Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity

It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression.

On the role of magnesium and nitrogen in the infiltration of aluminium by aluminium for rapid prototyping applications

Selective laser sintering has been used to fabricate an aluminium alloy powder preform which is subsequently debound and infiltrated with a second aluminium alloy. This represents a new rapid manufacturing system for aluminium that can be used to fabricate large, intricate parts. The base powder is an alloy such as AA6061. The infiltrant is a binary or higher-order eutectic based on either Al-Cu or At-Si. To ensure that infiltration occurs without loss of dimensional precision, it is important that a rigid skeleton forms prior to infiltration. This can be achieved by the partial transformation of the aluminium to aluminium nitride. In order for this to occur throughout the component, magnesium powder must be added to the alumina support powder which surrounds the part in the furnace. The magnesium scavenges the oxygen and thereby creates a microclimate in which aluminium nitride can form. The replacement of the ionocovalent Al2O3 with the covalent AlN on the surface of the aluminium powders also facilitates wetting and thus spontaneous and complete infiltration. (C) 2004 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The development of hard real-time systems using a formal approach

Hard real-time systems are a class of computer control systems that must react to demands of their environment by providing `correct' and timely responses. Since these systems are increasingly being used in systems with safety implications, it is crucial that they are designed and developed to operate in a correct manner. This thesis is concerned with developing formal techniques that allow the specification, verification and design of hard real-time systems. Formal techniques for hard real-time systems must be capable of capturing the system's functional and performance requirements, and previous work has proposed a number of techniques which range from the mathematically intensive to those with some mathematical content. This thesis develops formal techniques that contain both an informal and a formal component because it is considered that the informality provides ease of understanding and the formality allows precise specification and verification. Specifically, the combination of Petri nets and temporal logic is considered for the specification and verification of hard real-time systems. Approaches that combine Petri nets and temporal logic by allowing a consistent translation between each formalism are examined. Previously, such techniques have been applied to the formal analysis of concurrent systems. This thesis adapts these techniques for use in the modelling, design and formal analysis of hard real-time systems. The techniques are applied to the problem of specifying a controller for a high-speed manufacturing system. It is shown that they can be used to prove liveness and safety properties, including qualitative aspects of system performance. The problem of verifying quantitative real-time properties is addressed by developing a further technique which combines the formalisms of timed Petri nets and real-time temporal logic. A unifying feature of these techniques is the common temporal description of the Petri net. A common problem with Petri net based techniques is the complexity problems associated with generating the reachability graph. This thesis addresses this problem by using concurrency sets to generate a partial reachability graph pertaining to a particular state. These sets also allows each state to be checked for the presence of inconsistencies and hazards. The problem of designing a controller for the high-speed manufacturing system is also considered. The approach adopted mvolves the use of a model-based controller: This type of controller uses the Petri net models developed, thus preservIng the properties already proven of the controller. It. also contains a model of the physical system which is synchronised to the real application to provide timely responses. The various way of forming the synchronization between these processes is considered and the resulting nets are analysed using concurrency sets.

Computer control of machines utilising independent drive mechanisms

The thesis describes an investigation into methods for the specification, design and implementation of computer control systems for flexible manufacturing machines comprising multiple, independent, electromechanically-driven mechanisms. An analysis is made of the elements of conventional mechanically-coupled machines in order that the operational functions of these elements may be identified. This analysis is used to define the scope of requirements necessary to specify the format, function and operation of a flexible, independently driven mechanism machine. A discussion of how this type of machine can accommodate modern manufacturing needs of high-speed and flexibility is presented. A sequential method of capturing requirements for such machines is detailed based on a hierarchical partitioning of machine requirements from product to independent drive mechanism. A classification of mechanisms using notations, including Data flow diagrams and Petri-nets, is described which supports capture and allows validation of requirements. A generic design for a modular, IDM machine controller is derived based upon hierarchy of control identified in these machines. A two mechanism experimental machine is detailed which is used to demonstrate the application of the specification, design and implementation techniques. A computer controller prototype and a fully flexible implementation for the IDM machine, based on Petri-net models described using the concurrent programming language Occam, is detailed. The ability of this modular computer controller to support flexible, safe and fault-tolerant operation of the two intermittent motion, discrete-synchronisation independent drive mechanisms is presented. The application of the machine development methodology to industrial projects is established.

Perceptions of technological change : the attitude of managers towards group technology in the United States food equipment industry

In the center of today's continued and rapid technological change and ever competitive environment of the next millennium, manufacturers must realize that unless they are ready to consider and evaluate new technologies brought onto them, they may fail to adequately respond to the challenges that lie ahead of them. This research was designed to determine the consistency of the perceptions of technical and non-technical administrators, in manufacturing environment, towards technological change and group technology as an advanced manufacturing system. This research has included a review of literature with references to technological change, justification and implementation processes, and various manufacturing systems including group technology and its benefits. This research has used the research method of empirical analysis (quantitative) and case studies (qualitative) to research perceptions of technical and non-technical administrators towards technological change and group technology. Sixty-four (64) technical and fifty-one (51) nontechnical administrators from fifty (50) manufacturing organizations in the United States of America responded to the mail survey questionnaire used in this research. Responses were analyzed using the Repeated Measures ANOVA procedure to compare mean responses of each group. Two correlation analyses, Cronback Coefficient Alpha and Pearson Correlation Coefficient, were also performed to determine the reliability of the questionnaire as well as the degree of correlation of perceptions between these two groups. This research, through the empirical analysis, has found that perceptions of the technical and non-technical administrators towards group technology were not consistent. In other words, they did not perceive the benefits of group technology in the same manner to the overall organizational performance. This finding was significant since it provided the first clear and comprehensive view of the technical and non-technical administrators' perception towards group technology and technological change, in Food Equipment Manufacturer Industry, in United States of America. In addition, a number of cases were analyzed and the results have supported those of the quantitative analysis. Therefore, this research not only has provided basic data, which was unavailable prior to this investigation, but it also provided a basis for future studies.

Cost effectiveness of production control systems

This thesis deals with the problems associated with the planning and control of production, with particular reference to a small aluminium die casting company. The main problem areas were identified as: (a) A need to be able to forecast the customers demands upon the company's facilities. (b) A need to produce a manufacturing programme in which the output of the foundry (or die casting section) was balanced with the available capacity in the machine shop. (c) The need to ensure that the resultant system enabled the company's operating budget to have a reasonable chance of being achieved. At the commencement of the research work the major customers were members of the automobile industry and had their own system of forecasting, from which they issued manufacturing schedules to their component suppliers, The errors in the forecast were analysed and the distributions noted. Using these distributions the customer's forecast was capable of being modified to enable his final demand to be met with a known degree of confidence. Before a manufacturing programme could be developed the actual manufacturing system had to be reviewed and it was found that as with many small companies there was a remarkable lack of formal control and written data. Relevant data with regards to the component and the manufacturing process had therefore to be collected and analysed. The foundry process was fixed but the secondary machining operations were analysed by a technique similar to Component Flow Analysis and as a result the machines were arranged in a series of flow lines. A system of manual production control was proposed and for comparison, a local computer bureau was approached and a system proposed incorporating the production of additional management information. These systems are compared and the relative merits discussed and a proposal made for implementation.

An investigation of production workers' performance variations and the potential impact of attitudes

In most manufacturing systems the contribution of human labour remains a vital element that affects overall performance and output. Workers’ individual performance is known to be a product of personal attitudes towards work. However, in current system design processes, worker performance variability is assumed to be largely insignificant and the potential impact of worker attitudes is ignored. This paper describes a field study that investigated the extent to which workers’ production task cycle times vary and the degree to which such variations are associated with attitude differences. Results show that worker performance varies significantly, much more than is assumed by contemporary manufacturing system designers and that this appears to be due to production task characteristics. The findings of this research and their implications are discussed.

Improving the design process for factories:modelling human performance variation

Theprocess of manufacturing system design frequently includes modeling, and usually, this means applying a technique such as discrete event simulation (DES). However, the computer tools currently available to apply this technique enable only a superficial representation of the people that operate within the systems. This is a serious limitation because the performance of people remains central to the competitiveness of many manufacturing enterprises. Therefore, this paper explores the use of probability density functions to represent the variation of worker activity times within DES models.

A design and implementation methodology for high variety electronics assembly systems

Small indigenous manufacturers of electronic equipment are coming under increasingly severe pressure to adopt a strong defensive position against large multinational and Far Eastern companies. A common response to this threat has been for these firms to adopt a 'market driven' business strategy based on quality and customer service, rather than a 'technology led' strategy which uses technical specification and price to compete. To successfully implement this type of strategy there is a need for production systems to be redesigned to suit the new demands of marketing. Increased range and fast response require economy of scope rather t ban economy or scale while the organisation's culture must promote quality and process consciousness. This paper describes the 'Modular Assembly Cascade' concept which addresses these needs by applying the principles of flexible manufacturing (FMS) and just in time (,JlT) to electronics assembly. A methodology for executing the concept is also outlined. This is called DRAMA (Design Houtirw !'or· Adopting Modular Assembly).

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.

Gestão do sistema de produção e práticas enxutas adotadas nas indústrias paraibanas: um estudo multicaso

The evolution of the practices and strategies of manufacturing management, over the years, has made many companies realign their production systems in order to raise their competitiveness and operational performance. However, in most cases these changes are made in a heterogeneous manner, which ends up leaving the production system without a defined goal, which may end up damaging the managerial strategies of the organization as a whole. Thus, some organizations seek to use techniques and/or successful production practices used by other companies, believing can be able to reproduce the same results. An efficient production system must be fully planned and appropriate to the strategic objectives of the organization. Thus, this paper aims to identify the manufacturing management strategies adopted in paraibanas industries, as well as identify the lean practices used by them. Thus, a qualitative study was conducted, using as methodological basis the multicase study. Were made: direct observations, semi-structured interviews and questionnaires applied to those responsible by the production sector of the participating companies. As a result, it was possible to identify the type of manufacturing management system adopted by companies. Where it was detected that Company A uses a system of Modern Mass Production with focus on productivity and low cost and the Company B is using Lean Manufacturing system focused on quality and diversity. In the two organizations was possible to realize the application of lean practices where the Company what does not use the LM, possessed lean practices in standard extremely mature of utilization.

Análise comparativa das metodologias de remuneração adotadas pelas empresas no Brasil e sua influência na mudança organizacional

Este trabalho foi realizado partindo do pressuposto que os salários e benefícios praticados nas organizações podem influenciar significativamente o desempenho e/ou os resultados empresariais até então apresentados pelas empresas; o que é de extrema importância para empresas que vivenciam um momento de mudança organizacional. Neste contexto, esta pesquisa teve como objetivo principal revisar as metodologias de remuneração de pessoal e, realizar uma análise comparativa das práticas adotadas pelas empresas no Brasil e da sua influência na mudança organizacional. Esta pesquisa teórica e prática foi implementada através da revisão bibliográfica e da pesquisa de campo. Devido ao nível de complexidade do tema em questão foi utilizada a pesquisa exploratória, para melhor verificar como a remuneração influencia no processo de mudança organizacional. Com base em quatro (4) estudos de caso que foram desenvolvidos a partir de uma análise de conteúdo documental e da análise de questionários, observou-se que a remuneração variável é bastante utilizada como complemento do salário base. O resultado deste trabalho leva-nos a conclusão de que as metodologias de remuneração praticadas pelas empresas analisadas neste estudo foram capazes de influenciar positivamente seus resultados, auxiliando a implementação da mudança organizacional.

Scenarios of mentor education in Romania - towards improving teacher induction

The aim of this paper is to examine the induction programme for newly qualified teachers and mentor education in Estonia, providing a comparative analysis of existing Estonian and possible Romanian models of mentoring. While the Estonian induction programme has been in place for more than ten years, induction in Romania is a relatively new and has only been mandatory since 2011 (National Law of Education 1/2011). The specifics of mentor professional development within the Romanian induction framework have yet to be explicated. This paper proposes two possible scenarios suitable for the Romanian system :1) long-term regulated academic education (part of master or doctoral level studies), and 2) flexible short-term in-service education. The advantages and disadvantages of both models are examined and ways to overcome some of the disadvantages are identified. Ultimately, the paper proposes that a flexible, needsdriven system which encompasses a degree of choice will best fulfil the professional development needs of teachers who wish to become mentors. (DIPF/Orig.)

Analysis of competitiveness level in an industrial company using a continuous improvement based approach

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