Intranasal administration of the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei with the modified heat-labile toxin of Escherichia coli (LTK63) induces a complete protection against malaria challenge.

Needle-free procedures are very attractive ways to deliver vaccines because they diminish the risk of contamination and may reduce local reactions, pain or pain fear especially in young children with a consequence of increasing the vaccination coverage for the whole population. For this purpose, the possible development of a mucosal malaria vaccine was investigated. Intranasal immunization was performed in BALB/c mice using a well-studied Plasmodium berghei model antigen derived from the circumsporozoite protein with the modified heat-labile toxin of Escherichia coli (LTK63), which is devoid of any enzymatic activity compared to the wild type form. Here, we show that intranasal administration of the two compounds activates the T and B cell immune response locally and systemically. In addition, a total protection of mice is obtained upon a challenge with live sporozoites.

Three essays in financial economics: asset pricing, optimal portfolio selection and financial integration

Executive Summary The unifying theme of this thesis is the pursuit of a satisfactory ways to quantify the riskureward trade-off in financial economics. First in the context of a general asset pricing model, then across models and finally across country borders. The guiding principle in that pursuit was to seek innovative solutions by combining ideas from different fields in economics and broad scientific research. For example, in the first part of this thesis we sought a fruitful application of strong existence results in utility theory to topics in asset pricing. In the second part we implement an idea from the field of fuzzy set theory to the optimal portfolio selection problem, while the third part of this thesis is to the best of our knowledge, the first empirical application of some general results in asset pricing in incomplete markets to the important topic of measurement of financial integration. While the first two parts of this thesis effectively combine well-known ways to quantify the risk-reward trade-offs the third one can be viewed as an empirical verification of the usefulness of the so-called "good deal bounds" theory in designing risk-sensitive pricing bounds. Chapter 1 develops a discrete-time asset pricing model, based on a novel ordinally equivalent representation of recursive utility. To the best of our knowledge, we are the first to use a member of a novel class of recursive utility generators to construct a representative agent model to address some long-lasting issues in asset pricing. Applying strong representation results allows us to show that the model features countercyclical risk premia, for both consumption and financial risk, together with low and procyclical risk free rate. As the recursive utility used nests as a special case the well-known time-state separable utility, all results nest the corresponding ones from the standard model and thus shed light on its well-known shortcomings. The empirical investigation to support these theoretical results, however, showed that as long as one resorts to econometric methods based on approximating conditional moments with unconditional ones, it is not possible to distinguish the model we propose from the standard one. Chapter 2 is a join work with Sergei Sontchik. There we provide theoretical and empirical motivation for aggregation of performance measures. The main idea is that as it makes sense to apply several performance measures ex-post, it also makes sense to base optimal portfolio selection on ex-ante maximization of as many possible performance measures as desired. We thus offer a concrete algorithm for optimal portfolio selection via ex-ante optimization over different horizons of several risk-return trade-offs simultaneously. An empirical application of that algorithm, using seven popular performance measures, suggests that realized returns feature better distributional characteristics relative to those of realized returns from portfolio strategies optimal with respect to single performance measures. When comparing the distributions of realized returns we used two partial risk-reward orderings first and second order stochastic dominance. We first used the Kolmogorov Smirnov test to determine if the two distributions are indeed different, which combined with a visual inspection allowed us to demonstrate that the way we propose to aggregate performance measures leads to portfolio realized returns that first order stochastically dominate the ones that result from optimization only with respect to, for example, Treynor ratio and Jensen's alpha. We checked for second order stochastic dominance via point wise comparison of the so-called absolute Lorenz curve, or the sequence of expected shortfalls for a range of quantiles. As soon as the plot of the absolute Lorenz curve for the aggregated performance measures was above the one corresponding to each individual measure, we were tempted to conclude that the algorithm we propose leads to portfolio returns distribution that second order stochastically dominates virtually all performance measures considered. Chapter 3 proposes a measure of financial integration, based on recent advances in asset pricing in incomplete markets. Given a base market (a set of traded assets) and an index of another market, we propose to measure financial integration through time by the size of the spread between the pricing bounds of the market index, relative to the base market. The bigger the spread around country index A, viewed from market B, the less integrated markets A and B are. We investigate the presence of structural breaks in the size of the spread for EMU member country indices before and after the introduction of the Euro. We find evidence that both the level and the volatility of our financial integration measure increased after the introduction of the Euro. That counterintuitive result suggests the presence of an inherent weakness in the attempt to measure financial integration independently of economic fundamentals. Nevertheless, the results about the bounds on the risk free rate appear plausible from the view point of existing economic theory about the impact of integration on interest rates.

Three essays in risk management in financial institutions

The choice to adopt risk-sensitive measurement approaches for operational risks: the case of Advanced Measurement Approach under Basel II New Capital Accord This paper investigates the choice of the operational risk approach under Basel II requirements and whether the adoption of advanced risk measurement approaches allows banks to save capital. Among the three possible approaches for operational risk measurement, the Advanced Measurement Approach (AMA) is the most sophisticated and requires the use of historical loss data, the application of statistical tools, and the engagement of a highly qualified staff. Our results provide evidence that the adoption of AMA is contingent on the availability of bank resources and prior experience in risk-sensitive operational risk measurement practices. Moreover, banks that choose AMA exhibit low requirements for capital and, as a result might gain a competitive advantage compared to banks that opt for less sophisticated approaches. - Internal Risk Controls and their Impact on Bank Solvency Recent cases in financial sector showed the importance of risk management controls on risk taking and firm performance. Despite advances in the design and implementation of risk management mechanisms, there is little research on their impact on behavior and performance of firms. Based on data from a sample of 88 banks covering the period between 2004 and 2010, we provide evidence that internal risk controls impact the solvency of banks. In addition, our results show that the level of internal risk controls leads to a higher degree of solvency in banks with a major shareholder in contrast to widely-held banks. However, the relationship between internal risk controls and bank solvency is negatively affected by BHC growth strategies and external restrictions on bank activities, while the higher regulatory requirements for bank capital moderates positively this relationship. - The Impact of the Sophistication of Risk Measurement Approaches under Basel II on Bank Holding Companies Value Previous research showed the importance of external regulation on banks' behavior. Some inefficient standards may accentuate risk-taking in banks and provoke a financial crisis. Despite the growing literature on the potential effects of Basel II rules, there is little empirical research on the efficiency of risk-sensitive capital measurement approaches and their impact on bank profitability and market valuation. Based on data from a sample of 66 banks covering the period between 2008 and 2010, we provide evidence that prudential ratios computed under Basel II standards predict the value of banks. However, this relation is contingent on the degree of sophistication of risk measurement approaches that banks apply. Capital ratios are effective in predicting bank market valuation when banks adopt the advanced approaches to compute the value of their risk-weighted assets.

Audit report on Internal Control over Financial Reporting of the State University of Iowa as of and for the year ended June 30, 2011

Audit report on Internal Control over Financial Reporting of the State University of Iowa as of and for the year ended June 30, 2011

Independent auditor’s report of the State of Iowa on internal control over financial reporting and on compliance and other matters based on an audit of financial statements performed in accordance with government auditing standards for the year ended June 30, 2011

Independent auditor’s report of the State of Iowa on internal control over financial reporting and on compliance and other matters based on an audit of financial statements performed in accordance with government auditing standards for the year ended June 30, 2011

Jackson County Sanitary Disposal Agency independent auditor's reports, basic financial statements and required supplementary information, schedule of findings, June 30, 2011

Audit report on the Jackson County Sanitary Disposal Agency for the year ended June 30, 2011

Bacterial-induced protection against allergy through a novel multi-component immunoregulatory mechanism

Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. We have found that pulmonary exposure with the bacterium Escherichia coli leads to a suppression of allergic airway inflammation, characterized by reduced airway-hyperresponsiveness, eosinophilia and cytokine production by T cells in the lung. This immune modulation was neither mediated by the induction of a Th1 response nor regulatory T cells; was dependent on TLR-4 but did not involve TLR-desensitization. Dendritic cell migration to the draining lymph nodes and subsequent activation of T cells was unaffected by prior exposure to E.coli indicating that the immunomodulation was limited to the lung environment. In non-treated control mice ovalbumin was primarily presented by airway CD11b+ CD11c+ DCs expressing high levels of MHC class II molecules whilst the DCs in E.coli-treated mice displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production by ovalbuminspecific effector T cells recruited to the airways was significantly reduced. The suppression of airways hyper responsiveness was mediated through the recruitment of IL-17-producing gd-T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of TNF-alpha. Taken together, these data reveal a novel multi-component immunoregulatory pathway that acts to protect the airways from allergic inflammation.

Comparison of protection methods of pine stacks against Tomicus piniperda

Summary

Ultraviolet damage to the eye revisited: eye-sun protection factor (E-SPF®), a new ultraviolet protection label for eyewear.

Ultraviolet (UV) radiation potentially damages the skin, the immune system, and structures of the eye. A useful UV sun protection for the skin has been established. Since a remarkable body of evidence shows an association between UV radiation and damage to structures of the eye, eye protection is important, but a reliable and practical tool to assess and compare the UV-protective properties of lenses has been lacking. Among the general lay public, misconceptions on eye-sun protection have been identified. For example, sun protection is mainly ascribed to sunglasses, but less so to clear lenses. Skin malignancies in the periorbital region are frequent, but usual topical skin protection does not include the lids. Recent research utilized exact dosimetry and demonstrated relevant differences in UV burden to the eye and skin at a given ambient irradiation. Chronic UV effects on the cornea and lens are cumulative, so effective UV protection of the eyes is important for all age groups and should be used systematically. Protection of children's eyes is especially important, because UV transmittance is higher at a very young age, allowing higher levels of UV radiation to reach the crystalline lens and even the retina. Sunglasses as well as clear lenses (plano and prescription) effectively reduce transmittance of UV radiation. However, an important share of the UV burden to the eye is explained by back reflection of radiation from lenses to the eye. UV radiation incident from an angle of 135°-150° behind a lens wearer is reflected from the back side of lenses. The usual antireflective coatings considerably increase reflection of UV radiation. To provide reliable labeling of the protective potential of lenses, an eye-sun protection factor (E-SPF®) has been developed. It integrates UV transmission as well as UV reflectance of lenses. The E-SPF® compares well with established skin-sun protection factors and provides clear messages to eye health care providers and to lay consumers.

Involvement of 4E-BP1 in the protection induced by HDLs on pancreatic beta cells.

High-density lipoproteins (HDLs) protect pancreatic beta cells against apoptosis. This property might relate to the increased risk to develop diabetes in patients with low HDL blood levels. The mechanisms by which HDLs protect beta cells are poorly characterized however. Here we used a transcriptomic approach to identify genes differentially modulated by HDLs in beta cells subjected to apoptotic stimuli. The transcript encoding 4E-BP1 was up-regulated by serum starvation and HDLs blocked this increase. 4E-BP1 inhibits cap-dependent translation in its non- or hypo-phosphorylated state but it looses this ability when hyper-phosphorylated. At the protein level, 4E-BP1 was also up-regulated in response to starvation and IL1beta and this was blunted by HDLs. While an ectopic increase of 4E-BP1 expression induced beta cell death, silencing 4E-BP1 increase with shRNAs inhibited the apoptotic-inducing capacities of starvation. HDLs can therefore protect beta cells by blocking 4E-BP1 protein expression but this is not the sole protective mechanism activated by HDLs. Indeed, HDLs blocked apoptosis induced by ER stress with no associated decrease in total 4E-BP1 induction. Although, HDLs favored the phosphorylation, and hence the inactivation of 4E-BP1 in these conditions, this appeared not to be required for HDL protection. Our results indicate that HDLs can protect beta cells through modulation of 4E-BP1 depending on the type of stress stimuli.

Continuous-time random-walk model for financial distributions

We apply the formalism of the continuous-time random walk to the study of financial data. The entire distribution of prices can be obtained once two auxiliary densities are known. These are the probability densities for the pausing time between successive jumps and the corresponding probability density for the magnitude of a jump. We have applied the formalism to data on the U.S. dollardeutsche mark future exchange, finding good agreement between theory and the observed data.