FUNCTIONAL CHARACTERIZATION OF THE LINK BETWEEN CARBOHYDRATE METABOLISM AND THE PATHOGENESIS OF THE INVASIVE M1T1 GROUP A STREPTOCOCCUS

The Group A Streptococcus (GAS), or Streptococcus pyogenes, is a strict human pathogen that colonizes a variety of sites within the host. Infections can vary from minor and easily treatable, to life-threatening, invasive forms of disease. In order to adapt to niches, GAS utilizes environmental cues, such as carbohydrates, to coordinate the expression of virulence factors. Research efforts to date have focused on identifying how either components of the phosphoenolpyruvate-phosphotransferase system (PTS) or global transcriptional networks affect the regulation of virulence factors, but not the synergistic relationship between the two. The present study investigates the role of a putative PTS-fructose operon encoded by fruRBA and its role in virulence in the M1T1 strain 5448. Growth in fructose resulted in induction of fruRBA. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose. Growth and carbon utilization profiles revealed that although the entire fruRBA operon was required for growth in fructose, FruA was the main fructose transporter. The ability of both ΔfruR and ΔfruB mutants to survive in whole human blood or neutrophils was impaired. However, the phenotypes were not reproduced in murine whole blood or in a mouse intraperitoneal infection, indicating a human-specific mechanism. While it is known that the PTS can affect activity of the Mga virulence regulator, further characterization of the mechanism by which sugars and its protein domains affect activity have not been studied. Transcriptional studies revealed that the core Mga regulon is activated more in a glucose-rich than a glucose-poor environment. This activation correlates with the differential phosphorylation of Mga at its PTS regulatory domains (PRDs). Using a 5448 mga mutant, transcriptome studies in THY or C media established that the Mga regulon reflects the media used. Interestingly, Mga regulates phage-encoded DNases in a low glucose environment. We also show that Mga activity is dependent on C-terminal amino acid interactions that aid in the formation of homodimers. Overall, the studies presented sought to define how external environmental cues, specifically carbohydrates, control complex regulatory networks used by GAS, contribute to pathogenesis, and aid in adaptation to various nutrient conditions encountered.

An intimate link between antimicrobial peptide sequence diversity and binding to essential components of bacterial membranes

Antimicrobial peptides and proteins (AMPs) are widespread in the living kingdom. They are key effectors of defense reactions and mediators of competitions between organisms. They are often cationic and amphiphilic, which favors their interactions with the anionic membranes of microorganisms. Several AMP families do not directly alter membrane integrity but rather target conserved components of the bacterial membranes in a process that provides them with potent and specific antimicrobial activities. Thus, lipopolysaccharides (LPS), lipoteichoic acids (LTA) or the peptidoglycan precursor Lipid II are targeted by a broad series of AMPs. Studying the functional diversity of immune effectors tells us about the essential residues involved in AMP mechanism of action. Marine invertebrates have been found to produce a remarkable diversity of AMPs. Molluscan defensins and crustacean anti-LPS factors (ALF) are diverse in terms of amino acid sequence and show contrasted phenotypes in terms of antimicrobial activity. Their activity is directed essentially against Gram-positive or Gram-negative bacteria due their specific interactions with Lipid II or Lipid A, respectively. Through those interesting examples, we discuss here how sequence diversity generated throughout evolution informs us on residues required for essential molecular interaction at the bacterial membranes and subsequent antibacterial activity. Through the analysis of molecular variants having lost antibacterial activity or shaped novel functions, we also discuss the molecular bases of functional divergence in AMPs.

The fluorescence detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions. (C) 2010 Elsevier B.V All rights reserved.

Is the supply of long-term debt independent of the term premia? Evidence from Portugal

An important assumption in the statistical analysis of the financial market effects of the central bank’s large scale asset purchase program is that the "long-term debt stock variables were exogenous to term premia". We test this assumption for a small open economy in a currency union over the period 2000M3 to 2015M10, via the determinants of short- term financing relative to long-term financing. Empirical estimations indicate that the maturity composition of debt does not respond to the level of interest rate or to the term structure. These findings suggest a lower adherence to the cost minimization mandate of debt management. However, we find that volatility and relative market size respectively decrease and increase short-term financing relative to long-term financing, while it decreases with an increase in government indebtedness.

Development of a 1-D Catalyzed Diesel Particulate Filter Model for Simulation of the Performance and the Oxidation of Particulate Matter and Nitrogen Oxides Using Passive Oxidation and Active Regeneration Engine Experimental Data

Back-pressure on a diesel engine equipped with an aftertreatment system is a function of the pressure drop across the individual components of the aftertreatment system, typically, a diesel oxidation catalyst (DOC), catalyzed particulate filter (CPF) and selective catalytic reduction (SCR) catalyst. Pressure drop across the CPF is a function of the mass flow rate and the temperature of the exhaust flowing through it as well as the mass of particulate matter (PM) retained in the substrate wall and the cake layer that forms on the substrate wall. Therefore, in order to control the back-pressure on the engine at low levels and to minimize the fuel consumption, it is important to control the PM mass retained in the CPF. Chemical reactions involving the oxidation of PM under passive oxidation and active regeneration conditions can be utilized with computer numerical models in the engine control unit (ECU) to control the pressure drop across the CPF. Hence, understanding and predicting the filtration and oxidation of PM in the CPF and the effect of these processes on the pressure drop across the CPF are necessary for developing control strategies for the aftertreatment system to reduce back-pressure on the engine and in turn fuel consumption particularly from active regeneration. Numerical modeling of CPF's has been proven to reduce development time and the cost of aftertreatment systems used in production as well as to facilitate understanding of the internal processes occurring during different operating conditions that the particulate filter is subjected to. A numerical model of the CPF was developed in this research work which was calibrated to data from passive oxidation and active regeneration experiments in order to determine the kinetic parameters for oxidation of PM and nitrogen oxides along with the model filtration parameters. The research results include the comparison between the model and the experimental data for pressure drop, PM mass retained, filtration efficiencies, CPF outlet gas temperatures and species (NO2) concentrations out of the CPF. Comparisons of PM oxidation reaction rates obtained from the model calibration to the data from the experiments for ULSD, 10 and 20% biodiesel-blended fuels are presented.

Waterpower : a geophysical and archaeological investigation of the waterpower system at the West Point Foundry, Cold Spring, New York

Waterpower: A Geophysical and Archaeological Investigation of the Waterpower System at the West Point Foundry, Cold Spring, New York, describes the results of ground penetrating radar surveys and archaeological excavation undertaken by Michigan Technological University (MTU) archaeologists during the summer of 2003 at the West Point Foundry, Cold Spring, New York. 2003 constituted MTU's second field season at the foundry. Fieldwork concentrated on the foundry's waterpower system, an intricate network of surface and subsurface drains, races, flumes, waterwheels, turbines, dams, and ponds that powered operations and regulated water flow throughout the site. Archaeologists utilized non-destructive geophysical technology, which expedited survey, facilitated placement of excavation units, and provided a model for future archaeogeophysical research at industrial sites. Features discovered during excavation provided valuable information pertaining to the waterpower system's construction and its functions. Data from ground penetrating radar surveys, archaeological excavation, historical photographs, documents, and maps permitted the development of a provisional chronology of the development of various components of the West Point Foundry's waterpower system. Information gathered during this project serves as an aid in sit interpretation and rehabilitation.

Stepwise evolution of the centriole-assembly pathway

The centriole and basal body (CBB) structure nucleates cilia and flagella, and is an essential component of the centrosome, underlying eukaryotic microtubule-based motility, cell division and polarity. In recent years, components of the CBB-assembly machinery have been identified, but little is known about their regulation and evolution. Given the diversity of cellular contexts encountered in eukaryotes, but the remarkable conservation of CBB morphology, we asked whether general mechanistic principles could explain CBB assembly. We analysed the distribution of each component of the human CBB-assembly machinery across eukaryotes as a strategy to generate testable hypotheses. We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs. Unexpectedly, other players (SAK/PLK4, SPD2/CEP192 and CP110) emerged in a taxon-specific manner. We report that gene duplication plays an important role in the evolution of CBB components and show that, in the case of BLD10/CEP135, this is a source of tissue specificity in CBB and flagella biogenesis. Moreover, we observe extreme protein divergence amongst CBB components and show experimentally that there is loss of cross-species complementation among SAK/PLK4 family members, suggesting species-specific adaptations in CBB assembly. We propose that the UNIMOD theory explains the conservation of CBB architecture and that taxon- and tissue-specific molecular innovations, gained through emergence, duplication and divergence, play important roles in coordinating CBB biogenesis and function in different cellular contexts.

State of the art of industrial wood protection in Portugal

This work intended to give a perspective of industrial wood protection in Portugal. A survey was made of the companies treating wood mainly for use classes 3 and 4 such as autoclave treatments with biocides and wood modification procedures. Currently there are 23 companies with 33 production plants with an autoclave installed for wood preservation by impregnation. There are also two companies producing modified wood by thermal treatment. Most of the plants are located in the central and northern regions of Portugal. The leading preservation chemicals used in Portugal are Tanalith E and Celcure brands. The main wood species used in all companies is Pinus pinaster from local producers. The products commercialized by the treating companies are diverse: pre-fabricated houses, garden furniture and playgrounds, decks, poles, stakes, and sawn wood. Modified wood producers sell mostly decks and cladding. Considerable changes are expected in the next few years due to the requirements of European Directives and the typical constraints of the Portuguese market.

Unmasking of the trigemino-accessory reflex in accessory facial anastomosis

To evaluate the possible blink reflex responses in facial muscles reinnervated by the accessory nerve. Method: Eleven patients with a complete facial palsy were submitted to a surgical repair by an accessory facial nerve anastomosis (AFA). In this pathological group, blink reflex was studied by means of percutaneous electrical stimulation of the supraorbital nerve and recording from the orbicularis oculi muscle. A control group comprised seven normal people and seven patients with a complete Bell's facial palsy; in this group, responses on the sternocleidomastoideus (SCM) muscles were studied after supraorbital nerve stimulation. Results: All the patients with AFA showed a consistent degree of facial reinnervation. Ten out of the 11 patients with AFA showed reflex responses; in six, responses were configured by a double component pattern, resembling the R1 and R2 components of the blink reflex; three patients had an R1-like response and one patient showed a unique R2 component. Mean values of latencies were 15.2 (SD 4.6) ms for the R1 and 85.3 (SD 9.6) ms for the R2. In the control group, eight out of 14 people had evidence of reflex responses in the SCM muscles; these were almost exclusively configured by a bilateral late component (mean latency 63.5 (SD 15.9) ms) and only one of the subjects showed an early response at 11 ms. Conclusion: The trigemino-accessory reflex response in the pathological group was more complex and of a significantly higher incidence than in the control group. These differences could be tentatively explained by a mechanism of synaptic plasticity induced by the impairment of the efferent portion of the reflex. This could unmask the central linking between the trigeminal and the accessory limbs of the reflex. The findings described could be a demonstration of neurobionomic function in the repairing process of the nervous system.

Information and communication technology for E-regions

Information and communication technologies (ICTs) are essential components of the knowledge economy, and have an immense complementary role in innovation, education, knowledge creation, and relations with government, civil society, and business within city regions. The ability to create, distribute, and exploit knowledge has become a major source of competitive advantage, wealth creation, and improvements in the new regional policies. Growing impact of ICTs on the economy and society, rapid application of recent scientific advances in new products and processes, shifting to more knowledge-intensive industry and services, and rising skill requirements have become crucial concepts for urban and regional competitiveness. Therefore, harnessing ICTs for knowledge-based urban development (KBUD) has a significant impact on urban and regional growth (Yigitcanlar, 2005). In this sense, e-region is a novel concept utilizing ICTs for regional development. Since the Helsinki European Council announced Turkey as a candidate for European Union (EU) membership in 1999, the candidacy has accelerated the speed of regional policy enhancements and adoption of the European regional policy standards. These enhancements and adoption include the generation of a new regional spatial division, NUTS-II statistical regions; a new legislation on the establishment of regional development agencies (RDAs); and new orientations in the field of high education, science, and technology within the framework of the EU’s Lisbon Strategy and the Bologna Process. The European standards posed an ambitious new agenda in the development and application of contemporary regional policy in Turkey (Bilen, 2005). In this sense, novel regional policies in Turkey necessarily endeavor to include information society objectives through efficient use of new technologies such as ICTs. Such a development seeks to be based on tangible assets of the region (Friedmann, 2006) as well as the best practices deriving from grounding initiatives on urban and local levels. These assets provide the foundation of an e-region that harnesses regional development in an information society context. With successful implementations, the Marmara region’s local governments in Turkey are setting the benchmark for the country in the implementation of spatial information systems and e-governance, and moving toward an e-region. Therefore, this article aims to shed light on organizational and regional realities of recent practices of ICT applications and their supply instruments based on evidence from selected local government organizations in the Marmara region. This article also exemplifies challenges and opportunities of the region in moving toward an e-region and provides a concise review of different ICT applications and strategies in a broader urban and regional context. The article is organized in three parts. The following section scrutinizes the e-region framework and the role of ICTs in regional development. Then, Marmara’s opportunities and challenges in moving toward an e-region are discussed in the context of ICT applications and their supply instruments based on public-sector projects, policies, and initiatives. Subsequently, the last section discusses conclusions and prospective research.

Why new business development projects fail : coping with the differences of technological versus market knowledge

Managing through projects has become important for generating new knowledge to cope with technological and market discontinuities. This paper examines how the fit between the creation of technological and market knowledge and important project management characteristics, i.e. project autonomy and completion criteria, influences the success of new business development (NBD) projects. In-depth longitudinal case research on NBD projects commercialised from 1993 to 2003 in the consumer electronics industry highlights that project management characteristics focusing only on the creation of technological knowledge contributed to the failure of those NBD projects that required new market knowledge as well. The findings indicate that senior management support and engaging in an alliance with partners possessing complementary market knowledge can offset this misalignment of the organisation of NBD projects.

The role of the internet on international market growth of Australian firms : an exploratory study

The Internet has been shown to positively influence the internationalisation activities of firms through enhanced information, knowledge and network development. Although there has been evidence of a positive impact of the Internet on internationalisation process components, it is vague as to whether the Internet has an impact on firm international market growth. This paper examines the role of the Internet in the outward internationalisation of a cross-national sample of 224 firms from Australia. The results show evidence that a there is a link between Internet usage, Internet intensity and the international market growth of the firm. The findings indicate that firms are using Internet technologies beyond simple e-mail and websites in their international marketing. For example, Internet directories and Internet market spaces are assisting international market expansion of the firm. Firms are integrating the Internet into international marketing processes such as advertising, marketing, market research and international market management as well as in data transference between company and supplier and company and customer. Further, there is evidence in this study of the statistical relationships between the use of website, e-mail and online sales with the international market growth of the firm.

The emergence of knowledge exchange:an agent-based model of a software market

We investigate knowledge exchange among commercial organizations, the rationale behind it, and its effects on the market. Knowledge exchange is known to be beneficial for industry, but in order to explain it, authors have used high-level concepts like network effects, reputation, and trust. We attempt to formalize a plausible and elegant explanation of how and why companies adopt information exchange and why it benefits the market as a whole when this happens. This explanation is based on a multiagent model that simulates a market of software providers. Even though the model does not include any high-level concepts, information exchange naturally emerges during simulations as a successful profitable behavior. The conclusions reached by this agent-based analysis are twofold: 1) a straightforward set of assumptions is enough to give rise to exchange in a software market, and 2) knowledge exchange is shown to increase the efficiency of the market.