Increased TG2 expression can result in induction of transforming growth factor β1, causing increased synthesis and deposition of matrix proteins, which can be regulated by nitric oxide

In fibrotic conditions increases in TG2 activity has been linked to an increase in the deposition of extracellular matrix proteins. Using TG2 transfected Swiss 3T3 fibroblasts expressing TG2 under the control of the tetracycline-regulated inducible promoter, we demonstrate that induction of TG2 not only stimulates an increase in collagen and fibronectin deposition but also an increase in the expression of these proteins. Increased TG2 expression in these fibroblasts led to NF-kappaB activation, resulting in the increased expression of transforming growth factor (TGF) beta(1). In addition, cells overexpressing TG2 demonstrated an increase in biologically active TGFbeta(1) in the extracellular environment. A specific site-directed inhibitor of TG abolished the NF-kappaB and TGFbeta1 activation and the subsequent elevation in the synthesis and deposition of extracellular matrix proteins, confirming that this process depends on the induction of transglutaminase activity. Treatment of TG2-induced fibroblasts with nontoxic doses of nitric oxide donor S-nitroso-N-acetylpenicillamine resulted in decreased TG2 activity and apprehension of the inactive enzyme on the cell surface. This was paralleled by a reduction in activation of NF-kappaB and TGFbeta(1) production with a subsequent decrease in collagen expression and deposition. These findings support a role for NO in the regulation of TG2 function in the extracellular environment.

Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy?

Background. Diabetic nephropathy is the leading cause of end-stage kidney failure worldwide. It is characterized by excessive extracellular matrix accumulation. Transforming growth factor beta 1 (TGF-ß1) is a fibrogenic cytokine playing a major role in the healing process and scarring by regulating extracellular matrix turnover, cell proliferation and epithelial mesanchymal transdifferentiation. Newly synthesized TGF-ß is released as a latent, biologically inactive complex. The cross-linking of the large latent TGF-ß to the extracellular matrix by transglutaminase 2 (TG2) is one of the key mechanisms of recruitment and activation of this cytokine. TG2 is an enzyme catalyzing an acyl transfer reaction leading to the formation of a stable e(?-glutamyl)-lysine cross-link between peptides.Methods. To investigate if changes in TG activity can modulate TGF-ß1 activation, we used the mink lung cell bioassay to assess TGF-ß activity in the streptozotocin model of diabetic nephropathy treated with TG inhibitor NTU281 and in TG2 overexpressing opossum kidney (OK) proximal tubular epithelial cells.Results. Application of the site-directed TG inhibitor NTU281 caused a 25% reduction in kidney levels of active TGF-ß1. Specific upregulation of TG2 in OK proximal tubular epithelial cells increased latent TGF-ß recruitment and activation by 20.7% and 19.7%, respectively, in co-cultures with latent TGF-ß binding protein producing fibroblasts.Conclusions. Regulation of TG2 directly influences the level of active TGF-ß1, and thus, TG inhibition may exert a renoprotective effect by targeting not only a direct extracellular matrix deposition but also TGF-ß1 activation and recruitment.

Applications of Reissner's principle to structural dynamics

The analysis and prediction of the dynamic behaviour of s7ructural components plays an important role in modern engineering design. :n this work, the so-called "mixed" finite element models based on Reissnen's variational principle are applied to the solution of free and forced vibration problems, for beam and :late structures. The mixed beam models are obtained by using elements of various shape functions ranging from simple linear to complex cubic and quadratic functions. The elements were in general capable of predicting the natural frequencies and dynamic responses with good accuracy. An isoparametric quadrilateral element with 8-nodes was developed for application to thin plate problems. The element has 32 degrees of freedom (one deflection, two bending and one twisting moment per node) which is suitable for discretization of plates with arbitrary geometry. A linear isoparametric element and two non-conforming displacement elements (4-node and 8-node quadrilateral) were extended to the solution of dynamic problems. An auto-mesh generation program was used to facilitate the preparation of input data required by the 8-node quadrilateral elements of mixed and displacement type. Numerical examples were solved using both the mixed beam and plate elements for predicting a structure's natural frequencies and dynamic response to a variety of forcing functions. The solutions were compared with the available analytical and displacement model solutions. The mixed elements developed have been found to have significant advantages over the conventional displacement elements in the solution of plate type problems. A dramatic saving in computational time is possible without any loss in solution accuracy. With beam type problems, there appears to be no significant advantages in using mixed models.

Computer integrated manufacturing (CIM) and the principle of business control

In response to the increasing international competitiveness, many manufacturing businesses are rethinking their management strategies and philosophies towards achieving a computer integrated environment. The explosive growth in Advanced Manufacturing Technology (AMI) has resulted in the formation of functional "Islands of Automation" such as Computer Aided Design (CAD), Computer Aided Manufacturing (CAM), Computer Aided Process Planning (CAPP) and Manufacturing Resources Planning (MRPII). This has resulted in an environment which has focussed areas of excellence and poor overall efficiency, co-ordination and control. The main role of Computer Integrated Manufacturing (CIM) is to integrate these islands of automation and develop a totally integrated and controlled environment. However, the various perceptions of CIM, although developing, remain focussed on a very narrow integration scope and have consequently resulted in mere linked islands of automation with little improvement in overall co-ordination and control. This thesis, that is the research described within, develops and examines a more holistic view of CIM, which is based on the integration of various business elements. One particular business element, namely control, has been shown to have a multi-facetted and underpinning relationship with the CIM philosophy. This relationship impacts various CIM system design aspects including the CIM business analysis and modelling technique, the specification of systems integration requirements, the CIM system architectural form and the degree of business redesign. The research findings show that fundamental changes to CIM system design are required; these are incorporated in a generic CIM design methodology. The affect and influence of this holistic view of CIM on a manufacturing business has been evaluated through various industrial case study applications. Based on the evidence obtained, it has been concluded that this holistic, control based approach to CIM can provide a greatly improved means of achieving a totally integrated and controlled business environment. This generic CIM methodology will therefore make a significant contribution to the planning, modelling, design and development of future CIM systems.

Strategic HRM:transforming its responsibilities toward ecological sustainability - the greatest global challenge facing organizations

If we are to move to a more sustainable world, all actorsÑincluding governments, organizations, communities, and individualsÑneed to play their part in committing to a shift in the way we live our lives. This conceptual article explores the challenges that face the human resource management (HRM) profession in moving to a strategic position that supports the requirements of the biophysical environment. We argue that this is becoming an imperative for the future survival and success of organizations large and small, and thus is likely to be a key "modus operandi" for HRM professionals in the future who are looking to embed ecological sustainability into their organizations. This article offers new insights into developing business strategies for ecological sustainability, highlighting the implications for strategic HRM activity through organizational effectiveness, leadership, values, and, ultimately, HRM processes and systems.

Applications of the Sufficiency Principle in Acceleration of Neural Networks Trainig

One of the problems in AI tasks solving by neurocomputing methods is a considerable training time. This problem especially appears when it is needed to reach high quality in forecast reliability or pattern recognition. Some formalised ways for increasing of networks’ training speed without loosing of precision are proposed here. The offered approaches are based on the Sufficiency Principle, which is formal representation of the aim of a concrete task and conditions (limitations) of their solving [1]. This is development of the concept that includes the formal aims’ description to the context of such AI tasks as classification, pattern recognition, estimation etc.

A Fractional Analog of the Duhamel Principle

Mathematics Subject Classification: 35CXX, 26A33, 35S10

Application of Subordination Principle to Log-Harmonic alpha-spirallike Mappings

MSC 2010: 30C45, 30C55

Applications of Subordination Principle to Log-Harmonic Mappings

MSC 2010: 30C45, 30C55

Hamilton’s Principle with Variable Order Fractional Derivatives

MSC 2010: 26A33, 70H25, 46F12, 34K37 Dedicated to 80-th birthday of Prof. Rudolf Gorenflo

Maximum Principle and Its Application for the Time-Fractional Diffusion Equations

MSC 2010: 26A33, 33E12, 35B45, 35B50, 35K99, 45K05 Dedicated to Professor Rudolf Gorenflo on the occasion of his 80th anniversary

Transforming Mathematics Learning for Students and Teachers with Digital Technologies

Силия Хойлс, Ричардс Нос - Това представяне е вдъхновено от делото на Сиймър Пепърт и много други от целия свят (включително Джим Капут и наши колеги от България), които са работили и работят в духа на конструкционизма и с които сме имали щастието да си сътрудничим в областта на математическото образование и дигиталните технологии в течение на десетилетия.

On Principle Eigenvalue for Linear Second Order Elliptic Equations in Divergence Form

2002 Mathematics Subject Classification: 35J15, 35J25, 35B05, 35B50

Minimum Description Length Principle in Discriminating Marginal Distributions

2010 Mathematics Subject Classification: 94A17, 62B10, 62F03.