Control of proliferation in the rat thymus

Quiescent rat thymocytes were stimulated to divide by a variety of agents. One such mitogen was the neurotransmitter acetylcholine which exhibited a biphasic action. Interaction with low affinity nicotinic receptors was linked with an obligatory requirement for magnesium ions whereas combination with high affinity muscarinic receptors induced mitosis only if calcium ions were present in the medium. Binding of acetylcholine to its muscarinic receptor enhanced calcium influx and increased intracellular calcium levels causing calmodulin activation, a necessary prelude to DNA synthesis and mitosis. Nicotinic receptor activation may be associated with a magnesium influx and stimulation of cells in a calmodulin-independent fashion. Parathyroid hormone and its analogues exhibited only a monophasic mitogenic action. This response was linked to calcium influx, a rise in cytosolic calcium and calmodulin activation. Parathyroid hormone did not stimulate adenylate cyclase in thymocytes and decreased cellular cyclic AMP concentrations. Picomolar amounts of interleukin-2 (IL-2) also stimulated division in thymocytes derived from 3-month old rats by binding to high affinity receptors. The response in thymocytes from newborn and foetal animals was greater reflecting the larger proportion of cells bearing receptors at this age. The mitogenic effect of IL-2 was abolished by a monoclonal antibody directed against the IL-2 receptor. Injections of IL-2 itself or the administration of IL-2 secreting activated syngeneic spleen cells also stimulated proliferation of both thymus and bone marrow cells in vivo. Likewise immunisation with pertussis toxin, which enhances endogenous IL2 production, also increased mitosis in these tissues. Calcium influx, increased cytosolic Ca2+ levels and calmodulin activation are associated features of the mitogenic action of IL-2. Interleukin-1 was also found to be mitogenic in thymic lymphocyte cultures. The responses to this mitogen and to parathyroid hormone and acetylcholine were not inhibited by the anti-IL2 receptor antibody suggesting that the thymic lymphocyte bears discrete receptors for these agents. Subtle interactions of hormones, neurotransmitters and interleukins may thus contribute to the turnover and control of lymphoid cells in the thymus and perhaps bone-marrow.

The dynamics and control of a remotely piloted plan-symmetric helicopter

Prior to the development of a production standard control system for ML Aviation's plan-symmetric remotely piloted helicopter system, SPRITE, optimum solutions to technical requirements had yet to be found for some aspects of the work. This thesis describes an industrial project where solutions to real problems have been provided within strict timescale constraints. Use has been made of published material wherever appropriate, new solutions have been contributed where none existed previously. A lack of clearly defined user requirements from potential Remotely Piloted Air Vehicle (RPAV) system users is identified, A simulation package is defined to enable the RPAV designer to progress with air vehicle and control system design, development and evaluation studies and to assist the user to investigate his applications. The theoretical basis of this simulation package is developed including Co-axial Contra-rotating Twin Rotor (CCTR), six degrees of freedom motion, fuselage aerodynamics and sensor and control system models. A compatible system of equations is derived for modelling a miniature plan-symmetric helicopter. Rigorous searches revealed a lack of CCTR models, based on closed form expressions to obviate integration along the rotor blade, for stabilisation and navigation studies through simulation. An economic CCTR simulation model is developed and validated by comparison with published work and practical tests. Confusion in published work between attitude and Euler angles is clarified. The implementation of package is discussed. dynamic adjustment of assessment. the theory into a high integrity software Use is made of a novel technique basing the integration time step size on error Simulation output for control system stability verification, cross coupling of motion between control channels and air vehicle response to demands and horizontal wind gusts studies are presented. Contra-Rotating Twin Rotor Flight Control System Remotely Piloted Plan-Symmetric Helicopter Simulation Six Degrees of Freedom Motion ( i i)

The control of technological change in the motor industry:a case study

This thesis is based upon a case study of the introduction of automated production technologies at the Longbridge plant of British Leyland in the period 1978 to 1980.The investment in automation was part of an overall programme of modernization to manufacture the new 'Mini Metro' model. In the first Section of the thesis, the different theoretical perspectives on technological change are discussed. Particular emphasis is placed upon the social role of management as the primary controllers of technological change. Their actions are seen to be oriented towards the overall strategy of the firm, integrating the firm's competitive strategy with production methods and techniques.This analysis is grounded in an examination of British Leyland's strategies during the 1970s.. The greater part of the thesis deals with the efforts made by management to secure their strategic objectives in the process of technological change against the conflicting claims of their work-force. Examination of these efforts is linked to the development of industrial relations conflict at Longbridge and in British Leyland as a whole.Emphasis is placed upon the struggle between management in pursuit of their version of efficiency and the trade unions in defence of job controls and demarcations. The thesis concludes that the process of technological change in the motor industry is controlled by social forces,with the introduction of new technologies being closely intertwined with management!s political relations with the trade unions.

GPCR production in a novel yeast strain that makes cholesterol-like sterols

The activities of many mammalian membrane proteins including G-protein coupled receptors are cholesterol-dependent. Unlike higher eukaryotes, yeast do not make cholesterol. Rather they make a related molecule called ergosterol. As cholesterol and ergosterol are biologically non-equivalent, the potential of yeast as hosts for overproducing mammalian membrane proteins has never been fully realised. To address this problem, we are trying to engineer a novel strain of Saccharomyces cerevisiae in which the cholesterol biosynthetic pathway of mammalian cells has been fully reconstituted. Thus far, we have created a modified strain that makes cholesterol-like sterols which has an increased capacity to make G-protein coupled receptors compared to control yeast.

Introduction : the role of quality, production and technological innovation in improving competitive performance

Quality, production and technological innovation management rank among the most important matters of concern to modern manufacturing organisations. They can provide companies with the decisive means of gaining a competitive advantage, especially within industries where there is an increasing similarity in product design and manufacturing processes. The papers in this special issue of International Journal of Technology Management have all been selected as examples of how aspects of quality, production and technological innovation can help to improve competitive performance. Most are based on presentations made at the UK Operations Management Association's Sixth International Conference held at Aston University at which the theme was 'Getting Ahead Through Technology and People'. At the conference itself over 80 papers were presented by authors from 15 countries around the world. Among the many topics addressed within the conference theme, technological innovation, quality and production management emerged as attracting the greatest concern and interest of delegates, particularly those from industry. For any new initiative to be implemented successfully, it should be led from the top of the organization. Achieving the desired level of commitment from top management can, however, be a difficulty. In the first paper of this issue, Mackness investigates this question by explaining how systems thinking can help. In the systems approach, properties such as 'emergence', 'hierarchy', 'commnication' and 'control' are used to assist top managers in preparing for change. Mackness's paper is then complemented by Iijima and Hasegawa's contribution in which they investigate the development of Quality Information Management (QIM) in Japan. They present the idea of a Design Review and demonstrate how it can be used to trace and reduce quality-related losses. The next paper on the subject of quality is by Whittle and colleagues. It relates to total quality and the process of culture change within organisations. Using the findings of investigations carried out in a number of case study companies, they describe four generic models which have been identified as characterising methods of implementing total quality within existing organisation cultures. Boaden and Dale's paper also relates to the management of quality, but looks specifically at the construction industry where it has been found there is still some confusion over the role of Quality Assurance (QA) and Total Quality Management (TQM). They describe the results of a questionnaire survey of forty companies in the industry and compare them to similar work carried out in other industries. Szakonyi's contribution then completes this group of papers which all relate specifically to the question of quality. His concern is with the two ways in which R&D or engineering managers can work on improving quality. The first is by improving it in the laboratory, while the second is by working with other functions to improve quality in the company. The next group of papers in this issue all address aspects of production management. Umeda's paper proposes a new manufacturing-oriented simulation package for production management which provides important information for both design and operation of manufacturing systems. A simulation for production strategy in a Computer Integrated Manufacturing (CIM) environment is also discussed. This paper is then followed by a contribution by Tanaka and colleagues in which they consider loading schedules for manufacturing orders in a Material Requirements Planning (MRP) environment. They compare mathematical programming with a knowledge-based approach, and comment on their relative effectiveness for different practical situations. Engstrom and Medbo's paper then looks at a particular aspect of production system design, namely the question of devising group working arrangements for assembly with new product structures. Using the case of a Swedish vehicle assembly plant where long cycle assembly work has been adopted, they advocate the use of a generally applicable product structure which can be adapted to suit individual local conditions. In the last paper of this particular group, Tay considers how automation has affected the production efficiency in Singapore. Using data from ten major industries he identifies several factors which are positively correlated with efficiency, with capital intensity being of greatest interest to policy makers. The two following papers examine the case of electronic data interchange (EDI) as a means of improving the efficiency and quality of trading relationships. Banerjee and Banerjee consider a particular approach to material provisioning for production systems using orderless inventory replenishment. Using the example of a single supplier and multiple buyers they develop an analytical model which is applicable for the exchange of information between trading partners using EDI. They conclude that EDI-based inventory control can be attractive from economic as well as other standpoints and that the approach is consistent with and can be instrumental in moving towards just-in-time (JIT) inventory management. Slacker's complementary viewpoint on EDI is from the perspective of the quality relation-ship between the customer and supplier. Based on the experience of Lucas, a supplier within the automotive industry, he concludes that both banks and trading companies must take responsibility for the development of payment mechanisms which satisfy the requirements of quality trading. The three final papers of this issue relate to technological innovation and are all country based. Berman and Khalil report on a survey of US technological effectiveness in the global economy. The importance of education is supported in their conclusions, although it remains unclear to what extent the US government can play a wider role in promoting technological innovation and new industries. The role of technology in national development is taken up by Martinsons and Valdemars who examine the case of the former Soviet Union. The failure to successfully infuse technology into Soviet enterprises is seen as a factor in that country's demise, and it is anticipated that the newly liberalised economies will be able to encourage greater technological creativity. This point is then taken up in Perminov's concluding paper which looks in detail at Russia. Here a similar analysis is made of the concluding paper which looks in detail at Russia. Here a similar analysis is made of the Soviet Union's technological decline, but a development strategy is also presented within the context of the change from a centralised to a free market economy. The papers included in this special issue of the International Journal of Technology Management each represent a unique and particular contribution to their own specific area of concern. Together, however, they also argue or demonstrate the general improvements in competitive performance that can be achieved through the application of modern principles and practice to the management of quality, production and technological innovation.

Design and implementation of production systems for high variety electronics assembly

Information technology companies are having to broaden their overall strategic view in deference to the premise that it is better to be market-driven than technology-led. Cost and technical performance are no longer the only considerations, as quality and service now demand equal recognition. The production of a high volume single item has given way to that of low volume multiple items, which in turn requires some modification of production systems and brings flexible manufacturing, Just-in-Time production and total quality control into sharper focus for the achievement of corporate objectives.

Modular system design and control for flexible assembly

Flexible Assembly Systems (FASs) are normally associated with the automatic, or robotic, assembly of products, supported by automated material handling systems. However, manual assembly operations are still prevalent within many industries, where the complexity and variety of products prohibit the development of suitable automated assembly equipment. This article presents a generic model for incorporating flexibility into the design and control of assembly operations concerned with high variety/low volume manufacture, drawing on the principles for Flexible Manufacturing Systems (FMS) and Just-in-Time (JIT) delivery. It is based on work being undertaken in an electronics company where the assembly operations have been overhauled and restructured in response to a need for greater flexibility, shorter cycle times and reduced inventory levels. The principles employed are in themselves not original. However, the way they have been combined and tailored has created a total manufacturing control system which represents a new concept for responding to demands placed on market driven firms operating in an uncertain environment.

Setting up a bioreactor for recombinant protein production in yeast

Scale-up from shake flasks to bioreactors allows for the more reproducible, high-yielding production of recombinant proteins in yeast. The ability to control growth conditions through real-time monitoring facilitates further optimization of the process. The setup of a 3-L stirred-tank bioreactor for such an application is described. © 2012 Springer Science+business Media, LLC.

Ash control methods to limit biomass inorganic content and its effect on fast pyrolysis bio-oil stability

This research investigates specific ash control methods to limit inorganic content within biomass prior to fast pyrolysis and effect of specific ash components on fast pyrolysis processing, mass balance yields and bio-oil quality and stability. Inorganic content in miscanthus was naturally reduced over the winter period from June (7.36 wt. %) to February (2.80 wt. %) due to a combination of senescence and natural leaching from rain water. September harvest produced similar mass balance yields, bio-oil quality and stability compared to February harvest (conventional harvest), but nitrogen content in above ground crop was to high (208 kg ha.-1) to maintain sustainable crop production. Deionised water, 1.00% HCl and 0.10% Triton X-100 washes were used to reduce inorganic content of miscanthus. Miscanthus washed with 0.10% Triton X-100 resulted in the highest total liquid yield (76.21 wt. %) and lowest char and reaction water yields (9.77 wt. % and 8.25 wt. % respectively). Concentrations of Triton X-100 were varied to study further effects on mass balance yields and bio-oil stability. All concentrations of Triton X-100 increased total liquid yield and decreased char and reaction water yields compared to untreated miscanthus. In terms of bio-oil stability 1.00% Triton X-100 produced the most stable bio-oil with lowest viscosity index (2.43) and lowest water content index (1.01). Beech wood was impregnated with potassium and phosphorus resulting in lower liquid yields and increased char and gas yields due to their catalytic effect on fast pyrolysis product distribution. Increased potassium and phosphorus concentrations produced less stable bio-oils with viscosity and water content indexes increasing. Fast pyrolysis processing of phosphorus impregnated beech wood was problematic as the reactor bed material agglomerated into large clumps due to char formation within the reactor, affecting fluidisation and heat transfer.

Precision emulsification for droplet and capsule production

Emulsions and microcapsules are typical structures in various dispersion formulations for pharmaceutical, food, personal and house care applications. Precise control over size and size distribution of emulsion droplets and microcapsules are important for effective use and delivery of active components and better product quality. Many emulsification technologies have been developed to meet different formulation and processing requirements. Among them, membrane and microfluidic emulsification as emerging technologies have the feature of being able to precisely manufacture droplets in a drop-by-drop manner to give subscribed sizes and size distributions with lower energy consumption. This paper reviews fundamental sciences and engineering aspects of emulsification, membrane and microfluidic emulsification technologies and their use for precision manufacture of emulsions for intensified processing. Generic application examples are given for single and double emulsions and microcapsules with different structure features. © 2013 The Society of Powder Technology Japan. Published by Elsevier B.V.

Editorial overview:new protein production tools for structural biology

Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.

Cognitive Approach in Castings’ Quality Control

Every year production volume of castings grows, especially grows production volume of non-ferrous metals, thanks to aluminium. As a result, requirements to castings quality also increase. Foundry men from all over the world put all their efforts to manage the problem of casting defects. In this article the authors present an approach based on the use of cognitive models that help to visualize inner cause-and-effect relations leading to casting defects in the foundry process. The cognitive models mentioned comprise a diverse network of factors and their relations, which together thoroughly describe all the details of the foundry process and their influence on the appearance of castings’ defects and other aspects.. Moreover, the article contains an example of a simple die casting model and results of simulation. Implementation of the proposed method will help foundry men reveal the mechanism and the main reasons of casting defects formation.

Serum-free process development:improving the yield and consistency of human mesenchymal stromal cell production

Background aims: The cost-effective production of human mesenchymal stromal cells (hMSCs) for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony-forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter-batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence through a correlation (R² = 0.8705) across all conditions. PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost-effectiveness and reduce the risk in these manufacturing processes.

Oxidised LDL-lipids alter redox ratio, lipid raft formation and increase amyloid beta production by SHSY-5Y cells

Elevated cholesterol in mid-life has been associated with increased risk of dementia in later life. We have previously shown that low density lipoprotein (LDL) is more oxidised in the plasma of dementia patients although total cholesterol levels remained unchanged [1]. We have investigated the hypothesis that amyloid beta production and neurodegeneration can be driven by oxidised lipids derived from LDL following the loss of blood brain barrier integrity with ageing. Therefore, we have investigated amyloid beta formation in SHSY5Y cells treated with LDL, minimally modified (ox) LDL, and lipids extracted from both forms of LDL. LDL-treated SHSY-5Y cell viability was not significantly decreased with up to 8 μg LDL/2 × 104 cells compared to untreated cells. However, 8 μg oxLDL protein/2 × 104 cells decreased the cell viability significantly by 33.7% (P < 0.05). A more significant decrease in cell viability was observed when treating cells with extracted lipids from 8 μg of LDL (by 32.7%; P < 0.01) and oxLDL (by 41%; P < 0.01). In parallel, the ratio of reduced to oxidised GSH was decreased; GSH concentrations were significantly decreased following treatment with 0.8 μg/ml oxLD-L (7.35 ± 0.58;P < 0.01), 1.6 μg/ml (5.27 ± 0.23; P < 0.001) and 4 μg/ml (5.31 ± 0.31; P < 0.001). This decrease in redox potential was associated with an increase acid sphingomyelinase activity and lipid raft formation which could be inhibited by desipramine; SHSY5Y cells treated with oxLDL, and lipids from LDL and oxLDL for 16 h showed significantly increased acid sphingomyelinase activity (5.32 ± 0.35; P < 0.05, 5.21 ± 0.6; P < 0.05, and 5.58 ± 0.44; P < 0.01, respectively) compared to control cells (2.96 ± 0.34). As amyloid beta production is driven by the activity of beta secretase and its association with lipid rafts, we investigated whether lipids from ox-LDL can influence amyloid beta by SHSY-5Y cells in the presence of oxLDL. Using ELISA and Western blot, we confirmed that secretion of amyloid beta oligomers is increased by SHSY-5Y cells in the presence of oxLDL lipids. These data suggest a mechanism whereby LDL, and more significantly oxLDL lipids, can drive amyloid beta production and cytotoxicity in neuronal cells. [1] Li L, Willets RS, Polidori MC, Stahl W, Nelles G, Sies H, Griffiths HR. Oxidative LDL modification is increased in vascular dementia and is inversely associated with cognitive performance. Free Radic Res. 2010 Mar; 44(3): 241–8.

Munkaszervezés a lean termelésben – mit magyaráznak a termelésmenedzsment koncepciók = Work organization in lean production – what production concepts explain

A tanulmány a lean termelés munkaszervezését három termelésmenedzsment koncepció segítségével vizsgálja. Az egyes koncepciók a szervezet eltérő metszeteit érintik: (1) a termék-folyamat mátrix (Hayes és Wheelwright, 1979) a termék és a folyamat jellemzőit helyezi középpontba. A lean hatására a szervezet a mátrixban a nagyobb választék és a folyamat alapú működés (nagyobb függőség) irányába mozdul el. Az elmozdulást üzemi szinten a magas elkötelezettségű munkavégzési rendszer gyakorlatainak bevezetése kíséri, mivel azok támogatják a rugalmas működést, a gyors kommunikációt és problémamegoldást. Az elmozdulás „minősége” és így a munkaszervezési gyakorlatok használata (mélyég, száma, munkavállalók bevonása) nagyban függ a termelési stratégiától és a lean érettségtől. (2) A termelési stratégia szakaszai (Wheelwright és Hayes, 1985) a termelés üzleti stratégiában játszott szerepét elemzik. A lean termelés összeegyeztethető a termelési stratégia harmadik szakaszának „command és control��� szemléletmódjával. Az ilyen lean termelők költégfókuszúak, a hagyományos munkaerőképben gondolkodnak és körükben kevésbé jellemző az új emberi erőforrás gyakorlatok használata. A lean termelés adaptálása ösztönözheti a vállalatokat a termelési stratégia negyedik szintje felé. A negyedik szint a bevonásra, problémamegoldásra és tanulásra épít, amely megfelel a lean „emberek tisztelete” pillérének. (3) A lean érettségi modell (Hines és társai, 2004) a lean szervezeten belüli elmélyülését és terjedését mutatja be. A lean utazás során a vállalatok az eszköz alapú megközelítéstől a komplex értékrendszerben gondolkodó lean szervezet felé haladnak. A technikai tudásanyag egyre szélesebb körűvé válik, ami rávilágít a tudásátadás (személyek közöttire, de akár struktúrákba, folyamatokba építése is) képességének jelentőségére. Az emberi erőforrás gyakorlatok folyamatosan jelennek meg. De csak a legfejlettebb szakasz, a lean tanuló szervezet megjelenése teszi valóban szükségessé a munkavállalói kép újragondolását is. = This paper examines work organization in lean production with the help of three production concepts. These concepts embrace different dimensions of the organization: (1) the product-process matrix (Hayes and Wheelwright, 1979) is about product and process characteristics. Due to the lean the organization shifts within the matrix – towards higher variability and flow (higher level of interdependencies). On the shop floor the shift is accompanied by the introduction of high commitment work system’s practices, since those support flexible operations, fast communication and problem-solving. The „quality” of the shift and hence the application of these work practices (number of practices, their embeddeness, employee involvement) highly depends on manufacturing strategy and lean maturity. (2) The concept of stages of manufacturing strategy (Wheelwright and Hayes, 1985) analyzes the role of the manufacturing function in the business strategy. Lean production is compatible with the „command and control��� approach of the third stage of manufacturing strategy. These lean producers are cost-driven, they have the traditional approach of employees and apply new work organization practices to a less extent. However, the implementation of lean production may drive these companies to the fourth stage. The fourth stage of manufacturing strategy is based on employee involvement, problem-solving and learning. This stage is in full accordance with the „respect for people” pillar of lean production. (3) Lean maturity (Hines et al., 2004) shows the path how lean management deepens and expands within an organization. During the lean journey, companies progress from the tool-based approach to the complex lean value system. The technical knowledge of lean becomes more and more comprehensive and it points out the crucial importance of knowledge conversion capabilities (intrapersonal or even how to build knowledge into structures, processes). Work organization practices constantly appear with the progress, but the review of the traditional approach of employees is only essential at the most advanced stage, when an organization becomes lean learning organization.