The role of Peroxiredoxin Asp f3 in redox homeostasis and virulence of the human fungal pathogen Aspergillus fumigatus

The incidence of human fungal infections has strongly increased over the last years and Aspergillus fumigatus causes approximately 80 % of all cases in often fatal invasive aspergillosis. A. fumigatus is a ubiquitous ascomycete with a generally saprophytic lifestyle but is also known as an opportunistic human pathogen for immunocompromised individuals. Options for diagnosis and treatment are limited and decline further due to antimycotic resistances. Thus, development of better diagnostic methods as well as the discovery and development of new antifungal treatment options are urgently required. To successfully establish an infection, the fungus must adapt its metabolism to the environment of its human host. This includes adaptation to general conditions like low oxygen or iron deficiency and protection against active innate immune defence mechanisms. The aim of this thesis was to elucidate the functional role of peroxiredoxin Asp f3 in virulence and how it is involved in sensing and detoxification of ROS-associated stress in A. fumigatus. Asp f3 is a two-cysteine type peroxiredoxin that was first identified as a major allergen of A. fumigatus and later as a virulence determinant in a murine model of pulmonary aspergillosis. Here I show that the loss of Asp f3 leads to a shift in the transcriptome upon challenge with reactive oxygen species. Amongst the affected genes are several of putative Afyap1 target genes and subsequently is was shown that Afyap1 fails to sufficiently accumulate in the nucleus to activate ROS-detoxification mechanisms in the Asp f3 deficient background. However, loss of virulence is not caused by insufficient Afyap1 activation, but more likely linked to the fungus ability to grow under low iron conditions or loss thereof in the asp f3 deficient strain and iron supplementation even leads to a full restoration of virulence in a murine infection model

Alcohol Fuel Cells at Optimal Temperatures

High-power-density alcohol fuel cells can relieve many of the daunting challenges facing a hydrogen energy economy. Here, such fuel cells are achieved using CsH2PO4 as the electrolyte and integrating into the anode chamber a Cu-ZnO/Al2O3 methanol steam-reforming catalyst. The temperature of operation, ~250°C, is matched both to the optimal value for fuel cell power output and for reforming. Peak power densities using methanol and ethanol were 226 and 100 mW/cm^2, respectively. The high power output (305 mW/cm^2) obtained from reformate fuel containing 1% CO demonstrates the potential of this approach with optimized reforming catalysts and also the tolerance to CO poisoning at these elevated temperatures

Polymer solid acid composite membranes for fuel-cell applications

A systematic study of the conductivity of polyvinylidene fluoride (PVDF) and CsHSO4 composites, containing 0 to 100% CsHSO4, has been carried out. The polymer, with its good mechanical properties, served as a supporting matrix for the high proton conductivity inorganic phase. The conductivity of composites exhibited a sharp increase with temperature at 142°C, characteristic of the superprotonic phase transition of CsHSO4. At high temperature (160°C), the dependence of conductivity on vol % CsHSO4 was monotonic and revealed a percolation threshold of ~10 vol %. At low temperature (100°C), a maximum in the conductivity at ~80 vol % CsHSO4 was observed. Results of preliminary fuel cell measurements are presented

Solid acid proton conductors: from laboratory curiosities to fuel cell electrolytes

The compound CsH2PO4 has emerged as a viable electrolyte for intermediate temperature (200–300 °C) fuel cells. In order to settle the question of the high temperature behavior of this material, conductivity measurements were performed by two-point AC impedance spectroscopy under humidified conditions (p[H2O] = 0.4 atm). A transition to a stable, high conductivity phase was observed at 230 °C, with the conductivity rising to a value of 2.2 × 10^–2 S cm^–1 at 240 °C and the activation energy of proton transport dropping to 0.42 eV. In the absence of active humidification, dehydration of CsH2PO4 does indeed occur, but, in contradiction to some suggestions in the literature, the dehydration process is not responsible for the high conductivity at this temperature. Electrochemical characterization by galvanostatic current interrupt (GCI) methods and three-point AC impedance spectroscopy (under uniform, humidified gases) of CsH2PO4 based fuel cells, in which a composite mixture of the electrolyte, Pt supported on carbon, Pt black and carbon black served as the electrodes, showed that the overpotential for hydrogen electrooxidation was virtually immeasurable. The overpotential for oxygen electroreduction, however, was found to be on the order of 100 mV at 100 mA cm^–2. Thus, for fuel cells in which the supported electrolyte membrane was only 25 µm in thickness and in which a peak power density of 415 mW cm^–2 was achieved, the majority of the overpotential was found to be due to the slow rate of oxygen electrocatalysis. While the much faster kinetics at the anode over those at the cathode are not surprising, the result indicates that enhancing power output beyond the present levels will require improving cathode properties rather than further lowering the electrolyte thickness. In addition to the characterization of the transport and electrochemical properties of CsH2PO4, a discussion of the entropy of the superprotonic transition and the implications for proton transport is presented

Comprehension of Functional Support by Enculturated Chimpanzees Pan troglodytes

Studies of causal understanding of tool relationships in captive chimpanzees have yielded disparate findings, particularly those reported by Povinelli & colleagues (2000) for tool tasks by laboratory chimpanzees. The present set of experiments tested nine enculturated chimpanzees on three versions of a support task, as described by Povinelli (2000), during which food rewards were presented in different experimental configurations. In Experiment 1, stimulus pairs included a choice between a cloth with a reward on the upper right corner or with a second reward off the cloth, adjacent to a corner, with the second pair comprised of a cloth with food on the upper right corner, and a second cloth with the reward on the substrate, partially covered. All subjects were successful with both test conditions in Experiment 1. In a second study, the experimental choices included one of two possible correct options, paired with one of three incorrect options, with the three incorrect choices all involving varying degrees of perceptual containment. All nine chimpanzees scored significantly above chance across all six conditions. In Experiment 3, four unique conditions were presented, combining one of two possible correct choices with one of two incorrect choices. Six of the subjects scored significantly above chance across the four conditions, and group performance on individual conditions was also significant. Superior performance was demonstrated by female subjects in Experiment 3, similar to sex differences in tool use previously reported for wild chimpanzees and some tool tasks in captive chimpanzees. The present results for Experiments 2 & 3 were significantly differed from those reported by Povinelli et al. (2000) for laboratory-born, peer-reared chimpanzees. One contribution towards the dramatic differences between the two study populations may be the significant rearing and housing differences of the chimpanzee groups. One explanation is that under conditions of enculturation, rich social interactions with humans and conspecifics, as well as active exploration of artifacts, materials, and other aspects of their physical environment had a significant impact on the animals’ ability to recognize the support relationships among the stimulus choices. Overall, the present findings provide strong support for the hypothesis that our chimpanzee subjects based their responses on an understanding of functional support which represented one facet of their folk physics repertoire

Capuchins (Cebus apella) Can Solve a Means-End Problem

Three capuchin monkeys (Cebus apella) were tested on a 2-choice discrimination task designed to examine their knowledge of support, modeled after Hauser, Kralik, and Botto-Mahan’s (1999) experiments with tamarins. This task involved a choice between 2 pieces of cloth, including 1 with a food reward placed on its surface, and a second cloth with the food reward next to its surface. After reliably solving the basic problem, the capuchins were tested with various alternations of the original food reward and cloth. The capuchins were able to solve the initial task quickly, and generalize their knowledge to additional functional and nonfunctional variations of the problem. In comparison to the tamarins previously tested on this problem (Hauser et al., 1999), the capuchins were able to reach criterion faster during the training and food size conditions and showed a greater ability to inhibit reaching toward larger food rewards that were unavailable

Wave-vector dependent intensity variations of the Kondo peak in photoemission from CePd3_3

Strong angle-dependent intensity variations of the Fermi-level feature are observed in 4d - 4f resonant photoemission spectra of CePd$_3$(111), that reveal the periodicity of the lattice and largest intensity close to the Gamma points of the surface Brillouin zone. In the framework of a simplified periodic Anderson model the phenomena may quantitatively be described by a wave-vector dependence of the electron hopping matrix elements caused by Fermi-level crossings of non-4f-derived energy bands

Proton conducting membrane using a solid acid

A solid acid material is used as a proton conducting membrane in an electrochemical device. The solid acid material can be one of a plurality of different kinds of materials. A binder can be added, and that binder can be either a nonconducting or a conducting binder. Nonconducting binders can be, for example, a polymer or a glass. A conducting binder enables the device to be both proton conducting and electron conducting. The solid acid material has the general form M.sub.a H.sub.b (XO.sub.t).sub.c