Analysis of metabolic flux distributions in relation to the extracellular environment in Avian cells

Continuous cell lines that proliferate in chemically defined and simple media have been highly regarded as suitable alternatives for vaccine production. One such cell line is the AG1.CR.pIX avian cell line developed by PROBIOGEN. This cell line can be cultivated in a fully scalable suspension culture and adapted to grow in chemically defined, calf serum free, medium [1]–[5]. The medium composition and cultivation strategy are important factors for reaching high virus titers. In this project, a series of computational methods was used to simulate the cell’s response to different environments. The study is based on the metabolic model of the central metabolism proposed in [1]. In a first step, Metabolic Flux Analysis (MFA) was used along with measured uptake and secretion fluxes to estimate intracellular flux values. The network and data were found to be consistent. In a second step, Flux Balance Analysis (FBA) was performed to access the cell’s biological objective. The objective that resulted in the best predicted results fit to the experimental data was the minimization of oxidative phosphorylation. Employing this objective, in the next step Flux Variability Analysis (FVA) was used to characterize the flux solution space. Furthermore, various scenarios, where a reaction deletion (elimination of the compound from the media) was simulated, were performed and the flux solution space for each scenario was calculated. Growth restrictions caused by essential and non-essential amino acids were accurately predicted. Fluxes related to the essential amino acids uptake and catabolism, the lipid synthesis and ATP production via TCA were found to be essential to exponential growth. Finally, the data gathered during the previous steps were analyzed using principal component analysis (PCA), in order to assess potential changes in the physiological state of the cell. Three metabolic states were found, which correspond to zero, partial and maximum biomass growth rate. Elimination of non-essential amino acids or pyruvate from the media showed no impact on the cell’s assumed normal metabolic state.

Producing on-line ultrapure dialysis fluid.

The process of on-line generation of ultrapure dialysis fluid is a core prerequisite for the safe execution of modern renal replacement therapies such as on-line hemodiafiltration and high-flux hemodialysis. In these extracorporeal treatments with variable degrees of convection, significant volumes of plasma water are removed and replaced with dialysis fluid, which must occur without causing harm to the patient. Historically, on-line generation of sterile and pyrogen-free physiological substitution fluid by the process of membrane ultrafiltration of fresh dialysis fluid has its origin in hemofiltration, a purely convective therapy. Development of this and later therapies is described in the historical context of a successful effort over decades to overcome the above formidable challenge, which was provided jointly by pioneering clinical investigators and a resourceful dialysis industry.

Converter-flux-based current control of voltage source PWM rectifiers - analysis and implementation

Pulsewidth-modulated (PWM) rectifier technology is increasingly used in industrial applications like variable-speed motor drives, since it offers several desired features such as sinusoidal input currents, controllable power factor, bidirectional power flow and high quality DC output voltage. To achieve these features,however, an effective control system with fast and accurate current and DC voltage responses is required. From various control strategies proposed to meet these control objectives, in most cases the commonly known principle of the synchronous-frame current vector control along with some space-vector PWM scheme have been applied. Recently, however, new control approaches analogous to the well-established direct torque control (DTC) method for electrical machines have also emerged to implement a high-performance PWM rectifier. In this thesis the concepts of classical synchronous-frame current control and DTC-based PWM rectifier control are combined and a new converter-flux-based current control (CFCC) scheme is introduced. To achieve sufficient dynamic performance and to ensure a stable operation, the proposed control system is thoroughly analysed and simple rules for the controller design are suggested. Special attention is paid to the estimationof the converter flux, which is the key element of converter-flux-based control. Discrete-time implementation is also discussed. Line-voltage-sensorless reactive reactive power control methods for the L- and LCL-type line filters are presented. For the L-filter an open-loop control law for the d-axis current referenceis proposed. In the case of the LCL-filter the combined open-loop control and feedback control is proposed. The influence of the erroneous filter parameter estimates on the accuracy of the developed control schemes is also discussed. A newzero vector selection rule for suppressing the zero-sequence current in parallel-connected PWM rectifiers is proposed. With this method a truly standalone and independent control of the converter units is allowed and traditional transformer isolation and synchronised-control-based solutions are avoided. The implementation requires only one additional current sensor. The proposed schemes are evaluated by the simulations and laboratory experiments. A satisfactory performance and good agreement between the theory and practice are demonstrated.

Evaluation of the Efficiency of Line-Start Permanent-Magnet Machines as a Function of the Operating Temperature

The standard squirrel-cage induction machine has nearly reached its maximum efficiency. In order to further increase the energy efficiency of electrical machines, the use of permanent magnets in combination with the robust design and the line start capability of the induction machine is extensively investigated. Many experimental designs have been suggested in literature, but recently, these line-start permanent-magnet machines (LSPMMs) have become off-the-shelf products available in a power range up to 7.5 kW. The permanent magnet flux density is a function of the operating temperature. Consequently, the temperature will affect almost every electrical quantity of the machine, including current, torque, and efficiency. In this paper, the efficiency of an off-the-shelf 4-kW three-phase LSPMM is evaluated as a function of the temperature by both finite-element modeling and by practical measurements. In order to obtain stator, rotor, and permanent magnet temperatures, lumped thermal modeling is used.

Spectro-imagerie optique à faible flux et comparaison de la cinématique Ha et HI d'un échantillon de galaxies proches

Un nouveau contrôleur de EMCCD (Electron multiplying Charge Coupled Device) est présenté. Il permet de diminuer significativement le bruit qui domine lorsque la puce EMCCD est utilisé pour du comptage de photons: le bruit d'injection de charge. À l'aide de ce contrôleur, une caméra EMCCD scientifique a été construite, caractérisée en laboratoire et testée à l'observatoire du mont Mégantic. Cette nouvelle caméra permet, entre autres, de réaliser des observations de la cinématique des galaxies par spectroscopie de champ intégral par interférométrie de Fabry-Perot en lumière Ha beaucoup plus rapidement, ou de galaxies de plus faible luminosité, que les caméras à comptage de photon basées sur des tubes amplificateurs. Le temps d'intégration nécessaire à l'obtention d'un rapport signal sur bruit donné est environ 4 fois moindre qu'avec les anciennes caméras. Les applications d'un tel appareil d'imagerie sont nombreuses: photométrie rapide et faible flux, spectroscopie à haute résolution spectrale et temporelle, imagerie limitée par la diffraction à partir de télescopes terrestres (lucky imaging), etc. D'un point de vue technique, la caméra est dominée par le bruit de Poisson pour les flux lumineux supérieurs à 0.002 photon/pixel/image. D'un autre côté, la raie d'hydrogène neutre (HI) à 21 cm a souvent été utilisée pour étudier la cinématique des galaxies. L'hydrogène neutre a l'avantage de se retrouver en quantité détectable au-delà du disque optique des galaxies. Cependant, la résolution spatiale de ces observations est moindre que leurs équivalents réalisés en lumière visible. Lors de la comparaison des données HI, avec des données à plus haute résolution, certaines différences étaient simplement attribuées à la faible résolution des observations HI. Le projet THINGS (The HI Nearby Galaxy Survey a observé plusieurs galaxies de l'échantillon SINGS (Spitzer Infrared Nearby Galaxies Survey). Les données cinématiques du projet THIGNS seront comparées aux données cinématiques obtenues en lumière Ha, afin de déterminer si la seule différence de résolution spatiale peut expliquer les différences observées. Les résultats montrent que des différences intrinsèques aux traceurs utilisées (hydrogène neutre ou ionisé), sont responsables de dissemblances importantes. La compréhension de ces particularités est importante: la distribution de la matière sombre, dérivée de la rotation des galaxies, est un test de certains modèles cosmologiques.

Some Lattice Problems In Fuzzy Set Theory And Fuzzy Topology

It is believed that every fuzzy generalization should be formulated in such a way that it contain the ordinary set theoretic notion as a special case. Therefore the definition of fuzzy topology in the line of C.L.CHANG E9] with an arbitrary complete and distributive lattice as the membership set is taken. Almost all the results proved and presented in this thesis can, in a sense, be called generalizations of corresponding results in ordinary set theory and set topology. However the tools and the methods have to be in many of the cases, new. Here an attempt is made to solve the problem of complementation in the lattice of fuzzy topologies on a set. It is proved that in general, the lattice of fuzzy topologies is not complemented. Complements of some fuzzy topologies are found out. It is observed that (L,X) is not uniquely complemented. However, a complete analysis of the problem of complementation in the lattice of fuzzy topologies is yet to be found out

Reconciling the electron counterstreaming and dropout occurrence rates with the heliospheric flux budget

Counterstreaming electrons (CSEs) are treated as signatures of closed magnetic flux, i.e., loops connected to the Sun at both ends. However, CSEs at 1 AU likely fade as the apex of a closed loop passes beyond some distance R, owing to scattering of the sunward beam along its continually increasing path length. The remaining antisunward beam at 1 AU would then give a false signature of open flux. Subsequent opening of a loop at the Sun by interchange reconnection with an open field line would produce an electron dropout (ED) at 1 AU, as if two open field lines were reconnecting to completely disconnect from the Sun. Thus EDs can be signatures of interchange reconnection as well as the commonly attributed disconnection. We incorporate CSE fadeout into a model that matches time-varying closed flux from interplanetary coronal mass ejections (ICMEs) to the solar cycle variation in heliospheric flux. Using the observed occurrence rate of CSEs at solar maximum, the model estimates R ∼ 8–10 AU. Hence we demonstrate that EDs should be much rarer than CSEs at 1 AU, as EDs can only be detected when the juncture points of reconnected field lines lie sunward of the detector, whereas CSEs continue to be detected in the legs of all loops that have expanded beyond the detector, out to R. We also demonstrate that if closed flux added to the heliosphere by ICMEs is instead balanced by disconnection elsewhere, then ED occurrence at 1 AU would still be rare, contrary to earlier expectations.

Flux comparison of Eulerian and Lagrangian estimates of Agulhas leakage: A case study using a numerical model

Estimating the magnitude of Agulhas leakage, the volume flux of water from the Indian to the Atlantic Ocean, is difficult because of the presence of other circulation systems in the Agulhas region. Indian Ocean water in the Atlantic Ocean is vigorously mixed and diluted in the Cape Basin. Eulerian integration methods, where the velocity field perpendicular to a section is integrated to yield a flux, have to be calibrated so that only the flux by Agulhas leakage is sampled. Two Eulerian methods for estimating the magnitude of Agulhas leakage are tested within a high-resolution two-way nested model with the goal to devise a mooring-based measurement strategy. At the GoodHope line, a section halfway through the Cape Basin, the integrated velocity perpendicular to that line is compared to the magnitude of Agulhas leakage as determined from the transport carried by numerical Lagrangian floats. In the first method, integration is limited to the flux of water warmer and more saline than specific threshold values. These threshold values are determined by maximizing the correlation with the float-determined time series. By using the threshold values, approximately half of the leakage can directly be measured. The total amount of Agulhas leakage can be estimated using a linear regression, within a 90% confidence band of 12 Sv. In the second method, a subregion of the GoodHope line is sought so that integration over that subregion yields an Eulerian flux as close to the float-determined leakage as possible. It appears that when integration is limited within the model to the upper 300 m of the water column within 900 km of the African coast the time series have the smallest root-mean-square difference. This method yields a root-mean-square error of only 5.2 Sv but the 90% confidence band of the estimate is 20 Sv. It is concluded that the optimum thermohaline threshold method leads to more accurate estimates even though the directly measured transport is a factor of two lower than the actual magnitude of Agulhas leakage in this model.

Temporal and spatial variability of mobile fauna on a submarine cliff and boulder scree complex: a community in flux

The mobile component of a community inhabiting a submarine boulder scree/cliff was investigated at Lough Hyne, Ireland at dawn, midday, dusk and night over a 1-week period. Line transects (50 m) were placed in the infralittoral (6 m) and circumlittoral (18 m) zones and also the interface between these two zones (12 m). The dominant mobile fauna of this cliff consisted of echinoderms (6 species), crustaceans (10 species) and fish (23 species). A different component community was identified at each time/depth interval using Multi-Dimensional Scaling (MDS) even though both species diversity (Shannon-Wiener indices) and richness (number of species) remained constant. These changes in community composition provided indirect evidence for migration by these mobile organisms. However, little evidence was found for migration between different zones with the exception of the several wrasse species. These species were observed to spend the daytime foraging in the deeper zone, but returned to the upper zone at night presumably for protection from predators. For the majority of species, migration was considered to occur to cryptic habitats such as holes and crevices. The number of organisms declined during the night, although crustacean numbers peaked, while fish and echinoderms were most abundant during day, possibly due to predator-prey interactions. This submarine community is in a state of flux, whereby, community characteristics, including trophic and energetic relationships, varied over small temporal (daily) and spatial (m) scales.

Interchange reconnection: remote sensing of solar signature and role in heliospheric magnetic flux budget

Interchange reconnection at the Sun, that is, reconnection between a doubly-connected field loop and singly-connected or open field line that extends to infinity, has important implications for the heliospheric magnetic flux budget. Recent work on the topic is reviewed, with emphasis on two aspects. The first is a possible heliospheric signature of interchange reconnection at the coronal hole boundary, where open fields meet closed loops. The second aspect concerns the means by which the heliospheric magnetic field strength reached record-lows during the recent solar minimum period. A new implication of this work is that interchange reconnection may be responsible for the puzzling, occasional coincidence of the heliospheric current sheet and the interface between fast and slow flow in the solar wind.

A GCSS model intercomparison for a tropical squall line observed during toga-coare. II: Intercomparison of single-column models and a cloud-resolving model

This paper presents single-column model (SCM) simulations of a tropical squall-line case observed during the Coupled Ocean-Atmosphere Response Experiment of the Tropical Ocean/Global Atmosphere Programme. This case-study was part of an international model intercomparison project organized by Working Group 4 ‘Precipitating Convective Cloud Systems’ of the GEWEX (Global Energy and Water-cycle Experiment) Cloud System Study. Eight SCM groups using different deep-convection parametrizations participated in this project. The SCMs were forced by temperature and moisture tendencies that had been computed from a reference cloud-resolving model (CRM) simulation using open boundary conditions. The comparison of the SCM results with the reference CRM simulation provided insight into the ability of current convection and cloud schemes to represent organized convection. The CRM results enabled a detailed evaluation of the SCMs in terms of the thermodynamic structure and the convective mass flux of the system, the latter being closely related to the surface convective precipitation. It is shown that the SCMs could reproduce reasonably well the time evolution of the surface convective and stratiform precipitation, the convective mass flux, and the thermodynamic structure of the squall-line system. The thermodynamic structure simulated by the SCMs depended on how the models partitioned the precipitation between convective and stratiform. However, structural differences persisted in the thermodynamic profiles simulated by the SCMs and the CRM. These differences could be attributed to the fact that the total mass flux used to compute the SCM forcing differed from the convective mass flux. The SCMs could not adequately represent these organized mesoscale circulations and the microphysicallradiative forcing associated with the stratiform region. This issue is generally known as the ‘scale-interaction’ problem that can only be properly addressed in fully three-dimensional simulations. Sensitivity simulations run by several groups showed that the time evolution of the surface convective precipitation was considerably smoothed when the convective closure was based on convective available potential energy instead of moisture convergence. Finally, additional SCM simulations without using a convection parametrization indicated that the impact of a convection parametrization in forced SCM runs was more visible in the moisture profiles than in the temperature profiles because convective transport was particularly important in the moisture budget.

Studying the contact point and interface moving in a sinusoidal tube with lattice Boltzmann method

The multicomponent nonideal gas lattice Boltzmann model by Shan and Chen (S-C) is used to study the immiscible displacement in a sinusoidal tube. The movement of interface and the contact point (contact line in three-dimension) is studied. Due to the roughness of the boundary, the contact point shows "stick-slip" mechanics. The "stick-slip" effect decreases as the speed of the interface increases. For fluids that are nonwetting, the interface is almost perpendicular to the boundaries at most time, although its shapes at different position of the tube are rather different. When the tube becomes narrow, the interface turns a complex curves rather than remains simple menisci. The velocity is found to vary considerably between the neighbor nodes close to the contact point, consistent with the experimental observation that the velocity is multi-values on the contact line. Finally, the effect of three boundary conditions is discussed. The average speed is found different for different boundary conditions. The simple bounce-back rule makes the contact point move fastest. Both the simple bounce-back and the no-slip bounce-back rules are more sensitive to the roughness of the boundary in comparison with the half-way bounce-back rule. The simulation results suggest that the S-C model may be a promising tool in simulating the displacement behaviour of two immiscible fluids in complex geometry.

The evolution of the Sun's open magnetic flux: I. a single bipole

In this paper the origin and evolution of the Sun’s open magnetic flux are considered for single magnetic bipoles as they are transported across the Sun. The effects of magnetic flux transport on the radial field at the surface of the Sun are modeled numerically by developing earlier work by Wang, Sheeley, and Lean (2000). The paper considers how the initial tilt of the bipole axis (α) and its latitude of emergence affect the variation and magnitude of the surface and open magnetic flux. The amount of open magnetic flux is estimated by constructing potential coronal fields. It is found that the open flux may evolve independently from the surface field for certain ranges of the tilt angle. For a given tilt angle, the lower the latitude of emergence, the higher the magnitude of the surface and open flux at the end of the simulation. In addition, three types of behavior are found for the open flux depending on the initial tilt angle of the bipole axis. When the tilt is such that α ≥ 2◦ the open flux is independent of the surface flux and initially increases before decaying away. In contrast, for tilt angles in the range −16◦ < α < 2◦ the open flux follows the surface flux and continually decays. Finally, for α ≤ −16◦ the open flux first decays and then increases in magnitude towards a second maximum before decaying away. This behavior of the open flux can be explained in terms of two competing effects produced by differential rotation. Firstly, differential rotation may increase or decrease the open flux by rotating the centers of each polarity of the bipole at different rates when the axis has tilt. Secondly, it decreases the open flux by increasing the length of the polarity inversion line where flux cancellation occurs. The results suggest that, in order to reproduce a realistic model of the Sun’s open magnetic flux over a solar cycle, it is important to have accurate input data on the latitude of emergence of bipoles along with the variation of their tilt angles as the cycle progresses.

Flux transfer events at the magnetopause and in the ionosphere

On December 1, 1986 the ISEE 1 and 2 spacecraft pair passed through the dayside magnetopause at a location which mapped approximately to ionospheric field-line foot-points near the fields of view of the EISCAT radar and photometers and an all-sky camera on Svalbard. The magnetosheath magnetic field was southward and duskward at the time, and flux transfer events (FTEs) were observed at the ISEE location. At the same time, the EISCAT radar observed ionospheric flow bursts of up to 1 km s−1. The peak of each burst followed an FTE observation at ISEE by a few minutes. The bursts, each lasting ten or fifteen minutes, were comprised of first a westward then a poleward flow. An all-sky camera at Ny Ålesund observed dayside auroral breakup forms during or shortly after the flow bursts, moving westward then poleward. While these flow bursts and associated dayside auroral forms have been previously reported in association with southward IMF orientations, this is the first observation of a direct link to FTEs at the magnetopause. On this occasion, the lower limit on the inferred potential associated with the FTEs is roughly 10 kV. Their inferred east-west extent in the ionosphere ranges between 700 and 1000 km, corresponding to a 3 – 5 RE local time extent at the average magnetopause.

The ionospheric signatures of flux transfer events and solar wind dynamic pressure changes

The generation of flow and current vortices in the dayside auroral ionosphere has been predicted for two processes ocurring at the dayside magnetopause. The first of these mechanisms is time-dependent magnetic reconnection, in “flux transfer events” (FTEs); the second is the action of solar wind dynamic pressure changes. The ionospheric flow signature of an FTE should be a twin vortex, with the mean flow velocity in the central region of the pattern equal to the velocity of the pattern as a whole. On the other hand, a pulse of enhanced or reduced dynamic pressure is also expected to produce a twin vortex, but with the central plasma flow being generally different in speed from, and almost orthogonal to, the motion of the whole pattern. In this paper, we make use of this distinction to discuss recent observations of vortical flow patterns in the dayside auroral ionosphere in terms of one or other of the proposed mechanisms. We conclude that some of the observations reported are consistent only with the predicted signature of FTEs. We then evaluate the dimensions of the open flux tubes required to explain some recent simultaneous radar and auroral observations and infer that they are typically 300 km in north–south extent but up to 2000 km in longitudinal extent (i.e., roughly 5 hours of MLT). Hence these observations suggest that recent theories of FTEs which invoke time-varying reconnection at an elongated neutral line may be correct. We also present some simultaneous observations of the interplanetary magnetic field (IMF) and solar wind dynamic pressure (observed using the IMP8 satellite) and the ionospheric flow (observed using the EISCAT radar) which are also only consistent with the FTE model. We estimate that for continuously southward IMF ( ≈ 5 nT) these FTEs contribute about 30 kV to the mean total transpolar voltage (∼30%).