No description available.

The generalized theory of thermoelasticity was employed to characterize the coupled thermal and mechanical wave propagation in high performance microelectronic packages. Application of a Gaussian heat source of spectral profile similar to high performance devices was shown to induce rapid thermal and mechanical transient phenomena. The stresses and temporal gradient of stresses (power density) induced by the thermal and mechanical disturbances were analyzed using the Gabor Wavelet Transform (GWT). The arrival time of frequency components and their magnitude was studied at various locations in the package. Comparison of the results from the classical thermoelasticity theory and generalized theory was also conducted. It was found that the two theories predict vastly different results in the vicinity of the heat source but that the differences diminish within a larger time window. Results from both theories indicate that the rapid thermal-mechanical waves cause high frequency, broadband stress waves to propagate through the package for a very short period of time. The power density associated with these stress waves was found to be of significant magnitude indicating that even though the effect, titled short time scale effect, is short lived, it could have significant impact on package reliability. The high frequency and high power density associated with the stress waves indicate that the probability of sub-micron cracking and/or delamination due to short time scale effect is high. The findings demonstrate that in processes involving rapid thermal transients, there is a non-negligible transient phenomenon worthy of further investigation.

RNA editing had been considered as a rare exception to the central dogma of molecular biology in which the mRNA truthfully carries genetic code from nucleus to the ribosome for translation. However, researches in the last five years have revealed numerous, widespread RNA A-to-I editing sites in human genome. Although the effects of these editing events require further study, this finding strongly suggests RNA editing occurs frequently, and affects large number of genes. By selectively modifying a few sequences of a gene, RNA editing allows a cell to produce a population of proteins with different properties from a single gene. The major question of this thesis study is whether such editing event is actually dynamically regulated when the cellular physiological processes have to be adjusted in response to changing environment. A previous study screening for Drosophila mutants defected in hypoxia and heat tolerance discovered a hypnos-2 mutant strain which was later found to be defective in dADAR, the drosophila gene encoding the A-to-I editing enzyme, supporting the hypothesis that cells/organisms response to stressful environment by dADAR-mediated RNA editing. Two directions are used to approach how Drosophila uses A-to-I editing to adapt ¡§heat¡¨ environment stress. First, whether the expression pattern of dADAR changes after heat shock was investegated. The result showed the dADAR gene exon 7 self-editing frequency was decreased by heat shock, thus possibly enhances dADAR activity after heat shock processing. Moreover it is worth noting that the isoform without -1 exon transcript were obviously up-regulated, and transcript with -1 sequence is relatively down-regulated. On the other hand, no significant changes in the dADAR mRNA expression levels and in the degrees of two dADAR promoters activity were observed. Second, the changes of editing frequency of 30 known A-to-I editing sites were investigated. Generally the editing frequency of majority editing sites changed after heat shock. Therefore, the dADAR activity, the dADAR gene transcript expression alternations, and A-to-I editing frequency of dADAR target genes did change after heat shock, supporting the notion that change of RNA editing pattern is a mechanism for organism to adapt to drastic environmental change. However, how the edited protein isoforms contribute to heat resistance requires further investigation.

Richtmyer-Meshkov instability (RMI) occurs when an interface of two fluids with different densities is impulsively accelerated. The main interest in RMI is to understand the growth of perturbations, and numerous theoretical models have been developed and validated against experimental/numerical studies. However, most of the studies assume very simple initial conditions. Recently, more complex RMI has been studied, and this study focuses on two cases: reshocked RMI and multiphase RMI. It is well known that reshock to the species interface causes rapid growth of interface perturbation amplitude. However, the growth rates after reshock are not well understood, and there are no practical theoretical models yet due to its complex interface conditions at reshock. A couple of empirical expressions have been derived from experimental and numerical studies, but these models are limited to certain interface conditions. This study performs parametric numerical studies on various interface conditions, and the empirical models on the reshocked RMI are derived for each case. It is shown that the empirical models can be applied to a wide range of initial conditions by choosing appropriate values of the coefficient. The second part of the study analyzes the flow physics of multiphase RMI. The linear growth model for multiphase RMI is derived, and it is shown that the growth rates depend on two nondimensional parameters: the mass loading of the particles and the Stokes number. The model is compared to the numerical predictions under two types of conditions: a shock wave hitting (1) a perturbed species interface surrounded by particles, and (2) a perturbed particle cloud. In the first type of the problem, the growth rates obtained by the numerical simulations are in agreement with the multiphase RMI growth model when Stokes number is small. However, when the Stokes number is very large, the RMI motion follows the single-phase RMI growth model since the particle do not rapidly respond while the RMI instability grows. The second type of study also shows that the multiphase RMI model is applicable if Stokes number is small. Since the particles themselves characterize the interface, the range of applicable Stokes number is smaller than the first study. If the Stokes number is in the order of one or larger, the interface experiences continuous acceleration and shows the growth profile similar to a Rayleigh-Taylor instability.

This dissertation focuses on developing a predictive method for determining the dynamic densification behavior of thermite powder mixtures consisting of equivolumetric mixtures of Ta + Fe₂O₃ and Ta + Bi₂O₃. Of primary importance to these highly reactive powder mixtures is the ability to characterize the stress at which full compaction occurs, the crush strength, which can significantly influence the stress required to initiate reaction during dynamic or impact loading. Examined specifically are the quasi-static and dynamic compaction responses of these mixtures. Experimentally obtained compaction responses in the quasi-static regime are analyzed using available compaction models, and an analysis technique is developed that allows for a correct measurement of the apparent yield strength of the powder mixtures. The correctly determined apparent yield strength is combined with an equation of state to yield a prediction of the shock densification response, including the dynamic crush strength of the thermite powder mixtures. The validated approach is also extended to the Al + Fe₂O₃ thermite system. It is found that accurate predictions of the crush strength can be obtained through determination of the apparent yield strength of the powder mixture when incorporated into the equation of state. It is observed that the predictive ability in the incomplete compaction region is configurationally dependent for highly heterogeneous thermite powder systems, which is in turn influenced by particle morphology and differences in intrinsic properties of constituents (density, strength, etc.).

Hest shock protein 70 (Hsp70) class of chaperones is highly conserved and present ubiquitously in all cellular organisms They play important role in folding of nascent polypeptides and translocation of precursor proteins to endoplasmic reticulum, mitochondria and chloroplast Hsp70 assists in assembly of proteins complexes as well as in disassembly e g uncoatmg of clathrin coated vesicles Chaperone function of Hsp70 is modulated by cochaperones of DnaJ class, Hip, Hop etc Hsp70 is a component of multi chaperone complex with Hsp90 and helps in maturation of kinases or transcription factors. Plasmodium falciparum is responsible for most severe form of human malaria Plasmodmm in its intraerythrocytic cycle presents an example of a cell with multiple, complex membrane bound structures both inside the parasite as well as m the infected erythrocyte cytosol Parasite deploys proteins in host erythrocyte cytosol, at erythrocyte plasma membrane or traffics them for secretion outside the infected cell in addition to trafficking of proteins to its own organelles like mitochondria, apicoplast, food vacuole, ER etc It is of interest to malaria biologists to understand these trafficking events and role of chaperones in regulating them This study was aimed at understanding the function(s) of Hsp70 in Plasmodium infected erythrocyte in protein maturation and trafficking events We have attempted to study Hsp70 chaperone present in Plasmodium infected erythrocytes We have largely focused on the cytosohc Hsp70, PfHsp70, in the parasite and systematically analyzed its expression, localization, abundance and complexes in the intraerythrocytic cycle To gain insight into its function, we have identified a subset of PfHsp70 interacting proteins, parasite Hsp90, Hsp70-3, Hsp60 and beta tubulin by coimmunoprecipitation experiments in conjunction with proteomic tools like 2DGE and mass spectrometry Parasite Hsp60 is a mitochondria-targeted protein and we have examined the involvement of PfHsp70 in translocation of Hsp60 precursor protein to parasite mitochondrion PfHsp70 and PfHsp90 were found to be present in a complex Geldanarnycm, a drug that affects Hsp70-Hsp90 complex, was used to investigate the role of PfHsp70 in parasite protein trafficking Since there are no known parasite derived chaperones in erythrocyte cytosol compartment, we have examined the possible "involvement of host Hsp70 in supporting transport and assembly of parasite proteins in erythrocyte cytosol Hsp70 in Plasmodium falciparum intraerythrocytic cycle P. falciparum genome codes for five Hsp70 homologs Two of these, pfHsp70-l and PfBiP are expressed in intraerythrocytic stage and have been localized to nucleocytoplasmic and endoplasmic reticulum fraction of the parasite respectively We have focused this study on PfHsp70 of the parasite We show that PfHsp70 is an abundant protein in the cytosol constituting about 2% of the total soluble pool It gets further induced during stress like heat shock and translocates to nuclear fraction indicating that PfHsp70 may be involved in protective function in the parasite nucleus during stress Nuclear translocation of mammalian Hsp70 during stress has been linked to its phosphorylation at Tyr524 We found PfHsp70 to be phosphorylated by in vivo phosphate labeling m the parasite Analysis of PfHsp70 by 2-dimensional gel electrophoresis on narrow gradient IPG strips indicated that it exists in four forms differing in their isoelectnc points (pi) Phosphatase treatment combined with analysis using a phosphorylation prediction tool,Proteomod (http //www biochem use ernet in/proteomod html) suggested that PfHsp70 is phosphorylated at three residues in the parasite The extent of phosphorylation of PfHsp70 may determine substrate specificity or subcellular localization or both Using 2DGE and mass spectrometry approach, we also identified chaperones like Hsp909 BiP, Hsp60, and protein disulphide isomerase (PDI) m P falciparum proteome In summary, PfHsp70 appears to be a highly abundant, cytosohc chaperone It is inducible by stress and multiply phosphorylated and is likely to participate in multiple processes in the parasite. PfHsp70 complexes and interacting proteins in the parasite To gam insight into the functions of Hsp70, we looked for PfHsp70 interacting proteins in the parasite We used gel filtration chromatography to resolve and enrich PfHsp70 complexes and also employed coimmunoprecipitation approach to identify interacting proteins We found parasite Hsp90, Hsp70-3, Hsp60 and beta-tubulin interact with PfHsp70 Fractionation of parasite lysate indicated that PfHsp70 is present in two major complexes of 200 kDa and 450 kDa We find that PfHsp90 interacts with PfHsp70 and both are present in 450 kDa complex Our analysis indicated that 450-kDa complex is like Hsp70-Hsp90 multichaperone complex described in mammalian cells while 200 kDa complex is likely to be an Hsp70-cochaperone complex Smaller complex appears to be a precursor for multichaperone complex Use of an Hsp90 inhibitor, geldanamycin (GA), to study the function of this multi chaperone showed that GA inhibits parasite growth Maturation of four phosphoproteins interacting with PfHsp70 was affected by GA implicating them in regulation of parasite growth GA appeared to mediate its effects by inhibiting H§p^0 phosphorylation Amongst the other three interacting proteins, PfHsp70-3 is amoveJ/Hsp70 homolog that was found at the protein level for the first time in this study PfHsp60 is mitochondria-targeted protein in the parasite and it is likely that cytoshc PfHsp70 helps in translocation of PfHsp60 to mitochondria from cytosol Tubuhn is a cytoskeletal protein and its interaction with PfHsp70 suggests possible role of PfHsp70 in cytoskeleton organization during invasion, growth or cell division In all, we find that Hsp70 in the parasite exist in a multi chaperone complex with Hsp90 which might be responsible for maturation of signaling molecules important for growth The smaller complex of PfHsp70 is a precursor of multi chaperone complex and is likely to be an Hsp70- co chaperone complex Role of Hsp70 in protein translocation and trafficking Cytosolic Hsp70 aids in translocation of precursor proteins from cytosol to mitochondria (or chloroplast) We found a mitochondnal chaperone, PfHsp60, interact with PfHsp70 and we examined the possibility that PfHsp60 translocation is assisted by cytosolic PfHsp70 We found that PfHsp60 had a cleavable, N-thermal targeting sequence Examination of PfHsp60 forms present in mitochondnal and cytosolic fraction of the parasite showed that mitochondnal form was more acidic in pi than cytosolic form as expected after targeting sequence cleavage Cytosolic PfHsp60 interacted with both PfHsp70 and PfHsp90 Interestingly, while mitochondnal PfHsp60 appeared to be in a chaperonm like complex, as expected, cytosolic form was present in smaller ohgomeric complex of about 450 kDa This suggested that PfHsp60 precursor form could be bound to multichperone complex All these experiments together strongly indicated that PfHsp60 precursor interacts with cytosolic Hsp70 and Hsp90 before former's translocation into mitochondria This interaction might be required to keep the precursor in the transport competent state P falciparum lives inside a vacuole in the infected cells but it deploys a number of proteins to host cell cytosol and to the plasma membrane To examine the involvement of multichaperone complex in trafficking, we studied the effect of GA on targeting of two parasite proteins, knob associated histidme-rich protein (KAHRP) and glycogen synthase kinase (GSK) KAHRP is indispensable for the formation of cytoadherence complexes called knobs at erythrocyte plasma membrane We found that KAHRP transport to erythrocyte plasma membrane was blocked in GA-treated parasites and it appeared all over the infected cell Further analysis showed that GA caused block in KAHRP transport at some step beyond its exit from parasite ER The targeting of GSK to membranous inclusions in the infected RBC cytosol was not severely affected m the GA-treated parasites suggesting that GSK transport may not be regulated by multi chaperone complex It also indicated that parasite may be using different pathways for trafficking of proteins to the host compartment In summary, PfHsp70 and PfHsp90 interact with PfHsp60 precursor in the cytosol They probably help keep the precursor in transport competent form before arrival at the translocase complex of mitochondria The multi chaperone complex may also be important for trafficking of at least one parasite protein, KAHRP, to the host cell compartment Analysis of erythrocyte Hsp70 in Plasmodium falciparum infected cells The remodeled plasma membrane of parasite-infected erythrocytes is important for the cytoadherence property of the infected cells Knobs, supramolecular complexes on the infected cell surface, formed by parasite proteins, PfEMPl, KAHRP, and PfEMP3 are responsible for cytoadherence of infected cells to vascular endothehum or placenta KAHRP transport is BFA-sensitive inside the parasite while PfEMP proteins undergo vesicle mediated trafficking in the erythrocyte cytosol The involvement of molecular chaperones has been implicated in the trafficking and assembly of knob components in the erythrocyte cytosol There is no evidence for the presence of bona fide parasite derived chaperones in the host compartment The chaperones of the erythrocyte origin, Hsp70, Hsp90, Hip and Hop were readily detected in the host cytosol, on the other hand By analyzing localization, abundance and biochemical characteristics of the host chaperones of erythrocyte origin, we examined if host chaperones are being utilized by the parasite for its functions Localization experiment showed that while PfHsp70, PfHsp90 and PfBiP were present in the parasite compartment, host-Hsp70 was present in erythrocyte cytosol fraction Host~Hsp70 was about 60% as abundant as PfHsp70 and was potentially capable of facilitating chaperone function in the erythrocyte cytosol Though host-Hsp70 was soluble in unmfected cells, it was present in membrane bound, triton-insoluble complexes, containing KAHRP, in infected cells Since knobs are triton-insoluble complexes at the erythrocyte plasma membrane, we isolated erythrocyte ghost (plasma membrane) fraction and could detect both Hsp70 and KAHRP Hsp70 association with erythrocyte plasma membrane was specific as it could be crosshnked to KAHRP in ghost fraction of infected cells Host-hsp70 was present in purified cytoskeleton fraction containing knobs from infected cells along with cochaperone Hop All these evidences suggest that parasite may be exploiting host-Hsp70 in erythrocyte cytosol compartment Summary This study gives insight into some functions performed by PfHsp70 in mtraerythrocytic cycle of malarial parasite PfHsp70 is an abundant cytosohc chaperone in the parasite It gets induced during stress and translocates to the nucleus It is also phosphorylated at three sites Analysis of Pfhsp70 complexes shows that it is present in bimodal complexes (450 kDa and 200 kDa), which are in equilibrium PfHsp70 and PfHsp90 interact and are part of 450 kDa multichaperone complex This multichaperone complex appears to regulate trafficking of one parasite protein to host cytosol compartment In addition, PfHsp70 and PfHsp90 are also bound to mitochondria-targeted PfHsp60 precursor in the cytosol probably keeping them m a transport competent state In addition to PfHsp90 and PfHsp60, PfHsp70 interacts with a novel Hsp70 homolog of the parasite, PfHsp70-3, and cytoskeletal protein, beta-tubuhn Examination of chaperones available in erythrocyte cytosol, showed that parasite chaperones were absent while host chaperone (Hsp70) was present and exhibited altered properties during parasite infection It was associated with membrane-bound, triton-insoluble complexes on the infected cell plasma membrane suggesting that host-Hsp70 might be involved in trafficking and/or assembly of parasite proteins In all, PfHsp70, as part of multichaperone complex, appears to be regulating translocation and trafficking of parasite proteins to organellar locations or outside the parasite Host-Hsp70, in erythrocyte cytosol, might also be engaged in specific chaperone function upon infection

In der Reaktorsicherheitsforschung sind auftriebsgetriebene Strömungen von Relevanz für Störfall-szenarien mit Verdünnung der Borkonzentration und für thermische Schockbelastungen des Reak-tordruckbehälters. In der numerischen Simulation der Strömungen werden neben der Berücksichtigung der Auftriebskräfte Quell- und Korrekturterme in die Bilanzgleichungen für die turbulente Energie und die turbulente Dissipation eingeführt. Es wurden erweiterte Modelle entwickelt, in die zusätzliche Gleichungen für die Turbulenzgrößen turbulenter Massenstrom und Dichtevarianz eingehen. Die Modelle wurden in den CFD-Code ANSYS-CFX implementiert. Die Validierung der Modelle erfolgte an einem speziellen Versuchsaufbau (VeMix-Versuchsanlage), mit Einspeisung von Fluid höherer Dichte in eine Vorlage. Als Kriterien für die Validierung wurde der Umschlag zwischen impulsdominiertem Strömungsregime mit vertikalem Jet oder ein vertikales Absinken bei Dominanz von Dichteeffekten herangezogen sowie lokale Konzentrationsmessungen mit Hilfe eines speziell entwickelten Leitfähigkeits-Gittersensors. Eine Verbesserung der Simulation dichtedominierter Vermischungsprozesse mit den erweiterten Turbulenzmodellen konnte allerdings nicht nachgewiesen werden, da die Unterschiede zwischen den Rechnungen mit verschiedenen Turbulenzmodellen zu gering sind. Andererseits konnte jedoch die Simulation der Stratifikation von Fluiden unterschiedlicher Dichte im kalten Strang einer Reaktoranlage deutlich verbessert werden. Anhand der Nachrechnung von Ver-suchen am geometrisch ähnlichen Reaktor-Strömungsmodell ROCOM wurde gezeigt, dass diese Stratifikation von bedeutendem Einfluss auf die Vermischung und somit letztendlich auch auf die Temperatur- bzw. Borkonzentrationsverteilung innerhalb des Reaktordruckbehälters ist. Sie lässt sich nur korrekt simulieren, wenn ausreichend große Abschnitte des kalten Stranges mit modelliert werden. Somit konnte doch eine bessere Vorhersagegenauigkeit der Simulation der Vermischung erreicht werden. In reactor safety research, buoyancy driven flows are of relevance for boron dilution accidents or pressurised thermal shock scenarios. Concerning the numerical simulation of these flows, besides of the consideration of buoyancy forces, source and correction terms are introduced into the balance equations for the turbulent energy and its dissipation rate. Within the project, extended turbulence models have been developed by introducing additional balance equations for the turbulent quantities turbulent mass flow and density variance. The models have been implemented into the computati-onal fluid dynamics code ANSYS-CFX. The validation of the models was performed against tests at a special experimental set-up, the VeMix facility, were fluid of higher density was injected into a vertical test section filled with lighter fluid. As validation criteria the switching-over between a momentum controlled mixing pattern with a horizontal jet and buoyancy driven mixing with vertical sinking down of the heavier fluid was used. Additionally, measurement data gained from an especially developed conductivity wire mesh sensor were used. However, an improvement of the modelling of buoyancy driven mixing by use of the extended models could not be shown, because the differences between calculations with the different models were not relevant. On the other hand, the modelling of the stratification of fluids with different density in the cold leg of a reactor primary circuit could be significantly improved. It has been shown on calculations of experi-ments at the ROCOM mixing test facility, a scaled model of a real reactor plant, that this stratification is relevant as a boundary condition for the mixing process inside the reactor pressure vessel. It can be correctly simulated only if sufficient large parts of the cold legs are included in the modelling. On this way, an improvement of the accuracy of the prediction of mixing processes was achieved.

This paper describes the analytical work done by modelling and evaluating a thermal shock in a WWER-440 reactor pressure vessel due to an emergency case. An axial oriented semielliptical underclad/surface crack is assumed to be located in the core weld line. Threedimensional finite element models are used to compute the global transient temperature and stress-strain fields. By using a three-dimensional submodel, which includes the crack, the local crack stress-strain field is obtained. With a subsequent postprocessing using the j-integral technique the stress intensity factors KI along the crack front are obtained. The results for the underclad and surface crack are provided and compared, together with a critical discussion of the VERLIFE code.

No description available.

<p>Vehicles with internal combustion (IC) engines fueled by hydrocarbon compounds have been used for more than 100 years for ground transportation. During the years and in particular in the last decade, the environmental aspects of IC engines have become a major political and research topic. Following this interest, the emissions of pollutants such as NO_x, CO₂ and unburned hydrocarbons (UHC) from IC engines have been reduced considerably. Yet, there is still a clear need and possibility to improve engine efficiency while further reducing emissions of pollutants. The maximum efficiency of IC engines used in passenger cars is no more than $40\%$ and considerably less than that under part load conditions. One way to improve engine efficiency is to utilize the energy of the exhaust gases to turbocharge the engine. While turbocharging is by no means a new concept, its design and integration into the gas exchange system has been of low priority in the power train design process. One expects that the rapidly increasing interest in efficient passenger car engines would mean that the use of turbo technology will become more widespread. The flow in the IC-engine intake manifold determines the flow in the cylinder prior and during the combustion. Similarly, the flow in the exhaust manifold determines the flow into the turbine, and thereby the efficiency of the turbocharging system. In order to reduce NO_x emissions, exhaust gas recirculation (EGR) is used. As this process transport exhaust gases into the cylinder, its efficiency is dependent on the gas exchange system in general. The losses in the gas exchange system are also an issue related to engine efficiency. These aspects have been addressed up to now rather superficially. One has been interested in global aspects (e.g. pressure drop, turbine efficiency) under steady state conditions.In this thesis, we focus on the flow in the exhaust port and close to the valve. Since the flow in the port can be transonic, we study first the numerical modeling of such a flow in a more simple geometry, namely a bump placed in a wind tunnel. Large-Eddy Simulations of internal transonic flow have been carried out. The results show that transonic flow in general is very sensitive to small disturbances in the boundary conditions. Flow in the wind tunnel case is always highly unsteady in the transonic flow regime with self excited shock oscillations and associated with that also unsteady boundary-layer separation. To investigate sensitivity to periodic disturbances the outlet pressure in the wind tunnel case  was varied periodically at rather low amplitude. These low amplitude oscillations caused hysteretic behavior in the mean shock position and appearance of shocks of widely different patterns. The study of a model exhaust port shows that at realistic pressure ratios, the flow is transonic in the exhaust port. Furthermore, two pairs of vortex structures are created downstream of the valve plate by the wake behind the valve stem and by inertial forces and the pressure gradient in the port. These structures dissipate rather quickly. The impact of these structures and the choking effect caused by the shock on realistic IC engine performance remains to be studied in the future.</p> / CICERO