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<p>In this thesis I explore dimensions through which changes in expectations can serve as a driver of business cycles in a rational expectations setting. Exploiting both the ``sunspot'' and ``news-shock'' approaches to expectations-driven business cycles, I use various theoretical models to investigate how changes in expectations may have played a role in macroeconomic events such as the technological revolution of the 1990's and the financial boom and bust of 2003-2008.</p> <p>In the first chapter, I explore the ability of a model with knowledge capital to generate business cycles driven by expectations of future movement in total factor productivity (TFP). I model knowledge capital as an input into production which is endogenously produced through a learning-by-doing process. When firms receive news of an impending productivity increase, the value of knowledge capital rises, inducing the firm to hire more hours to ``invest'' in knowledge capital. The rise in the value of knowledge capital immediately raises the value of the firm, causing an appreciation in stock prices. If the expected increase in productivity fails to materialize, the model generates a recession as well as a crash in the stock market.</p> <p>In the second chapter, I explore the extent to which expectations about innovations in the financial sector may have contributed to both the boom and bust associated with the ``Great Recession''. Making a connection between the ``boom-years'' of easy credit and the crises of 2008, I argue that agents' overly-optimistic expectations of the benefits associated with financial innovation led to a flood of liquidity in the financial sector, lowering interest rate spreads and facilitating the boom in asset prices and economic activity. When the events of 2007-2009 led to a re-evaluation of the effectiveness of these new products, agents revised their expectations regarding the actual efficiency gains available to the financial sector and this led to a withdrawal of liquidity from the financial system, a reversal in credit spreads and asset prices and a bust in real activity. Following the news-shock approach, I model the boom and bust cycle in terms of an expected future fall in the costs of bankruptcy which are eventually not realized. The build up in liquidity and economic activity in expectation of these efficiency gains is then abruptly reversed when agents' hopes are dashed. The model generates counter-cyclical movement in the spread between lending rates and the risk-free rate which is driven purely by expectations, even in the absence of any exogenous movement in bankruptcy costs as well as an endogenous rise and fall in asset prices and leverage.</p> <p>In the final chapter, I explore the extent to which a ``bout of optimism'' during a period of technological change such as the 1990's could produce not just a boom in consumption, investment and hours-worked, but also rapid growth in productivity itself. I present a theoretical model where the economy endogenously adopts the technological ideas of a slowly evolving technological frontier, and show that the presence of a ``technological gap'' between unadopted ideas and current productivity can lead to multiple equilibria and therefore the possibility that changes in beliefs can be self-fulfilling, often referred to as sunspots. In the model these sunspots take the form of beliefs about the value of adopting the new technological ideas, and unleash both a boom in aggregate quantities as well as eventual productivity growth, increasing the value of adoption and self-confirming the beliefs. In this sense, the model provides an alternative interpretation of the empirical news-based results that identify expectational booms that precede growth in TFP. Finally, I demonstrate that the scope for the indeterminacies is a function of the steady-state growth rate of the underlying frontier of technological ideas, and that during times of low growth in ideas or technological stagnation, the potential for indeterminacies and thus belief-driven productivity growth diminishes.</p> / Doctor of Philosophy (PhD)

Part 1 The coupled shock-tube/mass spectrometer apparatus is characterized in terms of its capabilities for chemical kinetic studies. Criteria for doing kinetic measurements by this experimental technique are discussed. The characterization experiments showed that our apparatus was capable of giving plausible signal shapes for non-reactive dynamic shots at P₁ = 5 torr. Measurements of ion current under static conditions showed that response of the quadrupole mass spectrometer was linear over a range of P₁ = 0-5 torr. Schlieren measurements indicated that the shock wave velocity was erratic and non-reproducible over the last 5 feet of the test section and that the velocity at the endwall could not be predicted from the schlieren data. The electron beam width was found to be ~.1" and the implications of this measurement for further studies on the free jet are outlined. The present beam width is suitable for jet studies in which bulk ionization of gas from a cross-section of the jet is performed. Design improvements needed for future reactive studies on our system are reviewed. In addition, experimental studies of jet risetime with a pulsed molecular beam apparatus showed poor agreement between the experimental and theoretical jet risetimes. The apparent discrepancy is discussed and possible explanations for it are given. Part 2 The rate constant k₁ for the reaction C₅H₁₂ → C₄H₉ + CH₃ was determined from reflected shock experiments (1100-1300°K) in which the progress of reaction was monitored by the appearance of H atoms. Atomic resonance absorption spectrophotometry at the Lyman-α line was performed on three mixtures (20 ppm, 10 ppm, 5 ppm) of neopentane in argon to give k₁ = .17 x 10¹⁸ exp (-84800±6200/RT) sec⁻¹. This result is in very good agreement with earlier single pulse shock tube experiments. In addition, calibration experiments for H atom were performed by shock-heating two mixtures (10 ppm and 5 ppm) of neopentane in argon. The results obtained were in good agreement with previous calibration data. / Doctor of Philosophy

Approved for public release, distribution is unlimited / Evaluations, otherwise known as ship shock trials, have been conducted in order to determine the seaworthiness of each new class of ship commissioned in the U.S. Fleet. While beneficial in determining the overall survivability of a ship and its mission essential equipment in a severe shock environment, these Navy-mandated tests pose serious danger to the crew, ship and environment. As an alternative to these labor intensive, costly and time consuming at-sea tests, the recent advances in computer processing power have made it possible to employ finite element methods involving complex geometries in the modeling and simulation of shock response for the ship and surrounding fluid. This thesis examines the accuracy of shock simulation predictions as compared to the ship shock trials conducted on USS WINSTON S. CHURCHILL (DDG-81). An investigation of the effects of sensor location, damping and shot geometry is presented as validation of the Naval Postgraduate School modeling and simulation methodology. / Lieutenant, United States Navy

Small heat shock proteins (sHSPs) are a ubiquitous family of molecular chaperones that play a vital role in maintaining protein homeostasis in cells. They are the first line of defence against the detrimental effects of cellular stress conditions like fluctuations in temperature, pH, oxidative and osmotic potentials, heavy metal toxicity, drought and anoxia. Many sHSPs are also constitutively expressed during developmental stages of different plant tissues. Members of this family are ATP-independent chaperones, with monomeric masses varying from 12-40 kDa. A characteristic feature of sHSPs is their ability to assemble into large oligomers, ranging from dimers to 48-mers. Under stress conditions, these oligomers dissociate and/or undergo drastic conformational changes to facilitate their binding to misfolded substrate proteins in the cell. This interaction prevents the substrate from aggregating during stress. When physiological conditions are restored, the substrates are transferred to other ATP-dependent heat shock proteins for refolding. Thus sHSPs do not refold their substrates, but instead prevent them from aggregating and maintain them in a „folding-competent‟ state. The clientele of sHSPs includes proteins with a wide range of molecular masses, secondary structures and pIs. This promiscuity has led to sHSPs occupying key positions in the protein quality control network. As molecular chaperones that protect proteins, sHSPs prevent disease. Concomitantly, mutations in sHSPs have also been linked to various human diseases. Till date, high resolution crystal structures are available only for 3 sHSP oligomers. This insufficiency of structural information has hindered our understanding of the mechanism of chaperone function, the link between the oligomeric status and chaperone activity, identification of substrate binding sites and the role of the flexible terminal segments in mediating both the oligomerization and chaperone function. We undertook structural and functional characterization of plant and bacterial sHSPs in order to address some of these questions. Chapter 1 of this thesis gives an overview of the sHSP family, with special emphasis on the oligomeric assemblies of sHSPs of known structures. We highlight what we know about this family through mutational studies, what is as yet unknown, and why it is important to study this family. Chapter 2 describes our efforts at structural and functional characterization of 5 sHSPS in rice, each targeted to a different organelle. We probed the role played by the N-terminal region in mediating oligomer assembly and in the chaperone activity of the protein. Rice sHSPs displayed a wide range of hydrodynamic radii, from 4 nm to 14 nm, suggesting that their oligomeric assemblies are likely to be diverse. In chapter 3, we discuss our attempts at the structural characterization of a bacterial sHSP, Aggregation suppressing protein A, or AgsA from Salmonella enterica. We obtained a high resolution crystal structure of the dimer of the core sHSP domain. We compared this dimer with other known sHSP dimers, reported the deviations that we observed and analysed the structure to account for these differences. We used this dimer structure to successfully obtain solutions for low resolution X-ray diffraction data for oligomers of different truncated constructs of AgsA. We observed that a C-terminal truncated construct formed an octahedral 24¬mer (4.5 Å resolution), whereas a construct truncated at both termini formed a triangular bipyramidal 18-mer (7.7 Å resolution), an assembly hitherto unobserved for any sHSP. A similar 18-mer was obtained when the C-terminal truncated construct was incubated with a dipeptide prior to crystallisation (6.7 Å resolution). The cryo-EM map of the wild type protein (12 Å resolution) could be fitted with a different 18-mer. The low resolution of the data pre-empted an atomic-level description of the interfaces of the assemblies. However, our work highlights the structural plasticity of this protein and probes the sensitivity of the oligomeric assembly to minor differences in construct length.

Molecular chaperones are proteins that interact with and aid in stabilization and activation of other proteins. Chaperones help proteins attain their three dimensional conformation, without forming a part of the final structure. Many of the chaperones are stress proteins known as Heat shock proteins (Hsps). Their expression is upregulated in response to various kinds of stress such as heat stress, oxidative stress etc., which threaten the protein homeostasis, by structurally destabilizing cellular proteins, and increasing the concentration of aggregation-prone folding intermediates. The Hsps are classified according to their molecular weight into Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and the small Hsp families. Some of them are constitutively expressed and play a fundamental role in de novo protein folding. They further aid in proteome maintenance by assisting in oligomeric assembly, protein trafficking, refolding of stress denatured protein, preventing protein aggregation and protein degradation. Heat shock protein 90 (Hsp90) are one of the important representatives of this class of proteins. Hsp90 are highly conserved class of molecular chaperones. They are found in bacteria, eukaryotes, but not in archaea. In contrast to the eukaryotes which require a functional cytoplasmic Hsp90 for viability, the bacterial counterpart (HtpG) is typically nonessential. Hsp90 is an ATP dependent chaperone. Hsp90 form dimers, with each protomer consisting of three functional domains: N- terminal, ATP binding domain, Middle domain and C-terminal domain. Hsp90 is a dynamic protein, and undergoes an elaborate conformational cycle during its ATPase cycle, which is essential for its chaperoning activity. The Hsp90 chaperone cycle is regulated by interaction with diverse cochaperones. Hsp90 interacts with specific set of substrate proteins. Many of these substrate proteins function at the heart of several cellular processes like signalling, cell cycle, apoptosis. Studies from protozoans like Leishmania, Plasmodium, Trypanosoma etc. have also implicated the role of Hsp90 in their growth and stage transitions. Thus, selective inhibition of Hsp90 has been explored as an intervention strategy against important human diseases such as cancer, malaria and other protozoan diseases. The ATP binding N-terminal domain (NTD), has been explored as the target domain for inhibition of Hsp90 using competitive inhibitors of ATP. Several chemical classes of Hsp90 inhibitors are known, including ansamycins, macrolides, purines, pyrazoles, and coumarin antibiotics. However, many inhibitors are observed to be toxic, less soluble and unstable. Hence, there is a requirement for new approach to design inhibitors which are more soluble and less toxic and serve as effective therapeutic drugs.inhibitors are observed to be toxic, less soluble and unstable. Hence, there is a requirement for new approach to design inhibitors which are more soluble and less toxic and serve as effective therapeutic drugs. The work presented in this thesis mainly concerns with the structural studies and biochemical and biophysical characterization of Hsp90 from two different sources viz. Dictyostelium discoideum, a cellular slime mould and a plant source Oryza sativa (rice). The structural analyses of these two proteins have been carried out by X-ray crystallography. Though yeast has been explored extensively as a model system to understand the different roles of Hsp90, it lacks the various signalling pathways essential for growth and development present in case of higher eukaryotes. D. discoideum has been employed as a model system to understand multicellular development, which occurs in response to starvation induced stress. D. discoideum has the advantages due to its ease of manipulation. The organism's genome also shows many signalling pathway for growth and differentiation that are conserved between D. discoideum and mammals. With this motivation, we have studied several structural aspects of the cytosolic isoform of Hsp90 from D. discoideum called HspD. HspD was also observed to play a role in the multicellular development of D. discoideum. It has been demonstrated that the treatment of D. discoideum with inhibitors like Geldanamycin or Radicicol causes an arrest in the multicellular development at the mound stage, and the few which escaped this arrest gave rise to abnormal fruiting bodies. A subset of the proteins involved in this mound arrest phenotype, were observed to have homologs in humans, which are clients of Hsp90. Therefore, a structural perspective of HspD can aid in better understanding of the role of this protein in the organism, as well as, elucidate any structural differences observed as compared to other species, which may have an impact on its activity. Studies on the physiological role of Hsp90 in plants began much later as compared to fungi and humans. In plants Hsp90 are involved in various abiotic stress responses. In addition, their roles have also been implicated in plant growth and development, innate immune response and buffering genetic variations. However, the molecular mechanisms of these various actions are not clearly understood. Also, the structural aspects of plant Hsp90 are yet to be explored. The structure of the NTD of Hsp90 from barley is the only one available from a plant source till now. We have initiated the studies on rice Hsp90 with the objective to understand the mechanism of Hsp90 in plants, which may aid in improving stress tolerance in plants. The thesis has been divided into five chapters. The first chapter introduces the various aspects of Hsp90 protein. The chapter starts with a general overview of concept of molecular chaperones and describes briefly the different classes of molecular chaperones. This is followed by a detailed description of different aspects of Hsp90 with main emphasis on the structure and its conformational flexibility. The chapter describes the association of Hsp90 with other accessory proteins like cochaperones and its interaction with its substrate proteins and explains the functional significance of Hsp90 as a drug target and the need for the development of new class of inhibitors, followed by the significance of the study of Hsp90 in the two model systems (D. discoideum and rice) chosen to be studied. The second chapter gives a brief overview of the principles behind the different experimental methods employed during the course of this research, which includes the tools of X-ray crystallography and other biochemical and biophysical techniques employed for the characterization of the protein. Chapter 3 describes the crystal structure of NTD of Hsp90 from D. discoideum. The structure of NTD was solved in two different native (ligand-free) forms viz. monoclinic and hexagonal. The two forms differed in local structural rearrangement of a segment of NTD known as the lid region. The lid region in the hexagonal form showed a shift in its position as compared to the other solved structures of NTD. The structure of NTD was also solved in complex with various ligands which include ADP, substrate analogs and an inhibitor molecule. A comparison of all the structures showed that the overall structure is well-conserved. One of the crystal structures of NTD showed a heptapeptide (part of the vector) bound at the active site. The peptide was observed to make several complementary interactions with the residues of the ATP binding pocket and retain several interactions which the nucleotide makes with the NTD. The NTD showed subtle conformational differences when compared with the NTD of Hsp90 from yeast. Chapter 4 details the structural and functional characteristics of full length Hsp90 protein from D. discoideum. Due to the large size and flexibility, the full length protein did not crystallize in spite of several attempts. Hence, HspD was studied using different solution studies like Small Angle X-ray Scattering (SAXS) and Dynamic Light Scattering (DLS). Both the studies showed the presence of higher oligomers. The SAXS data showed the presence of tetramers and hexamers while, the addition of the ligand shifts the protein from a dimer to a higher oligomer as observed from DLS studies. The chapter also describes the study of interaction of HspD with a cochaperone protein p23. The interactions were studied using ITC, which showed a strong binding. The ATPase activity was also evaluated in the presence of increasing concentrations of p23, which was observed to decline with increasing concentrations of p23. In chapter 5, we describe the biochemical characterization of Hsp90 from Oryza sativa (rice) and the crystallographic analysis of its NTD. Binding of the rice Hsp90 to ATP and an inhibitor were studied by fluorescence. The ATPase activity of rice Hsp90 was checked by radioactive assay and the protein was observed to be active. The NTD of rice Hsp90 crystallized as a monomer in complex with a substrate analog AMPPCP and the structure was determined.

For flights beyond Mach 6 ramjets are inefficient engines due to huge total pressure loss in the normal shock systems, combustion conditions that lose a large fraction of the available chemical energy due to dissociation and high structural loads. However if the flow remains supersonic inside the combustion chamber, the above problems could be alleviated and here the concept of SCRAMJET(supersonic combustion ramjet) comes into existence. The scramjets could reduce launching cost of satellites by carrying only fuel and ingesting oxygen from atmospheric air. Further applications could involve defense and transcontinental hypersonic transport. In the current study an effort is made to achieve supersonic combustion in a ground based short duration test facility(combustion driven shock-tunnel), which in addition to flight Mach number can simulate flight Reynolds number as well. In this study a simple method of injection i.e. wall injection of the fuel into the combustion chamber is used. The work starts with threedimensional numerical simulation of a non-reacting gas(air) injection into a hypersonic cross-flow of air to determine the conditions in which air penetrates reasonably well into the cross-flow. Care is taken so that the process does not induce huge pressure loss due to the bow shock which appears in front of the jet column. The code is developed in-house and parallelized using OpenMp model. This is followed by experiments on air injection into a hypersonic cross-flow of air in a conventional shock-tunnel HST2 existing in IISc. The most tricky part is synchronization of injection with start of test-flow in such a short duration(test time 1 millisecond) facility. Next part focuses on numerical simulations to determine the free-stream conditions, mainly the temperature and pressure of air, so that combustion takes place when hydrogen is injected into a supersonic cross-flow of air. The simulations are two-dimensional and includes species conservation equations and source terms due to chemical reactions in addition to the Navier-Stokes equations. This code is also built in-house and parallelized because of more number of operations with the inclusion of species conservation equations and chemical non-equilibrium. However, the predicted conditions were not achievable by HST2 due to low stagnation conditions of HST2. Therefore, a new shock-tunnel which could produce the required conditions is built. The new tunnel is a combustion driven shock-tunnel in which the driver gas is at higher temperature than conventional shock-tunnel. The driver gas is basically a mixture of hydrogen, oxygen and helium at a mole ratio of 2:1:10 initially. The mixture is ignited by spark plugs and the hydrogen and oxygen reacts releasing heat. The heat released raises the temperature of the mixture which is now predominantly helium and small fractions of water vapour and some radicals. The composition of the driver gas and initial pressure are determined through numerical simulations. Experiments follow in the new tunnel on hydrogen injection into a region of supersonic cross-flow between two parallel plates with a wedge attached to the bottom plate. The wedge reduces the hypersonic free-stream to Mach 2. A high-speed camera monitors the flow domain around injection point and sharp rise in luminosity is observed. To ascertain whether the luminosity is due to combustion or not, two more driven gases namely nitrogen and oxygen-rich air are used and the luminosity is compared. In the first case, the free-stream contains no oxygen and luminosity is not observed whereas in the second case higher luminosity than air driver case is visible. Additionally heat-transfer rates are measured at the downstream end of the model and at a height midway between the plates. Similar trend is observed in the relative heat-transfer rates. Wall static pressure at a location downstream of injection port is also measured and compared with numerical simulations. Results of numerical simulations which are carried out at the same conditions as of experiments confirm combustion at supersonic speed. Experiments and numerical simulations show presence of supersonic combustion in the setup. However, further study is necessary to optimize the parameters so that thrust force could be generated efficiently.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Sept. 17, 2009). Includes bibliographical references.