11beta-hydroxysteroid dehydrogenases as regulators of pulmonary corticosterone during the granulomatous response to trehalose 6,6'-dimycolate

Protection against Mycobacterium tuberculosis requires development and maintenance of granulomatous lesions, a feature considered to be the pathological hallmark of Tuberculosis (TB) disease. Upon encountering Mtb or mycobacterial antigens, specifically trehalose 6,6'-dimycolate (TDM), a strong local pro-inflammatory response is initiated. Systemic production of anti-inflammatory glucocorticoids (GCs) is also induced. Emergence of these antagonists at the inflammatory foci is counterproductive to development of the granulomatous structure and detrimental to host protection against TB. Therefore, it was hypothesized that local enzymatic regulation of GCs occurs locally at the site of granulomatous inflammation. The experiments described here strongly suggest that 11β-hydroxysteroid dehydrogenases (11βHSDs) shuttle GCs between active and inert forms during the acute granulomatous response, supporting the net reduction of corticosterone. The patterns of GC and 11βHSD regulation were specific to the lung (the site of inflammation) and were not observed in other tissues. Furthermore, 11βHSD2, which decreases corticosterone concentrations, was not expressed in models of dysregulated granulomatous inflammation. These findings suggest that cellular exposure to local active GC concentrations is restricted via 11βHSDs as a mechanism to initiate and maintain granuloma formation. The information derived from the experiments outlined in this dissertation provides a better understanding of the events required for establishment and maintenance of the protective granulomatous response. As a practical consequence, exploiting 11βHSD2 modulation of GCs at the site of Mtb infection may lead to improvement of Tuberculosis treatment strategies.^

Regulation of Bcl-2 expression by the product of the prostate apoptosis response gene -4, Par-4

Elevated expression levels of the bcl-2 proto-oncogene have been correlated with the appearance of androgen independence in prostate cancer. Although bcl-2 was first cloned as the t (14:18) translocation breakpoint from human follicular B cell lymphoma, the mechanism of overexpression of bcl-2 is largely undefined for advanced prostate cancer, there being no gross alterations in the gene structure. We investigated the role of the product of the prostate apoptosis response gene-4 (Par-4) and the product of the Wilms' tumor 1 gene (WT1) in the regulation of Bcl-2 expression in prostate cancer cell lines. We observed growth arrest and apoptosis, upon decreasing Bcl-2 protein and transcript in the high Bcl-2 expressing, androgen-independent prostate cancer cell lines, by all trans-retinoic acid treatment but this did not occur in the androgen-dependent cell lines expressing low levels of Bcl-2. Changes in localization of Par-4, and an induction in the expression of WT1 protein accompanied the decrease in the Bcl-2 protein and transcript following all trans-retinoic acid treatment, in the androgen-independent prostate cancer cell line. In stable clones expressing ectopic Par-4 we observed decreased Bcl-2 protein and transcript. This was accompanied by an induction in WT1 expression. Finally, we detected Par-4 and WT1 proteins binding to a previously identified WT1 binding site on the bcl-2 promoter both in vitro and in vivo leading to a decrease in transcription from the bcl-2 promoter. We conclude that Par-4 regulates Bcl-2 through a WT1 binding site on the bcl-2 promoter. ^

Community structure and biodiversity in marine benthic communities during experiments, 2011

A mesocosm experiment was conducted to quantify the effects of reduced pH and elevated temperature on an intact marine invertebrate community. Standardised faunal communities, collected from the extreme low intertidal zone using artificial substrate units, were exposed to one of eight nominal treatments (four pH levels: 8.0, 7.7, 7.3 and 6.7, crossed with two temperature levels: 12 and 16°C). After 60 days exposure communities showed significant changes in structure and lower diversity in response to reduced pH. The response to temperature was more complex. At higher pH levels (8.0 and 7.7) elevated temperature treatments contained higher species abundances and diversity than the lower temperature treatments. In contrast, at lower pH levels (7.3 and 6.7), elevated temperature treatments had lower species abundances and diversity than lower temperature treatments. The species losses responsible for these changes in community structure and diversity were not randomly distributed across the different phyla examined. Molluscs showed the greatest reduction in abundance and diversity in response to low pH and elevated temperature, whilst annelid abundance and diversity was mostly unaffected by low pH and was higher at the elevated temperature. The arthropod response was between these two extremes with moderately reduced abundance and diversity at low pH and elevated temperature. Nematode abundance increased in response to low pH and elevated temperature, probably due to the reduction of ecological constraints, such as predation and competition, caused by a decrease in macrofaunal abundance. This community-based mesocosm study supports previous suggestions, based on observations of direct physiological impacts, that ocean acidification induced changes in marine biodiversity will be driven by differential vulnerability within and between different taxonomical groups. This study also illustrates the importance of considering indirect effects that occur within multispecies assemblages when attempting to predict the consequences of ocean acidification and global warming on marine communities.

Seawater carbonate chemistry, nutrients, growth rate and phytoplnkton community response to increasing CO2 concentration during experiments, 2011

This paper reports for the first time upon the effects of increasing CO2 concentrations on a natural phytoplankton assemblage in a tropical estuary (the Godavari River Estuary in India). Two short-term (5-day) bottle experiments were conducted (with and without nutrient addition) during the pre-monsoon season when the partial pressure of CO2 in the surface water is quite low. The results reveal that the concentrations of total chlorophyll, the phytoplankton growth rate, the concentrations of particulate organic matter, the photosynthetic oxygen evolution rates, and the total bacterial count were higher under elevated CO2 treatments, as compared to ambient conditions (control). delta13C of particulate organic matter (POM) varied inversely with respect to CO2, indicating a clear signature of higher CO2 influx under the elevated CO2 levels. Whereas, delta13CPOM in the controls indicated the existence of an active bicarbonate transport system under limited CO2 supply. A considerable change in phytoplankton community structure was noticed, with marker pigment analysis by HPLC revealing that cyanobacteria were dominant over diatoms as CO2 concentrations increased. A mass balance calculation indicated that insufficient nutrients (N, P and Si) might have inhibited diatomgrowth compared to cyanobacteria, regardless of increased CO2 supply. The present study suggests that CO2 concentration and nutrient supply could have significant effects on phytoplankton physiology and community composition for natural phytoplankton communities in this region. However, this work was conducted during a non-discharge period (nutrient-limited conditions) and the responses of phytoplankton to increasing CO2 might not necessarily be the same during other seasons with high physicochemical variability. Further investigation is therefore needed.

Effects of ocean acidification on population dynamics and community structure of crustose coralline algae

Calcification and growth of crustose coralline algae (CCA) are affected by elevated seawater pCO2 and associated changes in carbonate chemistry. However, the effects of ocean acidification (OA) on population and community-level responses of CCA have barely been investigated. We explored changes in community structure and population dynamics (size structure and reproduction) of CCA in response to OA. Recruited from an experimental flow-through system, CCA settled onto the walls of plastic aquaria and developed under exposure to one of three pCO2 treatments (control [present day, 389±6 ppm CO2], medium [753±11 ppm], and high [1267±19 ppm]). Elevated pCO2 reduced total CCA abundance and affected community structure, in particular the density of the dominant species Pneophyllum sp. and Porolithon onkodes. Meanwhile, the relative abundance of P. onkodes declined from 24% under control CO2 to 8.3% in high CO2 (65% change), while the relative abundance of Pneophyllum sp. remained constant. Population size structure of P. onkodes differed significantly across treatments, with fewer larger individuals under high CO2. In contrast, the population size structure and number of reproductive structures (conceptacles) per crust of Pneophyllum sp. was similar across treatments. The difference in the magnitude of the response of species abundance and population size structure between species may have the potential to induce species composition changes in the future. These results demonstrate that the impacts of OA on key coral reef builders go beyond declines in calcification and growth, and suggest important changes to aspects of population dynamics and community ecology.

Sea urchin response to rising pCO2 shows ocean acidification may fundamentally alter the chemistry of marine skeletons

Ocean acidification caused by an increase in pCO2 is expected to drastically affect marine ecosystem composition, yet there is much uncertainty about the mechanisms through which ecosystems may be affected. Here we studied sea urchins that are common and important grazers in the Mediterranean (Paracentrotus lividus and Arbacia lixula). Our study included a natural CO2 seep plus reference sites in the Aegean Sea off Greece. The distribution of A. lixula was unaffected by the low pH environment, whereas densities of P. lividus were much reduced. There was skeletal degradation in both species living in acidified waters compared to reference sites and remarkable increases in skeletal manganese levels (P. lividus had a 541% increase, A. lixula a 243% increase), presumably due to changes in mineral crystalline structure. Levels of strontium and zinc were also altered. It is not yet known whether such dramatic changes in skeletal chemistry will affect coastal systems but our study reveals a mechanism that may alter inter-species interactions.

Skeletal trade-offs in coralline algae in response to ocean acidification

Ocean acidification is changing the marine environment, with potentially serious consequences for many organisms. Much of our understanding of ocean acidification effects comes from laboratory experiments, which demonstrate physiological responses over relatively short timescales. Observational studies and, more recently, experimental studies in natural systems suggest that ocean acidification will alter the structure of seaweed communities. Here, we provide a mechanistic understanding of altered competitive dynamics among a group of seaweeds, the crustose coralline algae (CCA). We compare CCA from historical experiments (1981-1997) with specimens from recent, identical experiments (2012) to describe morphological changes over this time period, which coincides with acidification of seawater in the Northeastern Pacific. Traditionally thick species decreased in thickness by a factor of 2.0-2.3, but did not experience a change in internal skeletal metrics. In contrast, traditionally thin species remained approximately the same thickness but reduced their total carbonate tissue by making thinner inter-filament cell walls. These changes represent alternative mechanisms for the reduction of calcium carbonate production in CCA and suggest energetic trade-offs related to the cost of building and maintaining a calcium carbonate skeleton as pH declines. Our classification of stress response by morphological type may be generalizable to CCA at other sites, as well as to other calcifying organisms with species-specific differences in morphological types.

Response of a natural phytoplankton community from the Qingdao coast (Yellow Sea, China) to variable CO2 levels over a short-term incubation experiment

Since marine phytoplankton play a vital role in stabilizing earth's climate by removing significant amount of atmospheric CO2, their responses to increasing CO2 levels are indeed vital to address. The responses of a natural phytoplankton community from the Qingdao coast (NW Yellow Sea, China) was studied under different CO2 levels in microcosms. HPLC pigment analysis revealed the presence of diatoms as a dominant microalgal group; however, members of chlorophytes, prasinophytes, cryptophytes and cyanophytes were also present. delta 13CPOM values indicated that the phytoplankton community probably utilized bicarbonate ions as dissolved inorganic carbon source through a carbon concentration mechanism (CCM) under low CO2 levels, and diffusive CO2 uptake increased upon the increase of external CO2 levels. Although, considerable increase in phytoplankton biomass was noticed in all CO2 treatments, CO2-induced effects were absent. Higher net nitrogen uptake under low CO2 levels could be related to the synthesis of CCM components. Flow cytometry analysis showed slight reduction in the abundance of Synechococcus and pico-eukaryotes under the high CO2 treatments. Diatoms did not show any negative impact in response to increasing CO2 levels; however, chlorophytes revealed a reverse tend. Heterotrophic bacterial count enhanced with increasing CO2 levels and indicated higher abundance of labile organic carbon. Thus, the present study indicates that any change in dissolved CO2 concentrations in this area may affect phytoplankton physiology and community structure and needs further long-term study.

Governance Structure Choices in Supply Chain Management Evidence from Spanish and Chinese Pork Chain Cases

The author participated in the 6 th EU Framework Project ―Q-pork Chains (FP6-036245-2)‖ from 2007 to 2009. With understanding of work reports from China and other countries, it is found that compared with other countries, China has great problems in pork quality and safety. By comparing the pork chain management between China and Spain, It is found that the difference in governance structure is one of the main differences in pork chain management between Spain and China. In China, spot-market relationship still dominates governance structure of pork chain, especially between the numerous house-hold pig holders and the great number of small slaughters. While in Spain, chain agents commonly apply cooperatives or integrations to cooperate. It also has been proven by recent studies, that in quality management at the chain level that supply chain integration has a direct effect on quality management practices (Han, 2010). Therefore, the author started to investigate the governance structure choices in supply chain management. And it has been set as the first research objective, which is to explain the governance structure choices process and the influencing factors in supply chain management, analyzing the pork chains cases in Spain and in China. During the further investigation, the author noticed the international trade of pork between Spain and China is not smooth since the signature of bi-lateral agreement on pork trade in 2007. Thus, another objective of the research is to find and solve the problems exist in the international pork chain between Spain and China. For the first objective, to explain the governance structure choices in supply chain management, the thesis conducts research in three main sections. 10 First of all, the thesis gives a literature overview in chapter two on Supply Chain Management (SCM), agri-food chain management and pork chain management. It concludes that SCM is a systems approach to view the supply chains as a whole, and to manage the total flow of goods inventory from the supplier to the ultimate customer. It includes the bi-directional flow of products (materials and services) and information, and the associated managerial and operational activities. And it also is a customer focus to create unique and individual source of customer value with an appropriate use of resources, leading to customer satisfaction and building competitive chain advantages. Agri-food chain management and pork chain management are applications of SCM in agri-food sector and pork sector respectively. Then, the research gives a comparative study in chapter three in the pork chain and pork chain management between Spain and China. Many differences are found, while the main difference is governance structure in pork chain management. Furthermore, the author gives an empirical study on governance structure choice in chapter five. It is concluded that governance structure of supply chain consists of a collection of rules/institutions/constraints structuring the transactions between the various stakeholders. Based on the overview on literatures closely related with governance structure, such as transaction cost economics, transaction value analysis and resource-based view theories, seven hypotheses are proposed, which are: Hypothesis 1: Transaction cost has positive relationship with governance structure choice Hypothesis 2: Uncertainty has positive relationship with transaction cost; higher uncertainty exerts high transaction cost Hypothesis 3: The relationship between asset specificity and transaction cost is positive Hypothesis 4: Collaboration advantages and governance structure choice have positive relationship11 Hypothesis 5: Willingness to collaborate has positive relationship with collaboration advantages Hypothesis 6: Capability to collaborate has positive relationship with collaboration advantages Hypothesis 7: Uncertainty has negative effect on collaboration advantages It is noted that as transaction cost value is negative, the transaction cost mentioned in the hypotheses is its absolute value. To test the seven hypotheses, Structural Equation Model (SEM) is applied and data collected from 350 pork slaughtering and processing companies in Jiangsu, Shandong and Henan Provinces in China is used. Based on the empirical SEM model and its results, the seven hypotheses are proved. The author generates several conclusions accordingly. It is found that the governance structure choice of the chain not only depends on transaction cost, it also depends on collaboration advantages. Exchange partners establish more stable and more intense relationship to reduce transaction cost and to maximize collaboration advantages. ―Collaboration advantages‖ in this thesis is defined as the joint value achieved through transaction (mutual activities) of agents in supply chains. This value forms as improvements, mainly in mutual logistics systems, cash response, information exchange, technological improvements and innovative improvements and quality management improvements, etc. Governance structure choice is jointly decided by transaction cost and collaboration advantages. Chain agents take different governance structures to coordinate in order to decrease their transaction cost and to increase their collaboration advantages. In China´s pork chain case, spot market relationship dominates the governance structure among the numerous backyard pig farmer and small family slaughterhouse 12 as they are connected by acquaintance relationship and the transaction cost in turn is low. Their relationship is reliable as they know each other in the neighborhood; as a result, spot market relationship is suitable for their exchange. However, the transaction between large-scale slaughtering and processing industries and small-scale pig producers is becoming difficult. The information hold back behavior and hold-up behavior of small-scale pig producers increase transaction cost between them and large-scale slaughtering and processing industries. Thus, through the more intense and stable relationship between processing industries and pig producers, processing industries reduce the transaction cost and improve the collaboration advantages with their chain partners, in which quality and safety collaboration advantages be increased, meaning that processing industries are able to provide consumers products with better quality and higher safety. It is also drawn that transaction cost is influenced mainly by uncertainty and asset specificity, which is in line with new institutional economics theories developed by Williamson O. E. In China´s pork chain case, behavioral uncertainty is created by the hold-up behaviors of great numbers of small pig producers, while big slaughtering and processing industries having strong asset specificity. On the other hand, ―collaboration advantages‖ is influenced by chain agents´ willingness to collaborate and chain agents´ capabilities to cooperate. With the fast growth of big scale slaughtering and processing industries, they are more willing to know and make effort to cooperate with their chain members, and they are more capable to create joint value together with other chain agents. Therefore, they are now the main chain agents who drive more intense and stable governance structure in China‘s pork chain. For the other objective, to find and solve the problems in the international pork chain between Spain and China, the research gives an analysis in chapter four on the 13 international pork chain. This study gives explanations why the international trade of pork between Spain and China is not sufficient from the chain perspective. It is found that the first obstacle is the high quality and safety requirement set by Chinese government. It makes the Spanish companies difficult to get authorities to export. Other aspects, such as Spanish pork is not competitive in price compared with other countries such as Denmark, United States, Canada, etc., Chinese consumers do not have sufficient information on Spanish pork products, are also important reasons that Spain does not export great quantity of pork products to China. It is concluded that China´s government has too much concern on the quality and safety requirements to Spanish pork products, which makes trade difficult to complete. The two countries need to establish a more stable and intense trade relationship. They also should make the information exchange sufficient and efficient and try to break trade barriers. Spanish companies should consider proper price strategies to win the Chinese pork market

Dynamic Response of Wind Turbines to Theoretical 3D Seismic Motions Taking into Account the Rotational Component

We study the dynamic response of a wind turbine structure subjected to theoretical seismic motions, taking into account the rotational component of ground shaking. Models are generated for a shallow moderate crustal earthquake in the Madrid Region (Spain). Synthetic translational and rotational time histories are computed using the Discrete Wavenumber Method, assuming a point source and a horizontal layered earth structure. These are used to analyze the dynamic response of a wind turbine, represented by a simple finite element model. Von Mises stress values at different heights of the tower are used to study the dynamical structural response to a set of synthetic ground motion time histories

Non-linear gain - look-up table based approach for modeling a family of DC to DC converters based on transient response analysis

The purpose of this work is to propose a structure for simulating power systems using behavioral models of nonlinear DC to DC converters implemented through a look-up table of gains. This structure is specially designed for converters whose output impedance depends on the load current level, e.g. quasi-resonant converters. The proposed model is a generic one whose parameters can be obtained by direct measuring the transient response at different operating points. It also includes optional functionalities for modeling converters with current limitation and current sharing in paralleling characteristics. The pusposed structured also allows including aditional characteristics of the DC to DC converter as the efficency as a function of the input voltage and the output current or overvoltage and undervoltage protections. In addition, this proposed model is valid for overdamped and underdamped situations.

Dynamic response of underpasses for high-speed train lines

Underpasses are common in modern railway lines. Wildlife corridors and drainage conduits often fall into this category of partially buried structures. Their dynamic behavior has received far less attention than that of other structures such as bridges, but their large number makes their study an interesting challenge from the viewpoint of safety and cost savings. Here, we present a complete study of a culvert, including on-site measurements and numerical modeling. The studied structure belongs to the high-speed railway line linking Segovia and Valladolid in Spain. The line was opened to traffic in 2004. On-site measurements were performed for the structure by recording the dynamic response at selected points of the structure during the passage of high-speed trains at speeds ranging between 200 and 300 km/h. The measurements provide not only reference values suitable for model fitting, but also a good insight into the main features of the dynamic behavior of this structure. Finite element techniques were used to model the dynamic behavior of the structure and its key features. Special attention is paid to vertical accelerations, the values of which should be limited to avoid track instability according to Eurocode. This study furthers our understanding of the dynamic response of railway underpasses to train loads.

Abutments influence in the dynamic response of bridges

A simplified analytical model of a short span bridge is proposed. The inertial interaction effects of pier foundations and abutments has been included in order to evaluate the response sensitivities to different soil-structure interaction variables. The modification of natural frequency and damping properties is shown for typical short span bridges of the integral deck-abutment type for longitudinal vibrations or general bridges for the transverse ones.

Physical and mathematical modeling of wave propagation in the Ariane 5 VEB structure

The separation of the lower stage of the ARIANE 5 Vehicle Equipment Bay (VEB) Structure is to be done using a pyrotechnic device. The wave propagation effects produced by the explosion can affect the electronic equipment, so it was decided to analyze, using both physical and numerical modeling, a small piece of the structure to determine the distribution of the accelerations and the relative importance of damping, stiffness, connections, etc. on the response of the equipment.