Ion source with corner cathode

An ion source may include first, second, and third electrodes. The first electrode may be a repeller having a V-shaped groove. The second electrode may be an electron emitter filament disposed adjacent the base of the V-shaped groove. The third electrode may be an anode that defines an enclosed volume with an aperture formed therein adjacent the electron emitter filament. A potential of the first electrode may be less than a potential of the second electrode, and the potential of the second electrode may be less than a potential of the third electrode. A fourth electrode that is disposed between the electron emitter filament and the anode may be used to produce a more collimated electron beam

Large eddy simulation tool for environmental and industrial processes

2007/2008Computational Fluid Dynamics (CFD) is an established tool for consulting and for basic research in fluid mechanics. CFD is required to provide information where analytical approaches or experiments would be impossible or too expensive. Most of the flows of engineering interest are turbulent. Turbulence is an unresolved problem of classical physics, because of the non linearity of the fluid motion equations. At the moment the only way to face them is numerically. Turbulence is composed of eddies in a broad range of size. To solve numerically the Navier-Stokes equations, the equations set that governs the fluid motion, a very fine grid is necessary in order to catch also the smallest eddies. The computational cost increases as Re3 (Re = ul/ is the Reynolds number with u and l an inertial velocity and length scales and the kinematic viscosity). Real life problems are characterized by very large Reynolds numbers and the consequent computational cost is enormous. So the direct solutions of Navier-Stokes equations (DNS) is not feasible. In many applications it is not necessary to solve all the eddies, it can be sufficient to supply the effects of unresolved scale to the flow. In Large Eddy Simulation (LES) most of the scales of motion are directly solved, in particular all the large energy carrying scales. These scales are influenced by the boundaries and they are strongly anisotropic. The smaller and dissipative scales must be modeled, but these scales loosing memory of the boundary conditions are more isotropic and hence formulating a general model that accounts for their effect is relatively easier. Large Eddy Simulation is a prospective tool for investigation in real life problems, in particular when high detailed analysis is required. This is the case for many industrial and environmental processes. For example, acoustic problems due to hydrodynamic noise are governed over a range of large scales which are easily reproduced by LES solution. However in these types of flows many difficulties arise also for LES. In general these flows are characterized by high Reynolds number. Wall-bounded flow at high Re requires high computational cost because LES is constrained to be DNS-like. Besides complex geometries are often involved. Structured or Unstructured body-fitted grid can be very hard to made, moreover unstructured grid can be expensive and not suited for LES. Scope of this thesis is to develop tools to apply LES to such configurations in order to make numerical simulation more adaptable to real life problems. In particular to deal with complex geometry an Immersed Boundary Methodology has been developed for curvilinear coordinates. The method has been applied to several test cases with good results. Then this methodology has been extended to high Reynolds number flows through the use of a wall model. In order to work on anisotropic grid, typical in sea coastal domain, a modified Smagorisky model has been proposed. Finally particle dispersion has been considered in stratified environmental flow. These tools has been applied to an industrial and to an environmental problem with good results.La fluidodinamica computazionale (CFD) ´e uno strumento affermato per le consulenze e per la ricerca di base nella meccanica dei fluidi. Alla CFD ´e richiesto di fornire informazioni quando approcci analitici o sperimentali sarebbero impossibili o troppo costosi. La maggior parte dei flussi di interesse ingegneristico ´e di tipo turbolento. La turbolenza ´e uno dei problemi irrisolti della fisica classica, ci´o ´e dovuto alla non linearit´a delle equazioni che governano il moto dei fluidi. Al momento l’unico modo per affrontarle ´e numericamente. La turbolenza si compone di vortici di diverse dimensioni. Per risolvere numericamente le equazioni di Navier-Stokes, le equazioni che governano il moto dei fluidi, una griglia molto fine ´e necessaria al fine di simulare propriamente anche i vortici di scala pi´u piccola. Il costo computazionale cresce come Re3 (Re = ul/ ´e il numero di Reynolds, con u e l una velocit´a ed una lunghezza scala caratteristici e la viscosit´a cinematica). I problemi reali sono caratterizzati da numeri di Reynolds altissimi e conseguentemente il costo computazionale di queste simulazioni ´e enorme. Per questo motivo la soluzione diretta delle equazioni di Navier-Stokes (DNS) non ´e possibile. In molte applicazioni non ´e necessario risolvere tutte le scale dei vortici, pu´o essere sufficiente fornire l’effetto delle scale non risolte al flusso. Nella Large Eddy Simulation gran parte delle scale di vortici ´e direttamente risolta, in particolare le larghe scale energetiche. Queste scale sono influenzate dalle condizioni al contorno e sono fortemente anisotrope. Le scale piccole e dissipative devono essere modellate, ma queste scale perdendo memoria delle condizioni al contorno sono generalmente isotrope ed un modello per riprodurre il loro effetto risulta semplice. La LES ´e uno strumento d’avanguardia per lo studio di flussi realistici, in particolare risulta molto potente quando vengono richieste analisi dettagliate del moto. Questo ´e il caso di molti problemi in campo industriale ed ambientale. Per esempio problemi acustici dovuti a rumore idrodinamico sono governati dalle grandi scale che nella LES sono facilmente riprodotte. Comunque anche per la LES sorgono molte difficolt´a nel affrontare questi problemi. Generalmente questi flussi sono caratterizzati da alti numeri di Reynolds. Flussi di parete ad alti Re richiedono un costo computazionale elevatissimo e alla fine la LES deve soddisfare a requisiti tipici della DNS. Inoltre spesso questi flussi sono caratterizzati da geometrie complesse. Griglie strutturate o non strutturate che si adattano alle geometrie possono essere molto difficili da sviluppare, inoltre le griglie non strutturate possono essere molto costose e non particolarmente adatte alla LES. Lo scopo di questa tesi ´e di sviluppare degli strumenti atti a rendere efficiente l’applicazione della LES a flussi realistici. In particolare per affrontare le geometrie complesse ´e stata sviluppata una metodologia Immersed Boundary per coordinate curvilinee. Il metodo ´e stato provato su diversi casi con buoni risultati. La metodologia ´e stata quindi estesa al caso di flussi ad alto numero di Reynolds tramite lo sviluppo di un modello parete. ´E stato quindi sviluppato un modello modificato di Smagorinsky per lavorare con griglie fortemente anisotrope, tipiche per flussi in ambito marino costiero. Infine ´e stata studiata la dispersione di particelle in flussi ambientali stratificati. Gli strumenti sviluppati sono stati quindi applicati ad un problema industriale ed ad uno ambientale con ottimi risultati.XXI Ciclo197

Mixing in lock-release gravity currents propagating up a slope

Lock-exchange gravity currents propagating up a slope are investigated by large eddy simulations, focusing on the entrainment and mixing processes occurring between the dense current and the ambient fluid. Relevant parameters, such as the aspect ratio of the initial volume of dense fluid in the lock R, the angle between the bottom boundary and the horizontal direction \u3b8 and the depth aspect ratio \u3c6, are varied. The numerical results are compared with laboratory experiments and a good agreement is found. Entrainment and mixing in a lock-release gravity current are studied using different entrainment parameters and an energy budget method. The entrainment is found to depend on both Froude, Fr, and Reynolds, Re, numbers. In addition, the dependence of both entrainment and mixing on the parameters varied is discussed. The entrainment decreases with increasing steepness of the bottom and R. Irreversible mixing is not affected by the varied parameters during the slumping phase, while during the successive phases of motion, it is found to decrease with the increase of \u3b8 and R. Low entrainment and mixing occur for \u3c6 <

Dynamics of long-term colonization of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains

The persistence and variability of 188 Haemophilus influenzae isolates in respiratory tract of 30 cystic fibrosis (CF) patients over the course of 7 years was studied. Antibiotic susceptibility testing, DNA fingerprinting, and analysis of outer membrane protein profiles were performed on all isolates. A total of 115 distinct pulsed-field gel electrophoresis profiles were identified. Ninety percent of patients were cocolonized with two or more clones over the studied period. A third of the patients were cross-colonized with one or two H. influenzae strains; 11% of the clones persisted for 3 or more months. Biotype, outer membrane protein profiles, and resistance profiles showed variation along the studied period, even in persisting clones. Four isolates (2.1%) recovered from 3 patients were type f capsulate, with three of them belonging to the same clone. beta-Lactamase production was detected in 23.9% of isolates while 7% of the beta-lactamase-negative isolates presented diminished susceptibility to ampicillin (beta-lactamase-negative ampicillin resistance phenotype). Remarkably, 21.3% of the H. influenzae isolates presented decreased susceptibility to ciprofloxacin, which was mainly observed in persisting clones. Of the H. influenzae isolates from CF patients, 18 (14.5%) were found to be hypermutable in comparison with 1 (1.4%) from non-CF patients (P < 0.0001). Ten patients (33.3%) were colonized by hypermutable strains over the study period. A multiresistance phenotype and long-term clonal persistence were significantly associated in some cases for up to 7 years. These results suggest that H. influenzae bronchial colonization in CF patients is a dynamic process, but better-adapted clones can persist for long periods of time.This work was supported by a research grant from the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Madrid, Spain (95-98/0364). We are grateful to E. Moguel for his technical assistance and to C. García (Hospital Lozano Blesa, Zaragoza) and J. C. Alados (Hospital Virgen de las Nieves, Granada) for their cooperation

Utility of Plasma Protein Biomarkers and Mid-Infrared Spectroscopy for Diagnosing Fracture-Related Infections: A Pilot Study.

OBJECTIVES: To compare a large panel of plasma protein inflammatory biomarkers and mid-infrared (MIR) spectral patterns between patients with confirmed fracture related infections (FRIs) and controls without infection. DESIGN: Prospective case-control. SETTING: Academic, level 1 trauma center. PATIENTS: Thirteen patients meeting confirmatory FRI criteria were matched to 13 controls based on age, time after surgery, and fracture region. INTERVENTION: Plasma levels of 49 proteins were measured using enzyme-linked immunosorbent assay (ELISA) techniques. Fourier transform infrared (FTIR) spectroscopy of dried films was used to obtain MIR spectra of plasma samples. MAIN OUTCOME MEASUREMENTS: Plasma protein levels and MIR spectra of samples. RESULTS: Multivariate analysis-based predictive model developed utilizing ELISA-based biomarkers had sensitivity, specificity, and accuracy of 69.2±0.0%, 99.9±1.0%, and 84.5±0.6%, respectively, with PDGF-AB/BB, CRP, and MIG selected as the minimum number of variables explaining group differences (P CONCLUSIONS: This pilot study demonstrates the feasibility of using a select panel of plasma proteins and FTIR spectroscopy to diagnose FRI. The preliminary data suggest that measurement of these select proteins and MIR spectra may be potential clinical tools to detect FRI. Further investigation of these biomarkers in a larger cohort of patients is warranted. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence

Axisymmetric three-dimensional gravity currents generated by lock exchange

Unconfined three-dimensional gravity currents generated by lock exchange using a small dividing gate in a sufficiently large tank are investigated by means of large eddy simulations under the Boussinesq approximation, with Grashof numbers varying over five orders of magnitudes. The study shows that, after an initial transient, the flow can be separated into an axisymmetric expansion and a globally translating motion. In particular, the circular frontline spreads like a constant-flow-rate, axially symmetric gravity current about a virtual source translating along the symmetry axis. The flow is characterised by the presence of lobe and cleft instabilities and hydrodynamic shocks. Depending on the Grashof number, the shocks can either be isolated or produced continuously. In the latter case a typical ring structure is visible in the density and velocity fields. The analysis of the frontal spreading of the axisymmetric part of the current indicates the presence of three regimes, namely, a slumping phase, an inertial-buoyancy equilibrium regime and a viscous-buoyancy equilibrium regime. The viscous-buoyancy phase is in good agreement with the model of Huppert (J. Fluid Mech., vol. 121, 1982, pp. 43-58), while the inertial phase is consistent with the experiments of Britter (Atmos. Environ., vol. 13, 1979, pp. 1241-1247), conducted for purely axially symmetric, constant inflow, gravity currents. The adoption of the slumping model of Huppert & Simpson (J. Fluid Mech., vol. 99 (04), 1980, pp. 785-799), which is here extended to the case of constant-flow-rate cylindrical currents, allows reconciling of the different theories about the initial radial spreading in the context of different asymptotic regimes. As expected, the slumping phase is governed by the Froude number at the lock's gate, whereas the transition to the viscous phase depends on both the Froude number at the gate and the Grashof number. The identification of the inertial-buoyancy regime in the presence of hydrodynamic shocks for this class of flows is important, due to the lack of analytical solutions for the similarity problem in the framework of shallow water theory. This fact has considerably slowed the research on variable-flow-rate axisymmetric gravity currents, as opposed to the rapid development of the knowledge about cylindrical constant-volume and planar gravity currents, despite their own environmental relevance

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD

The role of mutated SOD1 gene in synaptic stripping and MHC class I expression following nerve axotomy in ALS murine model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motoneuron death. Several cellular pathways have been described to be involved in ALS pathogenesis; however, the involvement of presynaptic stripping and the related MHC class I molecules in mutant SOD1 motoneurons remains to be clarified. To this purpose, we here investigated, for the first time, the motoneurons behavior, di per seand after facial axonal injury, in terms of synaptic stripping and MHC class I expression in wild-type (Wt) mice and in a murine model of ALS, the SOD1(G93A) mice, at the presymptomatic and symptomatic stage of the disease. Concerning Wt animals, we found a reduction in synaptophysin immunoreactivity and an increase of MHC class I molecules in facial motoneurons after axotomy. In uninjured motoneurons of SOD1(G93A) mice, an altered presynaptic framework was evident, and this phenomenon increased during the disease course. The alteration in the presynaptic input is related to excitatory fibers. Moreover, after injury, a further decrease of excitatory input was not associated to an upregulation of MHC class I molecules in motoneuron soma. This study demonstrates, for the first time, that the presence of mutated SOD1 protein affects the MHC class I molecules expression, altering the presynaptic input in motoneurons. Nevertheless, a positive MHC class I immunolabeling was evident in glial cells around facial injured motoneurons, underlying an involvement of these cells in synaptic stripping. This study contributes to better understand the involvement of the mutated SOD1 protein in the vulnerability of motoneurons after damage

Vacuolar H+-Pyrophosphatase AVP1 is Involved in Amine Fungicide Tolerance in Arabidopsis thaliana and Provides Tridemorph Resistance in Yeast

Amine fungicides are widely used as crop protectants. Their success is believed to be related to their ability to inhibit postlanosterol sterol biosynthesis in fungi, in particular sterol-Δ8,Δ7-isomerases and sterol-Δ14-reductases, with a concomitant accumulation of toxic abnormal sterols. However, their actual cellular effects and mechanisms of death induction are still poorly understood. Paradoxically, plants exhibit a natural resistance to amine fungicides although they have similar enzymes in postcicloartenol sterol biosynthesis that are also susceptible to fungicide inhibition. A major difference in vacuolar ion homeostasis between plants and fungi is the presence of a dual set of primary proton pumps in the former (V-ATPase and H+-pyrophosphatase), but only the V-ATPase in the latter. Abnormal sterols affect the proton-pumping capacity of V-ATPases in fungi and this has been proposed as a major determinant in fungicide action. Using Saccharomyces cerevisiae as a model fungus, we provide evidence that amine fungicide treatment induced cell death by apoptosis. Cell death was concomitant with impaired H+-pumping capacity in vacuole vesicles and dependent on vacuolar proteases. Also, the heterologous expression of the Arabidopsis thaliana main H+-pyrophosphatase (AVP1) at the fungal vacuolar membrane reduced apoptosis levels in yeast and increased resistance to amine fungicides. Consistently, A. thaliana avp1 mutant seedlings showed increased susceptibility to this amine fungicide, particularly at the level of root development. This is in agreement with AVP1 being nearly the sole H+-pyrophosphatase gene expressed at the root elongation zones. All in all, the present data suggest that H+-pyrophosphatases are major determinants of plant tolerance to amine fungicides.España, Ministerio de Ciencia e innovación BFU2004-00843España, Ministerio de Ciencia e innovación, BFU2007-61887España, Ministerio de Ciencia e innovación BFU2010-1562