7 resultados para Tökes, László: Toivoa emme menettäneet

em Aston University Research Archive


Relevância:

10.00% 10.00%

Publicador:

Resumo:

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin ß(3) coreceptor in the engulfment process, while altered proinflammatory cytokine production is related to the lack of latent TGFß activation by TG2 null macrophages. Here we report that TG2 null macrophages respond to lipopolysaccharide treatment by elevated IL-6 and TNFa production. Though TGFß has been proposed to act as a feed back regulator of proinflammatory cytokine production in LPS-stimulated macrophages, this phenomenon is not related to the lack of active TGFß production. Instead, in the absence of TG2 integrin ß(3) maintains an elevated basal Src family kinase activity in macrophages, which leads to enhanced phosphorylation and degradation of the I?Ba. Low basal levels of I?Ba explain the enhanced sensitivity of TG2 null macrophages to signals that regulate NF-?B. Our data suggest that TG2 null macrophages bear a proinflammatory phenotype, which might contribute to the enhanced susceptibility of these mice to develop autoimmunity and atherosclerosis.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

In this research summary, we provide a novel look into the entrepreneurial profile of the UK in an international context. We use a new method – the Global Entrepreneurship and Development Index GEDI – to identify the entrepreneurial strengths and weaknesses of the UK economy, as well as to identify potential bottlenecks that hold back the performance of the UK relative to other advanced economies. We perform a Penalty for Bottleneck analysis to identify the bottlenecks in the UK's entrepreneurial profile. We also explore optimal resource allocation for UK's policy for National Systems of Entrepreneurship.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The combination of dwindling oil reserves and growing concerns over carbon dioxide emissions and associated climate change is driving the urgent development of routes to utilise renewable feedstocks as sustainable sources of fuel and chemicals. Catalysis has a rich history of facilitating energy-efficient selective molecular transformations and contributes to 90% of chemical manufacturing processes and to more than 20% of all industrial products. In a post-petroleum era, catalysis will be central to overcoming the engineering and scientific barriers to economically feasible routes to biofuels and chemicals. This chapter will highlight some of the recent developments in heterogeneous catalytic technology for the synthesis of fuels and chemicals from renewable resources, derived from plant and aquatic oil sources as well as lignocellulosic feedstocks. Particular attention will be paid to the challenges faced when developing new catalysts and importance of considering the design of pore architectures and effect of tuning surface polarity to improve catalyst compatibility with highly polar bio-based substrates.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

One dominant feature of the modern manufacturing chains is the movement of goods. Manufacturing companies would remain an unprofitable investment if the supplies/logistics of raw materials, semi-finished products or final goods are not handled in an effective way. Both levels of a modern manufacturing chain-actual production and logistics-are characterized by continuous data creation at a much faster rate than they can be meaningfully analyzed and acted upon manually. Often, instant and reliable decisions need to be taken based on huge, previously inconceivable amounts of heterogeneous, contradictory or incomplete data. The paper will highlight aspects of information flows related to business process data visibility and observability in modern manufacturing networks. An information management platform developed in the framework of the EU FP7 project ADVANCE will be presented.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Transglutaminase 2 (TG2) is a multifunctional protein with diverse catalytic activities and biological roles. Its best studied function is the Ca2+-dependent transamidase activity leading to formation of γ-glutamyl-ε-lysine isopeptide crosslinks between proteins or γ-glutamyl-amine derivatives. TG2 has a poorly studied isopeptidase activity cleaving these bonds. We have developed and characterised TG2 mutants which are significantly deficient in transamidase activity while have normal or increased isopeptidase activity (W332F) and vice versa (W278F). The W332F mutation led to significant changes of both the Km and the Vmax kinetic parameters of the isopeptidase reaction of TG2 while its calcium and GTP sensitivity was similar to the wild type enzyme. The W278F mutation resulted in six times elevated amine incorporating transamidase activity demonstrating the regulatory significance of W278 and W332 in TG2 and that mutations can change opposed activities located at the same active site. The further application of our results in cellular systems may help to understand TG2 -driven physiological and pathological processes better and lead to novel therapeutic approaches where an increased amount of cross-linked proteins correlates with the manifestation of degenerative disorders.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Purpose – The purpose of this paper is to examine challenges and potential of big data in heterogeneous business networks and relate these to an implemented logistics solution. Design/methodology/approach – The paper establishes an overview of challenges and opportunities of current significance in the area of big data, specifically in the context of transparency and processes in heterogeneous enterprise networks. Within this context, the paper presents how existing components and purpose-driven research were combined for a solution implemented in a nationwide network for less-than-truckload consignments. Findings – Aside from providing an extended overview of today’s big data situation, the findings have shown that technical means and methods available today can comprise a feasible process transparency solution in a large heterogeneous network where legacy practices, reporting lags and incomplete data exist, yet processes are sensitive to inadequate policy changes. Practical implications – The means introduced in the paper were found to be of utility value in improving process efficiency, transparency and planning in logistics networks. The particular system design choices in the presented solution allow an incremental introduction or evolution of resource handling practices, incorporating existing fragmentary, unstructured or tacit knowledge of experienced personnel into the theoretically founded overall concept. Originality/value – The paper extends previous high-level view on the potential of big data, and presents new applied research and development results in a logistics application.