Decentralized interaction and co-adaptation in the repeated prisoner's dilemma

The purpose of this paper is to propose a nonparametric interest rate term structure model and investigate its implications on term structure dynamics and prices of interest rate derivative securities. The nonparametric spot interest rate process is estimated from the observed short-term interest rates following a robust estimation procedure and the market price of interest rate risk is estimated as implied from the historical term structure data. That is, instead of imposing a priori restrictions on the model, data are allowed to speak for themselves, and at the same time the model retains a parsimonious structure and the computational tractability. The model is implemented using historical Canadian interest rate term structure data. The parametric models with closed form solutions for bond and bond option prices, namely the Vasicek (1977) and CIR (1985) models, are also estimated for comparison purpose. The empirical results not only provide strong evidence that the traditional spot interest rate models and market prices of interest rate risk are severely misspecified but also suggest that different model specifications have significant impact on term structure dynamics and prices of interest rate derivative securities.

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate).

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies

Topological lattice using multi-frequency radiation

We describe a novel technique for creating an artificial magnetic field for ultra-cold atoms using a periodically pulsed pair of counter propagating Raman lasers that drive transitions between a pair of internal atomic spin states: a multi-frequency coupling term. In conjunction with a magnetic field gradient, this dynamically generates a rectangular lattice with a non-staggered magnetic flux. For a wide range of parameters, the resulting Bloch bands have non-trivial topology, reminiscent of Landau levels, as quantified by their Chern numbers.Comment: Replaced with a revised version, 15 pages, 6 figure

Merit Motives and Government Intervention: Public Finance in Reverse

A common view in public finance is that there is an efficiency-redistribution tradeoff in which distortions are tolerated in order to redistribute income. However, the fact that so much public- and private redistributive activity involves in-kind transfers rather than cash may be indicative of merit motives on the part of the payers rather than a preference for the well-being of the recipients. Efficiency-enhancing public policy in a merit good economy has the primary purpose of creating distortions and may only redistribute income from rich to poor in order to create those distortions the reverse of the conventional efficiency-redistribution tradeoff. We discuss why the largest programs on the federal and local level in the US including Social Security, Medicare and Medicaid, and Public Schooling seem consistent with the reverse tradeoff rather than the classic one. Transfers are not lump sum in a merit good economy, and explicitly accounting for this when calculating tax incidence reduces the estimated progressivity of government policy. As one example, we calibrate the conventional life-cycle model to show how the amount of over-saving induced on the poor by Social Security hurts them at least as much as the progressive' benefits help them. When the distortions outweigh fiscal transfers in this manner, the classic efficiency-redistribution tradeoff cannot justify the program and the program is far less progressive than conventional analysis suggests.

Who Benefits from New Medical Technologies? Estimates of Consumer and Producer Surpluses for HIV/AIDS Drugs

The social value of an innovation is comprised of the value to consumers and the value to innovators. We estimate that for the HIV/AIDS therapies that entered the market from the late 1980's onwards, innovators appropriated only 5% of the social surplus arising from these new technologies. Despite the high annual costs of these drugs to patients, the low share of social surplus going to innovators raises concerns about advocating cost-effectiveness criteria that would further reduce this share, and hence further reduce incentives for innovation.

Surplus Appropriation from R&D and Health Care Technology Assessment Procedures

Given the rapid growth in health care spending that is often attributed to technological change, many private and public institutions are grappling with how to best assess and adopt new health care technologies. The leading technology adoption criteria proposed in theory and used in practice involve so called "cost-effectiveness" measures. However, little is known about the dynamic efficiency implications of such criteria, in particular how they influence the R&D investments that make technologies available in the first place. We argue that such criteria implicitly concern maximizing consumer surplus, which many times is consistent with maximizing static efficiency after an innovation has been developed. Dynamic efficiency, however, concerns aligning the social costs and benefits of R&D and is therefore determined by how much of the social surplus from the new technology is appropriated as producer surplus. We analyze the relationship between cost-effectiveness measures and the degree of surplus appropriation by innovators driving dynamic efficiency. We illustrate how to estimate the two for the new HIV/AIDS therapies that entered the market after the late 1980's and find that only 5% of the social surplus is appropriated by innovators. We show how this finding can be generalized to other existing cost-effectiveness estimates by deriving how those estimates identify innovator appropriation for a set of studies of over 200 drugs. We find that these studies implicitly support a low degree of appropriation as well. Despite the high annual cost of drugs to patients, very low shares of social surplus may go to innovators, which may imply that cost-effectiveness is too high in a dynamic efficiency sense.

Structural and mechanistic insights into pore formation by proteins of the membrane attack complex/perforin superfamily

Members of the membrane attack complex/perforin (MACPF) superfamily of pore-forming proteins are characterised by a common three-dimensional fold able to puncture lipid membranes. They are found in bacterial and eukaryotes, and include immune effectors, toxins and pathogenic virulence factors. Their conserved pore-forming domain follows the same mechanism whereby two bundles of α-helices unfurl into membrane-spanning β-hairpins. This thesis provides insights into the effects of MACPF proteins on biological membranes. Coarse-grain molecular dynamics simulations of the membrane attack complex (MAC) bound to its inhibitor CD59 reveal protein-lipid interactions and local changes in membrane thickness. These may serve as signals to recruit CD59 or the molecular machinery for MAC clearance. Some bacterial MACPF proteins called cholesterol-dependent cytolysins (CDCs) hijack CD59 on human cells as part of their pore formation pathway. Atomistic simulations of CD59 in a lipid bilayer show that it samples various orientations relative to the membrane, dictating whether its binding site is available for engaging MAC or CDCs, and thus for inhibiting or promoting pore formation. CDCs assemble on cholesterol-rich lipid membranes and undergo sequential conformational changes to puncture bilayers. Site-directed mutagenesis of two CDCs reveals that an amphipathic helix in the pore-forming helical bundles is responsible for tuning the lytic activity of these proteins. Understanding the molecular basis for the function of this helix will require the high-resolution structure of a CDC late prepore intermediate. The first steps towards solving this structure by cryo-electron microscopy are presented in this thesis.Open Acces