Modelling the dynamic response of rockfall protection barriers

Mountainous areas are prone to natural hazards like rockfalls. Among the many countermeasures, rockfall protection barriers represent an effective solution to mitigate the risk. They are metallic structures designed to intercept rocks falling from unstable slopes, thus dissipating the energy deriving from the impact. This study aims at providing a better understanding of the response of several rockfall barrier types, through the development of rather sophisticated three-dimensional numerical finite elements models which take into account for the highly dynamic and non-linear conditions of such events. The models are built considering the actual geometrical and mechanical properties of real systems. Particular attention is given to the connecting details between the structural components and to their interactions. The importance of the work lies in being able to support a wide experimental activity with appropriate numerical modelling. The data of several full-scale tests carried out on barrier prototypes, as well as on their structural components, are combined with results of numerical simulations. Though the models are designed with relatively simple solutions in order to obtain a low computational cost of the simulations, they are able to reproduce with great accuracy the test results, thus validating the reliability of the numerical strategy proposed for the design of these structures. The developed models have shown to be readily applied to predict the barrier performance under different possible scenarios, by varying the initial configuration of the structures and/or of the impact conditions. Furthermore, the numerical models enable to optimize the design of these structures and to evaluate the benefit of possible solutions. Finally it is shown they can be also used as a valuable supporting tool for the operators within a rockfall risk assessment procedure, to gain crucial understanding of the performance of existing barriers in working conditions.

Modelling biogeochemical cycles in forest ecosystems: a Bayesian approach

Forest models are tools for explaining and predicting the dynamics of forest ecosystems. They simulate forest behavior by integrating information on the underlying processes in trees, soil and atmosphere. Bayesian calibration is the application of probability theory to parameter estimation. It is a method, applicable to all models, that quantifies output uncertainty and identifies key parameters and variables. This study aims at testing the Bayesian procedure for calibration to different types of forest models, to evaluate their performances and the uncertainties associated with them. In particular,we aimed at 1) applying a Bayesian framework to calibrate forest models and test their performances in different biomes and different environmental conditions, 2) identifying and solve structure-related issues in simple models, and 3) identifying the advantages of additional information made available when calibrating forest models with a Bayesian approach. We applied the Bayesian framework to calibrate the Prelued model on eight Italian eddy-covariance sites in Chapter 2. The ability of Prelued to reproduce the estimated Gross Primary Productivity (GPP) was tested over contrasting natural vegetation types that represented a wide range of climatic and environmental conditions. The issues related to Prelued's multiplicative structure were the main topic of Chapter 3: several different MCMC-based procedures were applied within a Bayesian framework to calibrate the model, and their performances were compared. A more complex model was applied in Chapter 4, focusing on the application of the physiology-based model HYDRALL to the forest ecosystem of Lavarone (IT) to evaluate the importance of additional information in the calibration procedure and their impact on model performances, model uncertainties, and parameter estimation. Overall, the Bayesian technique proved to be an excellent and versatile tool to successfully calibrate forest models of different structure and complexity, on different kind and number of variables and with a different number of parameters involved.

Host race formation in Hyalesthes obsoletus (Signoret 1865)

Die Winden-Glasflügelzikade Hyalesthes obsoletus (Cixiidae, Glasflügelzikaden) nutzte in Deutschland ursprünglich die Ackerwinde Convolvulus arvensis als Wirtspflanze, allerdings nahm in den letzten zwei Dekaden die Abundanz auf der Großen Brennnessel Urtica dioica stark zu, zusammen mit der Inzidenz der Schwarzholzkrankheit Bois noir auf Weinreben. Bois noir wird durch ein Phytoplasma verursacht, das durch H. obsoletus von C. arvensis und U. dioica auf Weinreben übertragen wird. Es stellte sich daher die Frage, ob H. obsoletus Wirtsrassen entwickelt hat, die möglicherweise die Bois noir-Epidemiologie beeinflussen. In der vorliegenden Studie wurden folgende Fragestellungen bearbeitet: rn(1) Gibt es in Deutschland und Europa genetisch unterscheidbare Wirtsrassen von H. obsoletus auf den beiden Wirtspflanzen C. arvensis und U. dioica? Es wurden sieben Mikrosatellitenmarker entwickelt und etabliert, um H. obsoletus Populationen aus Deutschland und Europa genetisch zu analysieren. Es zeigte sich eine deutliche Differenzierung zwischen Populationen von beiden Wirtspflanzen in Deutschland, jedoch nicht in den historischen Ursprungsgebieten der deutschen Populationen, in der Schweiz, Italien oder Slovenien.rn(2) Wo sind die deutschen Wirtsrassen von H. obsoletus entstanden? Eine Einwanderung von südlichen, bereits an U. dioica angepassten Individuen stand einer lokalen Wirtsrassenevolution gegenüber. Die engere genetische Verwandtschaft der deutschen Population auf U. dioica zu denen auf C. arvensis, im Vergleich zu den übrigen Populationen auf U. dioica, impliziert einen lokalen Prozess im nördlichen Verbreitungsgebiet. Eine Immigration südlicher Tiere scheint nicht zur Diversifizierung beigetragen zu haben, führte aber möglicherweise einen U. dioica-spezifischen Phytoplasma-Stamm ein. Durch Wirtsrassenevolution entwickelten sich spezifische, vektorbasierte epidemiologische Kreisläufe der Schwarzholzkrankheit Bois noir. rn(3) Welche Präferenzen zeigen die beiden Wirtsrassen von H. obsoletus für die Wirtspflanzen C. arvensis und U. dioica und unterscheiden sich diese? Die Präferenz von H. obsoletus aus beiden deutschen Wirtsrassen in Bezug auf den Geruch der Wirtspflanzen wurde in einem Y-Olfaktometer untersucht, zusätzlich wurden beide Pflanzen direkt zur Wahl gestellt. Bei beiden Untersuchungen zeigte die Population von C. arvensis eine signifikante Präferenz für ihre native Wirtspflanze. Die Population von U. dioica wies dagegen keine Präferenz für den Geruch einer Wirtspflanze auf, bevorzugte im direkten Test jedoch signifikant ihre native Wirtspflanze. Dies weist darauf hin, dass die Anpassung an den „neuen“ Wirt noch nicht vollständig ist.rn

Modelling, simulation and optimization of maintenance considerations on condition based maintenance

Globalization has increased the pressure on organizations and companies to operate in the most efficient and economic way. This tendency promotes that companies concentrate more and more on their core businesses, outsource less profitable departments and services to reduce costs. By contrast to earlier times, companies are highly specialized and have a low real net output ratio. For being able to provide the consumers with the right products, those companies have to collaborate with other suppliers and form large supply chains. An effect of large supply chains is the deficiency of high stocks and stockholding costs. This fact has lead to the rapid spread of Just-in-Time logistic concepts aimed minimizing stock by simultaneous high availability of products. Those concurring goals, minimizing stock by simultaneous high product availability, claim for high availability of the production systems in the way that an incoming order can immediately processed. Besides of design aspects and the quality of the production system, maintenance has a strong impact on production system availability. In the last decades, there has been many attempts to create maintenance models for availability optimization. Most of them concentrated on the availability aspect only without incorporating further aspects as logistics and profitability of the overall system. However, production system operator’s main intention is to optimize the profitability of the production system and not the availability of the production system. Thus, classic models, limited to represent and optimize maintenance strategies under the light of availability, fail. A novel approach, incorporating all financial impacting processes of and around a production system, is needed. The proposed model is subdivided into three parts, maintenance module, production module and connection module. This subdivision provides easy maintainability and simple extendability. Within those modules, all aspect of production process are modeled. Main part of the work lies in the extended maintenance and failure module that offers a representation of different maintenance strategies but also incorporates the effect of over-maintaining and failed maintenance (maintenance induced failures). Order release and seizing of the production system are modeled in the production part. Due to computational power limitation, it was not possible to run the simulation and the optimization with the fully developed production model. Thus, the production model was reduced to a black-box without higher degree of details.

Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis

Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG(1) was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG(3) was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC- and isothermal titration calorimetry-based assays followed by Hill plots, revealed non-Michaelis-Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG(1) cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin-dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance.

Development of a model-based transient calibration process for diesel engine electronic control module tables – Part 2: modelling and optimization

This is the second part of a study investigating a model-based transient calibration process for diesel engines. The first part addressed the data requirements and data processing required for empirical transient emission and torque models. The current work focuses on modelling and optimization. The unexpected result of this investigation is that when trained on transient data, simple regression models perform better than more powerful methods such as neural networks or localized regression. This result has been attributed to extrapolation over data that have estimated rather than measured transient air-handling parameters. The challenges of detecting and preventing extrapolation using statistical methods that work well with steady-state data have been explained. The concept of constraining the distribution of statistical leverage relative to the distribution of the starting solution to prevent extrapolation during the optimization process has been proposed and demonstrated. Separate from the issue of extrapolation is preventing the search from being quasi-static. Second-order linear dynamic constraint models have been proposed to prevent the search from returning solutions that are feasible if each point were run at steady state, but which are unrealistic in a transient sense. Dynamic constraint models translate commanded parameters to actually achieved parameters that then feed into the transient emission and torque models. Combined model inaccuracies have been used to adjust the optimized solutions. To frame the optimization problem within reasonable dimensionality, the coefficients of commanded surfaces that approximate engine tables are adjusted during search iterations, each of which involves simulating the entire transient cycle. The resulting strategy, different from the corresponding manual calibration strategy and resulting in lower emissions and efficiency, is intended to improve rather than replace the manual calibration process.

The function of secretory IgA in the context of the intestinal continuum of adaptive immune responses in host-microbial mutualism

The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into the continuum of intestinal CD4 T cell responses, to achieve a mutualistic relationship between the intestinal commensal microbiota and the host.

Hostile takeover by Plasmodium: reorganization of parasite and host cell membranes during liver stage egress

The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection.

Chronicle of a death foretold: Plasmodium liver stage parasites decide on the fate of the host cell

Protozoan parasites of the genus Plasmodium are the causative agents of malaria. Despite more than 100 years of research, the complex life cycle of the parasite still bears many surprises and it is safe to say that understanding the biology of the pathogen will keep scientists busy for many years to come. Malaria research has mainly concentrated on the pathological blood stage of Plasmodium parasites, leaving us with many questions concerning parasite development within the mosquito and during the exo-erythrocytic stage in the vertebrate host. After the discovery of the Plasmodium liver stage in the middle of the last century, it remained understudied for many years but the realization that it represents a promising target for vaccination approaches has brought it back into focus. The last decade saw many new and exciting discoveries concerning the exo-erythrocytic stage and in this review we will discuss the highlights of the latest developments in the field.

Biogeochemical processes in a clay formation in situ experiment: Part F - Reactive transport modelling

Reactive transport modelling was used to simulate solute transport, thermodynamic reactions, ion exchange and biodegradation in the Porewater Chemistry (PC) experiment at the Mont Terri Rock Laboratory. Simulations show that the most important chemical processes controlling the fluid composition within the borehole and the surrounding formation during the experiment are ion exchange, biodegradation and dissolution/precipitation reactions involving pyrite and carbonate minerals. In contrast, thermodynamic mineral dissolution/precipitation reactions involving alumo-silicate minerals have little impact on the fluid composition on the time-scale of the experiment. With the accurate description of the initial chemical condition in the formation in combination with kinetic formulations describing the different stages of bacterial activities, it has been possible to reproduce the evolution of important system parameters, such as the pH, redox potential, total organic C. dissolved inorganic C and SO(4) concentration. Leaching of glycerol from the pH-electrode may be the primary source of organic material that initiated bacterial growth, which caused the chemical perturbation in the borehole. Results from these simulations are consistent with data from the over-coring and demonstrate that the Opalinus Clay has a high buffering capacity in terms of chemical perturbations caused by bacterial activity. This buffering capacity can be attributed to the carbonate system as well as to the reactivity of clay surfaces.

Identification of a host cell target for the thiazolide class of broad-spectrum anti-parasitic drugs

The thiazolide nitazoxanide (NTZ) and some derivatives exhibit considerable in vitro activities against a broad range of parasites, including the apicomplexans Neospora caninum and Toxoplasma gondii tachyzoites. In order to identify potential molecular targets for this compound in both parasites, RM4847 was coupled to epoxy-agarose and affinity chromatography was performed. A protein of approximately 35 kDa was eluted upon RM4847-affinity-chromatography from extracts of N. caninum-infected human foreskin fibroblasts (HFF) and non-infected HFF, but no protein was eluted when affinity chromatography was performed with T. gondii or N. caninum tachyzoite extracts. Mass spectrometry analysis identified the 35 kDa protein as human quinone reductase NQO1 (P15559; QR). Within 8h after infection of HFF with N. caninum tachyzoites, QR transcript expression levels were notably increased, but no such increase was observed upon infection with T. gondii tachyzoites. Treatment of non-infected HFF with RM4847 did also lead to an increase of QR transcript levels. The enzymatic activity of 6-histidine-tagged recombinant QR (recQR) was assayed using menadione as a substrate. The thiazolides NTZ, tizoxanide and RM4847 inhibited recQR activity on menadione in a concentration-dependent manner. Moreover, a small residual reducing activity was observed when these thiazolides were offered as substrates.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Host cell responses of Salmonella typhimurium infected human dendritic cells

Live attenuated Salmonella are attractive vaccine candidates for mucosal application because they induce both mucosal immune responses and systematic immune responses. After breaking the epithelium barrier, Salmonella typhimurium is found within dendritic cells (DC) in the Peyer's patches. Although there are abundant data on the interaction of S. typhimurium with murine epithelial cells, macrophages and DC, little is known about its interaction with human DC. Live attenuated S. typhimurium have recently been shown to efficiently infect human DC in vitro and induce production of cytokines. In this study, we have analysed the morphological consequences of infection of human DC by the attenuated S. typhimurium mutant strains designated PhoPc, AroA and SipB and the wild-type strains of the American Type Culture Collection (Manassas, VA, USA), ATCC 14028 and ATCC C53, by electron microscopy at 30 min, 3 h and 24 h after exposure. Our results show that genetic background of the strains profoundly influence DC morphology following infection. The changes included (i) membrane ruffling; (ii) formation of tight or spacious phagosomes; (iii) apoptosis; and (iv) spherical, pedunculated membrane-bound microvesicles that project from the plasma membrane. Despite the fact that membrane ruffling was much more pronounced with the two virulent strains, all mutants were taken up by the DC. The microvesicles were induced by all the attenuated strains, including SipB, which did not induce apoptosis in the host cell. These results suggest that Salmonella is internalized by human DC, inducing morphological changes in the DC that could explain immunogenicity of the attenuated strains.

Aeromonas exoenzyme T of Aeromonas salmonicida is a bifunctional protein that targets the host cytoskeleton

Type III protein secretion has been shown recently to be important in the virulence of the fish pathogen Aeromonas salmonicida. The ADP-ribosylating toxin Aeromonas exoenzyme T (AexT) is one effector protein targeted for secretion via this system. In this study, we identified muscular and nonmuscular actin as substrates of the ADP-ribosylating activity of AexT. Furthermore, we show that AexT also functions as a GTPase-activating protein (GAP), displaying GAP activity against monomeric GTPases of the Rho family, specifically Rho, Rac, and Cdc42. Transfection of fish cells with wild type AexT resulted in depolymerization of the actin cytoskeleton and cell rounding. Point mutations within either the GAP or the ADP-ribosylating active sites of AexT (Arg-143 as well as Glu-398 and Glu-401, respectively) abolished enzymatic activity, yet did not prevent actin filament depolymerization. However, inactivation of the two catalytic sites simultaneously did. These results suggest that both the GAP and ADP-ribosylating domains of AexT contribute to its biological activity. This is the first bacterial virulence factor to be described that has a specific actin ADP-ribosylation activity and GAP activity toward Rho, Rac, and Cdc42, both enzymatic activities contributing to actin filament depolymerization.

Modelling the results of health promotion activities in Switzerland: development of the Swiss Model for Outcome Classification in Health Promotion and Prevention

This paper describes the Model for Outcome Classification in Health Promotion and Prevention adopted by Health Promotion Switzerland (SMOC, Swiss Model for Outcome Classification) and the process of its development. The context and method of model development, and the aim and objectives of the model are outlined. Preliminary experience with application of the model in evaluation planning and situation analysis is reported. On the basis of an extensive literature search, the model is situated within the wider international context of similar efforts to meet the challenge of developing tools to assess systematically the activities of health promotion and prevention.