Bubble-to-Slug Transition for Low-Re Two-Phase Flows

A critical review on the mechanism and models on the bubble-to-slug transition of two-phase gas-liquid flows are presented in the present paper. It is shown that the most possible mechanism controlled the bubble-to-slug transition is the bubble coalescence. Focusing on the bubble-to-slug transition for the low-Re two-phase flow, a simple Monte Carlo method is used to simulate the influence of the initial bubble size on the bubble-to-slug transition. Some secondary factors, such as the liquid viscosity, the surface tension, and the relative slip between the two phases, are ignored in the present study. It is found that the locus of the dimensionless rate of collision is a universal curve. Based on this curve, it is determined that the bubble initial size can affect the phase distribution and flow pattern when its dimensionless value is in the range from 0.03 to 0.4. A simple relationship between the critical void fraction and the initial bubble size is proposed, which agrees very well with the experimental data.

Fine mapping and functional analysis of the multiple sclerosis risk gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. ��� CD4+ na����ve cells, P = 0.0001; CD8+ na����ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.

Increased opioid dependence in a mouse model of panic disorder

[EN] Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

353 p��gs.

Determinantal hypersurface from a geometric perspective

In this paper, we give a geometric interpretation of determinantal forms, both in the case of general matrices and symmetric matrices. We will prove irreducibility of the determinantal singular loci and state its dimension. We also provide detailed description of the singular locus for small dimensions.

Molecular genetics of the Drosophila eyes absent gene

<p>The Drosophila compound eye has provided a genetic approach to understanding the specification of cell fates during differentiation. The eye is made up of some 750 repeated units or ommatidia, arranged in a lattice. The cellular composition of each ommatidium is identical. The arrangement of the lattice and the specification of cell fates in each ommatidium are thought to occur in development through cellular interactions with the local environment. Many mutations have been studied that disrupt the proper patterning and cell fating in the eye. The eyes absent (eya) mutation, the subject of this thesis, was chosen because of its eyeless phenotype. In eya mutants, eye progenitor cells undergo programmed cell death before the onset of patterning has occurred. The molecular genetic analysis of the gene is presented.</p> <p>The eye arises from the larval eye-antennal imaginal disc. During the third larval instar, a wave of differentiation progresses across the disc, marked by a furrow. Anterior to the furrow, proliferating cells are found in apparent disarray. Posterior to the furrow, clusters of differentiating cells can be discerned, that correspond to the ommatidia of the adult eye. Analysis of an allelic series of eya mutants in comparison to wild type revealed the presence of a selection point: a wave of programmed cell death that normally precedes the furrow. In eya mutants, an excessive number of eye progenitor cells die at this selection point, suggesting the eya gene influences the distribution of cells between fates of death and differentiation.</p> <p>In addition to its role in the eye, the eya gene has an embryonic function. The eye function is autonomous to the eye progenitor cells. Molecular maps of the eye and embryonic phenotypes are different. Therefore, the function of eya in the eye can be treated independently of the embryonic function. Cloning of the gene reveals two cDNA's that are identical except for the use of an alternatively-spliced 5' exon. The predicted protein products differ only at the N-termini. Sequence analysis shows these two proteins to be the first of their kind to be isolated. Trangenic studies using the two cDNA's show that either gene product is able to rescue the eye phenotype of eya mutants.</p> <p>The eya gene exhibits interallelic complementation. This interaction is an example of an "allelic position effect": an interaction that depends on the relative position in the genome of the two alleles, which is thought to be mediated by chromosomal pairing. The interaction at eya is essentially identical to a phenomenon known as transvection, which is an allelic position effect that is sensitive to certain kinds of chromosomal rearrangements. A current model for the mechanism of transvection is the trans action of gene regulatory regions. The eya locus is particularly well suited for the study of transvection because the mutant phenotypes can be quantified by scoring the size of the eye.</p> <p>The molecular genetic analysis of eya provides a system for uncovering mechanisms underlying differentiation, developmentally regulated programmed cell death, and gene regulation.</p>

Negative regulators of a growth factor-mediated signaling pathway in the nematode Caenorhabditis elegans

<p>Vulval differentiation in C. elegans is mediated by an Epidermal growth factor (EGF)- EGF receptor (EGFR) signaling pathway. I have cloned unc-101, a negative regulator of vulval differentiation of the nematode C. elegans. unc-101 encodes a homolog of AP47, the medium chain of the trans-Golgi clathrin-associated protein complex. This identity was confirmed by cloning and comparing sequence of a C. elegans homolog of AP50, the medium chain of the plasma membrane clathrin-associated protein complex. I provided the first genetic evidence that the trans-Golgi clathrin-coated vesicles are involved in regulation of an EGF signaling pathway. Most of the unc-101 alleles are deletions or nonsense mutations, suggesting that these alleles severely reduce the unc-101 activity. A hybrid gene that contains parts of unc-101 and mouse AP4 7 rescued at least two phenotypes of unc-101 mutations, the Unc and the suppression of vulvaless phenotype of let-23(sy1) mutation. Therefore, the functions of AP47 are conserved between nematodes and mammals.</p> <p>unc-101 mutations can cause a greater than wild-type vulval differentiation in combination with certain mutations in sli-1, another negative regulator of the vulval induction pathway. A mutation in a new gene, rok-1, causes no defect by itself, but causes a greater than wild-type vulval differentiation in the presence of a sli-1 mutation. The unc-101; rok-1; sli-1 triple mutants display a greater extent of vulval differentiation than any double mutant combinations of unc-101, rok-1 and sli-1. Therefore, rok-1 locus defines another negative regulator of the vulval induction pathway.</p> <p>I analyzed a second gene encoding an AP47 homolog in C. elegans. This gene, CEAP47, encodes a protein 72% identical to both unc-101 and mammalian AP47. A hybrid gene containing parts of unc-101 and CEAP47 sequences can rescue phenotypes of unc-101 mutants, indicating that UNC- 101 and CEAP47 proteins can be redundant if expressed in the same set of cells.</p>

I edo adikzio baten anatomia

[EN] This paper is devoted to i, the Basque dative case marker. In part I, the paper aims at presenting a general approach the locus of syntactic variation within Universal Grammar (sections 1.1 to 1.3). After an excursus on the use of minorized languages in science (1.4), a discussion on parameters is provided. In (1.5), the notion of macroparameter from the 80���s is critically discussed mainly but not along the lines of Newmeyer (2005). The last section (1.6)supports to focus on microparameters, along the lines of Kayne (2000, 2005), as the right way to properly understand and explain variation. Part II provides an analysis of the main properties of Basque datives (sections 2.1 and 2.2). Sections 2.3 and 2.4 are devoted to the nature of Basque inflectional morpheme (k)i, interpreted asan applicative morpheme which ���applies��� dative object arguments to the structure. Finally, microcomparative analyses on Basque Differential Object Marking and Dative Displacement are presented in sections (2.6) and (2.7) respectively.

Earthquakes of the Nepal Himalaya : towards a physical model of the seismic cycle

Home to hundreds of millions of souls and land of excessiveness, the Himalaya is also the locus of a unique seismicity whose scope and peculiarities still remain to this day somewhat mysterious. Having claimed the lives of kings, or turned ancient timeworn cities into heaps of rubbles and ruins, earthquakes eerily inhabit Nepalese folk tales with the fatalistic message that nothing lasts forever. From a scientific point of view as much as from a human perspective, solving the mysteries of Himalayan seismicity thus represents a challenge of prime importance. Documenting geodetic strain across the Nepal Himalaya with various GPS and leveling data, we show that unlike other subduction zones that exhibit a heterogeneous and patchy coupling pattern along strike, the last hundred kilometers of the Main Himalayan Thrust fault, or MHT, appear to be uniformly locked, devoid of any of the ���creeping barriers��� that traditionally ward off the propagation of large events. The approximately 20 mm/yr of reckoned convergence across the Himalaya matching previously established estimates of the secular deformation at the front of the arc, the slip accumulated at depth has to somehow elastically propagate all the way to the surface at some point. And yet, neither large events from the past nor currently recorded microseismicity nearly compensate for the massive moment deficit that quietly builds up under the giant mountains. Along with this large unbalanced moment deficit, the uncommonly homogeneous coupling pattern on the MHT raises the question of whether or not the locked portion of the MHT can rupture all at once in a giant earthquake. Univocally answering this question appears contingent on the still elusive estimate of the magnitude of the largest possible earthquake in the Himalaya, and requires tight constraints on local fault properties. What makes the Himalaya enigmatic also makes it the potential source of an incredible wealth of information, and we exploit some of the oddities of Himalayan seismicity in an effort to improve the understanding of earthquake physics and cipher out the properties of the MHT. Thanks to the Himalaya, the Indo-Gangetic plain is deluged each year under a tremendous amount of water during the annual summer monsoon that collects and bears down on the Indian plate enough to pull it away from the Eurasian plate slightly, temporarily relieving a small portion of the stress mounting on the MHT. As the rainwater evaporates in the dry winter season, the plate rebounds and tension is increased back on the fault. Interestingly, the mild waggle of stress induced by the monsoon rains is about the same size as that from solid-Earth tides which gently tug at the planets solid layers, but whereas changes in earthquake frequency correspond with the annually occurring monsoon, there is no such correlation with Earth tides, which oscillate back-and-forth twice a day. We therefore investigate the general response of the creeping and seismogenic parts of MHT to periodic stresses in order to link these observations to physical parameters. First, the response of the creeping part of the MHT is analyzed with a simple spring-and-slider system bearing rate-strengthening rheology, and we show that at the transition with the locked zone, where the friction becomes near velocity neutral, the response of the slip rate may be amplified at some periods, which values are analytically related to the physical parameters of the problem. Such predictions therefore hold the potential of constraining fault properties on the MHT, but still await observational counterparts to be applied, as nothing indicates that the variations of seismicity rate on the locked part of the MHT are the direct expressions of variations of the slip rate on its creeping part, and no variations of the slip rate have been singled out from the GPS measurements to this day. When shifting to the locked seismogenic part of the MHT, spring-and-slider models with rate-weakening rheology are insufficient to explain the contrasted responses of the seismicity to the periodic loads that tides and monsoon both place on the MHT. Instead, we resort to numerical simulations using the Boundary Integral CYCLes of Earthquakes algorithm and examine the response of a 2D finite fault embedded with a rate-weakening patch to harmonic stress perturbations of various periods. We show that such simulations are able to reproduce results consistent with a gradual amplification of sensitivity as the perturbing period get larger, up to a critical period corresponding to the characteristic time of evolution of the seismicity in response to a step-like perturbation of stress. This increase of sensitivity was not reproduced by simple 1D-spring-slider systems, probably because of the complexity of the nucleation process, reproduced only by 2D-fault models. When the nucleation zone is close to its critical unstable size, its growth becomes highly sensitive to any external perturbations and the timings of produced events may therefore find themselves highly affected. A fully analytical framework has yet to be developed and further work is needed to fully describe the behavior of the fault in terms of physical parameters, which will likely provide the keys to deduce constitutive properties of the MHT from seismological observations.

Ordinary mod p representations of the metaplectic cover of p-adic SL_2

We classify the genuine ordinary mod p representations of the metaplectic group SL(2,F)-tilde, where F is a p-adic field, and compute its genuine mod p spherical and Iwahori Hecke algebras. The motivation is an interest in a possible correspondence between genuine mod p representations of SL(2,F)-tilde and mod p representations of the dual group PGL(2,F), so we also compare the two Hecke algebras to the mod p spherical and Iwahori Hecke algebras of PGL(2,F). We show that the genuine mod p spherical Hecke algebra of SL(2,F)-tilde is isomorphic to the mod p spherical Hecke algebra of PGL(2,F), and that one can choose an isomorphism which is compatible with a natural, though partial, correspondence of unramified ordinary representations via the Hecke action on their spherical vectors. We then show that the genuine mod p Iwahori Hecke algebra of SL(2,F)-tilde is a subquotient of the mod p Iwahori Hecke algebra of PGL(2,F), but that the two algebras are not isomorphic. This is in contrast to the situation in characteristic 0, where by work of Savin one can recover the local Shimura correspondence for representations generated by their Iwahori fixed vectors from an isomorphism of Iwahori Hecke algebras.

Neuronal mechanism of state control in Drosophila melanogaster

<p>The changes in internal states, such as fear, hunger and sleep affect behavioral responses in animals. In most of the cases, these state-dependent influences are ���pleiotropic���: one state affects multiple sensory modalities and behaviors; ���scalable���: the strengths and choices of such modulations differ depending on the imminence of demands; and ���persistent���: once the state is switched on the effects last even after the internal demands are off. These prominent features of state-control enable animals to adjust their behavioral responses depending on their internal demands. Here, we studied the neuronal mechanisms of state-controls by investigating energy-deprived state (hunger state) and social-deprived state of fruit flies, Drosophila melanogaster, as prototypic models. To approach these questions, we developed two novel methods: a genetically based method to map sites of neuromodulation in the brain and optogenetic tools in Drosophila.</p> <p>These methods, and genetic perturbations, reveal that the effect of hunger to alter behavioral sensitivity to gustatory cues is mediate by two distinct neuromodulatory pathways. The neuropeptide F (NPF) ��� dopamine (DA) pathway increases sugar sensitivity under mild starvation, while the adipokinetic hormone (AKH)- short neuropeptide F (sNPF) pathway decreases bitter sensitivity under severe starvation. These two pathways are recruited under different levels of energy demands without any cross interaction. Effects of both of the pathways are mediated by modulation of the gustatory sensory neurons, which reinforce the concept that sensory neurons constitute an important locus for state-dependent control of behaviors. Our data suggests that multiple independent neuromodulatory pathways are underlying pleiotropic and scalable effects of the hunger state.</p> <p>In addition, using optogenetic tool, we show that the neural control of male courtship song can be separated into probabilistic/biasing, and deterministic/command-like components. The former, but not the latter, neurons are subject to functional modulation by social experience, supporting the idea that they constitute a locus of state-dependent influence. Interestingly, moreover, brief activation of the former, but not the latter, neurons trigger persistent behavioral response for more than 10 min. Altogether, these findings and new tools described in this dissertation offer new entry points for future researchers to understand the neuronal mechanism of state control.</p>

The tensile fracture of mild steel

<p>The fibrous and cleavage tensile fracture of an annealed mild steel was investigated. Round tensile specimens of two geometries, one straight and one with a circumferential notch, were pulled at temperatures between room temperature and liquid nitrogen temperature. Tensile fractures occurred at average strains from 0.02 to 0.87. The mechanism of fibrous fracture at room temperature was investigated metallographically. The stress-strain values at which fibrous and cleavage fractures are initiated were determined.</p> <p>Many fine microcracks, which are associated with pearlite colonies and inclusion stringers, develop prior to fibrous fracture. The macrofracture, which leads to final separation of the tensile specimen, is initiated by the propagation of a microcrack beyond the microstructural feature with which it is associated. Thus, the fibrous fracture of mild steel does not develop by the gradual growth and coalescence of voids that are large enough to be visible in the optical microscope. When the microcracks begin to open and propagate, final fracture quickly follows. Axial cracks are a prominent feature of the macrofracture that forms in the interior of the specimen immediately before final fracture.</p> <p>The Bridgman distribution of stresses is not valid in a notched tensile specimen. Fibrous and cleavage fractures occur at approximately the same value of maximum tensile stress. When the maximum tensile stress that is necessary for cleavage fracture is plotted against the corresponding maximum tensile strain, the result is an unique locus.</p>

Carga de trabalho de enfermeiros: uma an��lise do Nursing Activities Score (NAS)

Este estudo tem como objeto a carga de trabalho de enfermeiros que trabalham em unidades de cuidados semi-intensivos. Seu objetivo geral foi identificar e analisar a percep����o dos enfermeiros de uma unidade semi-intensiva acerca do instrumento Nursing Activities Score - NAS, tendo como foco o conceito de carga de trabalho. Os objetivos espec��ficos foram: identificar dom��nios do NAS considerados pelos enfermeiros como capazes de avaliar a carga de trabalho; identificar os itens que os enfermeiros consideram relevantes e manteriam no instrumento, os itens que excluiriam e os que acrescentariam; identificar itens que os enfermeiros consideram subdimensionados, para os quais aumentariam a pontua����o, os superdimensionados, para os quais diminuiriam a pontua����o; e, ao final, discutir implica����es dessa avalia����o para a organiza����o do trabalho e seus impactos na sa��de do trabalhador de enfermagem. Estudo de abordagem quantitativa do tipo descritivo explorat��ria, com breve aporte qualitativo, utilizando a triangula����o metodol��gica. O local de estudo foi uma unidade de m��dia complexidade com 35 leitos em um hospital privado do Rio de Janeiro. Participaram do estudo 28 enfermeiros e os dados foram coletados por meio de um question��rio com perguntas fechadas e abertas no per��odo de abril a maio de 2008. O tratamento dos dados foi realizado com apoio do software Excel, utilizando estat��stica descritiva. O material qualitativo foi organizado em categorias, usando elementos da An��lise de Conte��do Tem��tica. Entre os dom��nios, verificou-se que os enfermeiros consideram o que mais avalia a carga real de trabalho o Suporte Ventilat��rio, com 89%, e o dom��nio que n��o avalia a carga de trabalho foi o Suporte Neurol��gico, com 25%. Os tr��s dom��nios mais citados para serem acrescidos de atividades foram o Suporte Renal, com 25%, seguido Interven����o Especificas, com 21%, e Suporte Metab��lico, respectivamente. Quanto �� exclus��o de atividades, s�� dois dom��nios foram mencionados: Suporte Ventilat��rio, com 25%, e Atividade B��sica, com 21%. Os enfermeiros acham que 69% da pontua����o era adequada aos itens e 31% acreditam n��o estar adequada. No grupo, 27% aumentariam a pontua����o em alguns itens e 4% diminuiriam a pontua����o. Sobre a mensura����o da carga de trabalho, acreditam que essa colabora no processo de trabalho, 79%, e 57% acham que mensurar a carga de trabalho atrav��s do NAS pode auxiliar na preserva����o de sua sa��de. Conclu��mos que esse instrumento mensura a carga de trabalho na opini��o dos enfermeiros, mas precisa ser adaptado �� realidade da unidade onde est�� sendo aplicada. Al��m disso, os enfermeiros alteraram mais os itens relacionados �� carga f��sica sem identificar a carga ps��quica de trabalho como relevante, evidenciando que o trabalho de enfermagem precisa ser mais bem conhecido pelos enfermeiros no que se refere ��s dimens��es de impacto na sua sa��de.

Molecular genetic studies on voltage-gated ion channels

<p>Several different methods have been employed in the study of voltage-gated ion channels. Electrophysiological studies on excitable cells in vertebrates and molluscs have shown that many different voltage-gated potassium (K⁺) channels and sodium channels may coexist in the same organism. Parallel genetic studies in Drosophila have identified mutations in several genes that alter the properties of specific subsets of physiologically identified ion channels. Chapter 2 describes molecular studies that identify two Drosophila homologs of vertebrate sodium-channel genes. Mutations in one of these Drosophila sodium-channel genes are shown to be responsible for the temperature-dependent paralysis of a behavioural mutant para^ts. Evolutionary arguments, based on the partial sequences of the two Drosophila genes, suggest that subfamilies of voltage-gated sodium channels in vertebrates remain to be identified.</p> <p>In Drosophila, diverse voltage-gated K⁺ channels arise from alternatively spliced mRNAs generated at the Shaker locus. Chapter 3 and the Appendices describe the isolation and characterization of several human K⁺-channel genes, similar in sequence to Shaker. Each of these human genes has a highly conserved homolog in rodents; thus, this K⁺-channel gene family probably diversified prior to the mammalian radiation. Functional K⁺ channels encoded by these genes have been expressed in Xenopus oocytes and their properties have been analyzed by electrophysiological methods. These studies demonstrate that both transient and noninactivating voltage-gated K⁺ channels may be encoded by mammalian genes closely related to Shaker. In addition, results presented in Appendix 3 clearly demonstrate that independent gene products from two K⁺-channel genes may efficiently co-assemble into heterooligomeric K⁺ channels with properties distinct from either homomultimeric channel. This finding suggests yet another molecular mechanism for the generation of K⁺-channel diversity.</p>

Special Frobenius Traces in Galois Representations

<p>This thesis studies Frobenius traces in Galois representations from two different directions. In the first problem we explore how often they vanish in Artin-type representations. We give an upper bound for the density of the set of vanishing Frobenius traces in terms of the multiplicities of the irreducible components of the adjoint representation. Towards that, we construct an infinite family of representations of finite groups with an irreducible adjoint action.</p> <p>In the second problem we partially extend for Hilbert modular forms a result of Coleman and Edixhoven that the Hecke eigenvalues a_p of classical elliptical modular newforms f of weight 2 are never extremal, i.e., a_p is strictly less than 2[square root]p. The generalization currently applies only to prime ideals p of degree one, though we expect it to hold for p of any odd degree. However, an even degree prime can be extremal for f. We prove our result in each of the following instances: when one can move to a Shimura curve defined by a quaternion algebra, when f is a CM form, when the crystalline Frobenius is semi-simple, and when the strong Tate conjecture holds for a product of two Hilbert modular surfaces (or quaternionic Shimura surfaces) over a finite field.</p>