend to a boundary point. In particular, the results imply that periodic Baker domains of Newton's method for entire maps are simply connected, which solves a well-known open question.

Searching for novel gene functions in yeast : identification of thousands of novel molecular interactions by protein-fragment complementation assay followed by automated gene function prediction and high-throughput lipidomics

La compréhension de processus biologiques complexes requiert des approches expérimentales et informatiques sophistiquées. Les récents progrès dans le domaine des stratégies génomiques fonctionnelles mettent dorénavant à notre disposition de puissants outils de collecte de données sur l’interconnectivité des gènes, des protéines et des petites molécules, dans le but d’étudier les principes organisationnels de leurs réseaux cellulaires. L’intégration de ces connaissances au sein d’un cadre de référence en biologie systémique permettrait la prédiction de nouvelles fonctions de gènes qui demeurent non caractérisées à ce jour. Afin de réaliser de telles prédictions à l’échelle génomique chez la levure Saccharomyces cerevisiae, nous avons développé une stratégie innovatrice qui combine le criblage interactomique à haut débit des interactions protéines-protéines, la prédiction de la fonction des gènes in silico ainsi que la validation de ces prédictions avec la lipidomique à haut débit. D’abord, nous avons exécuté un dépistage à grande échelle des interactions protéines-protéines à l’aide de la complémentation de fragments protéiques. Cette méthode a permis de déceler des interactions in vivo entre les protéines exprimées par leurs promoteurs naturels. De plus, aucun biais lié aux interactions des membranes n’a pu être mis en évidence avec cette méthode, comparativement aux autres techniques existantes qui décèlent les interactions protéines-protéines. Conséquemment, nous avons découvert plusieurs nouvelles interactions et nous avons augmenté la couverture d’un interactome d’homéostasie lipidique dont la compréhension demeure encore incomplète à ce jour. Par la suite, nous avons appliqué un algorithme d’apprentissage afin d’identifier huit gènes non caractérisés ayant un rôle potentiel dans le métabolisme des lipides. Finalement, nous avons étudié si ces gènes et un groupe de régulateurs transcriptionnels distincts, non préalablement impliqués avec les lipides, avaient un rôle dans l’homéostasie des lipides. Dans ce but, nous avons analysé les lipidomes des délétions mutantes de gènes sélectionnés. Afin d’examiner une grande quantité de souches, nous avons développé une plateforme à haut débit pour le criblage lipidomique à contenu élevé des bibliothèques de levures mutantes. Cette plateforme consiste en la spectrométrie de masse à haute resolution Orbitrap et en un cadre de traitement des données dédié et supportant le phénotypage des lipides de centaines de mutations de Saccharomyces cerevisiae. Les méthodes expérimentales en lipidomiques ont confirmé les prédictions fonctionnelles en démontrant certaines différences au sein des phénotypes métaboliques lipidiques des délétions mutantes ayant une absence des gènes YBR141C et YJR015W, connus pour leur implication dans le métabolisme des lipides. Une altération du phénotype lipidique a également été observé pour une délétion mutante du facteur de transcription KAR4 qui n’avait pas été auparavant lié au métabolisme lipidique. Tous ces résultats démontrent qu’un processus qui intègre l’acquisition de nouvelles interactions moléculaires, la prédiction informatique des fonctions des gènes et une plateforme lipidomique innovatrice à haut débit , constitue un ajout important aux méthodologies existantes en biologie systémique. Les développements en méthodologies génomiques fonctionnelles et en technologies lipidomiques fournissent donc de nouveaux moyens pour étudier les réseaux biologiques des eucaryotes supérieurs, incluant les mammifères. Par conséquent, le stratégie présenté ici détient un potentiel d’application au sein d’organismes plus complexes.

Insertion of a hydroxido bridge into a diphenoxido dinuclear copper(II) complex: drastic change of the magnetic property from strong antiferromagnetic to ferromagnetic and enhancement in the catecholase activity

A diphenoxido-bridged dinuclear copper(II) complex, [Cu2L2(ClO4)(2)] (1), has been synthesized using a tridentate reduced Schiff base ligand, 2-[[2-(diethylamino)-ethylamino]methyl]phenol (HL). The addition of triethylamine to the methanolic solution of this complex produced a novel triple bridged (double phenoxido and single hydroxido) dinuclear copper(II) complex, [Cu2L2(OH)]ClO4 (2). Both complexes 1 and 2 were characterized by X-ray structural analyses, variable-temperature magnetic susceptibility measurements, and spectroscopic methods. In 1, the two phenoxido bridges are equatorial-equatorial and the species shows strong antiferromagnetic coupling with J = -615.6(6.1) cm(-1). The inclusion of the equatorial-equatorial hydroxido bridge in 2 changes the Cu center dot center dot center dot Cu distance from 3.018 angstrom (avg.) to 2.798 angstrom (avg.), the positions of the phenoxido bridges to axial-equatorial, and the magnetic coupling to ferromagnetic with J = 50.1(1.4) cm(-1). Using 3,5-di-tert-butylcatechol as the substrate, the catecholase activity of the complexes has been studied in a methanol solution; compound 2 shows higher catecholase activity (k(cat) = 233.4 h(-1)) than compound 1 (k(cat) = 93.6 h(-1)). Both complexes generate identical species in solution, and they are interconvertible simply by changing the pH of their solutions. The higher catecholase activity of 2 seems to be due to the presence of the OH group, which increases the pH of its solution.

Intelligence functions disorders in patients with complex partial epilepsy

Objective: To compare the performance of patients with complex partial epilepsy with the normal controls in the subtests of an instrument used to assess intelligence function. Method: Fifty epileptic patients, whose ages ranged from 19 to 49 years and 20 normal controls without any neuropsychiatric disorders. The Wechsler-Bellevue adult intelligence test was applied in groups, epileptic patients and control subjects. This test is composed of several subtests that assess specific cognitive functions. A statistical analysis was performed using non-parametric tests. Results: All the Wechsler-Bellevue subtests revealed that the intelligence functions of the patients were significantly inferior to that of the controls (p<0.05). This performance was supported by the patient's complaints in relation to their cognitive performance. Conclusion: Patients with complex partial epilepsy presented poorer results in the intelligence test when compared with individuals without neuropsychiatric disorders.

Liouville's theorem and power series for quaternionic functions

In recent years quaternionic functions have been an intense and prosperous object of research, and important results were determined [1]-[6]. Some of these results are similar to well known cases in one complex variable, op. cit. [5], [6]. In this paper the hypercomplex expansion of a function in a power series as well as determination of a Liouville's type theorem have been investigated to the quaternionic functions. In this case, it is observed that the Liouville's type theorem is true for second order derivatives, which differs from its classical version. © 2011 Academic Publications, Ltd.

Measurement of the muon charge asymmetry in inclusive pp -> W plus X production at root s=7 TeV and an improved determination of light parton distribution functions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Detection of bla(CTX-M)-type genes in complex class 1 integrons carried by Enterobacteriaceae isolated from retail chicken meat in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Application of reverse Monte Carlo simulations to diatomic molecules. Part 1. Noncomplete radial distribution functions

The reverse Monte Carlo (RMC) method generates sets of points in space which yield radial distribution functions (RDFS) that approximate those of the system of interest. Such sets of configurations should, in principle, be sufficient to determine the structural properties of the system. In this work we apply the RMC technique to fluids of hard diatomic molecules. The experimental RDFs of the hard-dimer fluid were generated by the conventional MC method and used as input in the RMC simulations. Our results indicate that the RMC method is only satisfactory in determining the local structure of the fluid studied by means of only mono-variable RDF. Also we suggest that the use of multi-variable RDFs would improve the technique significantly. However, the accuracy of the method turned out to be very sensitive to the variance of the input experimental RDF. © 1995.

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

Background: Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether NOTCH1 mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases. Methods: T-ALL subtypes, status of SIL-TAL1 fusion, ectopic expression of TLX3, and mutations in FBXW7, KRAS, PTEN and NOTCH1 were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test. Results: The frequencies of mutations were 43.5% for NOTCH1, while FBXW7, KRAS and PTEN exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of NOTCH1 mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between NOTCH1 mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. SIL-TAL1 was identified as an adverse prognostic factor. NOTCH1 mutation status was not associated with outcome, while the presence of NOTCH1 complex mutations (indels) were associated with a longer overall survival (p = 0.031) than point mutations. Conclusion: NOTCH1 mutations alone or in combination with FBXW7 did not impact T-ALL prognosis. Nevertheless, complex NOTCH1 mutations appear to have a positive impact on OS and the SIL-TAL1 fusion was validated as a negative prognostic marker in our series of T-ALL.

Systematics of the Oswaldoi Complex (Anopheles, Nyssorhynchus) in South America

Abstract Background Effective malaria control relies on accurate identification of those Anopheles mosquitoes responsible for the transmission of Plasmodium parasites. Anopheles oswaldoi s.l. has been incriminated as a malaria vector in Colombia and some localities in Brazil, but not ubiquitously throughout its Neotropical range. This evidence together with variable morphological characters and genetic differences supports that An. oswaldoi s.l. compromises a species complex. The recent fully integrated redescription of An. oswaldoi s.s. provides a solid taxonomic foundation from which to molecularly determine other members of the complex. Methods DNA sequences of the Second Internal Transcribed Spacer (ITS2 - rDNA) (n = 192) and the barcoding region of the Cytochrome Oxidase I gene (COI - mtDNA) (n = 110) were generated from 255 specimens of An. oswaldoi s.l. from 33 localities: Brazil (8 localities, including the lectotype series of An. oswaldoi), Ecuador (4), Colombia (17), Trinidad and Tobago (1), and Peru (3). COI sequences were analyzed employing the Kimura-two-parameter model (K2P), Bayesian analysis (MrBayes), Mixed Yule-Coalescent model (MYC, for delimitation of clusters) and TCS genealogies. Results Separate and combined analysis of the COI and ITS2 data sets unequivocally supported four separate species: two previously determined (An. oswaldoi s.s. and An. oswaldoi B) and two newly designated species in the Oswaldoi Complex (An. oswaldoi A and An. sp. nr. konderi). The COI intra- and inter-specific genetic distances for the four taxa were non-overlapping, averaging 0.012 (0.007 to 0.020) and 0.052 (0.038 to 0.064), respectively. The concurring four clusters delineated by MrBayes and MYC, and four independent TCS networks, strongly confirmed their separate species status. In addition, An. konderi of Sallum should be regarded as unique with respect to the above. Despite initially being included as an outgroup taxon, this species falls well within the examined taxa, suggesting a combined analysis of these taxa would be most appropriate. Conclusions: Through novel data and retrospective comparison of available COI and ITS2 DNA sequences, evidence is shown to support the separate species status of An. oswaldoi s.s., An. oswaldoi A and An. oswaldoi B, and at least two species in the closely related An. konderi complex (An. sp. nr. konderi, An. konderi of Sallum). Although An. oswaldoi s.s. has never been implicated in malaria transmission, An. oswaldoi B is a confirmed vector and the new species An. oswaldoi A and An. sp. nr. konderi are circumstantially implicated, most likely acting as secondary vectors.

Detection of complex point targets with distributed assets in a MIMO radar system

The report explores the problem of detecting complex point target models in a MIMO radar system. A complex point target is a mathematical and statistical model for a radar target that is not resolved in space, but exhibits varying complex reflectivity across the different bistatic view angles. The complex reflectivity can be modeled as a complex stochastic process whose index set is the set of all the bistatic view angles, and the parameters of the stochastic process follow from an analysis of a target model comprising a number of ideal point scatterers randomly located within some radius of the targets center of mass. The proposed complex point targets may be applicable to statistical inference in multistatic or MIMO radar system. Six different target models are summarized here – three 2-dimensional (Gaussian, Uniform Square, and Uniform Circle) and three 3-dimensional (Gaussian, Uniform Cube, and Uniform Sphere). They are assumed to have different distributions on the location of the point scatterers within the target. We develop data models for the received signals from such targets in the MIMO radar system with distributed assets and partially correlated signals, and consider the resulting detection problem which reduces to the familiar Gauss-Gauss detection problem. We illustrate that the target parameter and transmit signal have an influence on the detector performance through target extent and the SNR respectively. A series of the receiver operator characteristic (ROC) curves are generated to notice the impact on the detector for varying SNR. Kullback–Leibler (KL) divergence is applied to obtain the approximate mean difference between density functions the scatterers assume inside the target models to show the change in the performance of the detector with target extent of the point scatterers.

THE DOMAINS OF THE CATALYTIC SUBUNIT OF THE EUKARYOTIC RNA DEGRADING EXOSOME, RRP44P, HAVE DISTINCT FUNCTIONS

The exosome is a 3’ to 5’ exoribonuclease complex that consists of ten essential subunits. In the cytoplasm, the exosome degrades mRNA in a general mRNA turnover pathway and in several mRNA surveillance pathways. In the nucleus, the exosome processes RNA precursors to form small, stable, mature RNA species, including rRNA, snRNA, and snoRNA. In addition to processing these RNAs, the nuclear exosome is also involved in degrading aberrantly processed forms of these RNAs, and others, including mRNA. The 3’ to 5’ exoribonuclease activity of the exosome is contributed by the RNB domain of the only catalytically active subunit, Rrp44p, a member of the RNase II family of enzymes. In addition to the RNB domain, Rrp44p consists of three putative RNA binding domains and has an uncharacterized N-terminus, which includes a CR3 region and PIN domain. In an effort to characterize the cellular functions of the domains of Rrp44p, this study identified a second nuclease active site in the PIN domain. Specifically, the PIN domain exhibits endoribonuclease activity in vitro and is essential for exosome function. Further analysis of the nuclease activities of Rrp44p indicate a role for the exoribonuclease activity of Rrp44p in the cytoplasmic and nuclear exosome. This work has also characterized the CR3 region of Rrp44p, a region that has not yet been characterized in any other protein. This region is needed for the majority, if not all, of the cytoplasmic exosome functions as well as for interaction with the exosome. The CR3 region, along with a histidine residue in the N-terminus of Rrp44p, may coordinate a zinc atom. Preliminary evidence supports a role for this coordination in exosome function. Further investigation, however, is needed to determine the molecular dependence of the exosome on the CR3 region of Rrp44p. Despite its initial discovery thirteen years ago, the essential function of Rrp44p, and the exosome, is not yet known. The studies presented here, however, indicate that the essential function of Rrp44p and the exosome is in the nucleus and depends on the nuclease activities of Rrp44p.

Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo , while demonstrating anti-angiogenic activities

Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.

The regulation of mTORC2 kinase activity and complex integrity

Growth factor signaling promotes anabolic processes via activation of the PI3K-Akt kinase cascade. Deregulation of the growth factor-dependent PI3K-Akt pathway was implicated in tumorigenesis. Akt is an essential serine/threonine protein kinase that controls multiple physiological functions such as cell growth, proliferation, and survival to maintain cellular homeostasis. Recently, the mammalian Target of Rapamycin Complex 2 (mTORC2) was identified as the main Akt Ser-473 kinase, and Ser-473 phosphorylation is required for Akt hyperactivation. However, the detailed mechanism of mTORC2 regulation in response to growth factor stimulation or cellular stresses is not well understood. In the first project, we studied the regulation of the mTORC2-Akt signaling under ER stress. We identified the inactivation of mTORC2 by glycogen synthase kinase-3β (GSK-3β). Under ER stress, the essential mTORC2 component, rictor, is phosphorylated by GSK-3β at Ser-1235. This phosphorylation event results in the inhibition of mTORC2 kinase activity by interrupting Akt binding to mTORC2. Blocking rictor Ser-1235 phosphorylation can attenuate the negative impacts of GSK-3β on mTORC2/Akt signaling and tumor growth. Thus, our work demonstrated that GSK-3β-mediated rictor Ser-1235 phosphorylation in response to ER stress interferes with Akt signaling by inhibiting mTORC2 kinase activity. In the second project, I investigated the regulation of the mTORC2 integrity. We found that basal mTOR kinase activity depends on ATP level, which is tightly regulated by cell metabolism. The ATP-sensitive mTOR kinase is required for SIN1 protein phosphorylation and stabilization. SIN1 is an indispensable subunit of mTORC2 and is required for the complex assembly and mTORC2 kinase activity. Our findings reveal that mTOR-mediated phosphorylation of SIN1 is critical for maintaining complex integrity by preventing SIN1 from lysosomal degradation. In sum, our findings verify two distinct mTORC2 regulatory mechanisms via its components rictor and SIN1. First, GSK-3β-mediated rictor Ser-1235 phosphorylation results in mTORC2 inactivation by interfering its substrate binding ability. Second, mTOR-mediated Ser-260 phosphorylation of SIN1 preserves its complex integrity. Thus, these two projects provide novel insights into the regulation of mTORC2.