TRANSCRIPTIONAL AND POST-TRANSLATIONAL MECHANISMS CONTRIBUTE TO MAINTENANCE OF REST IN NEURAL TUMORS

The RE-1 silencing transcription factor (REST) is an important regulator of normal nervous system development. It negatively regulates neuronal lineage specification in neural progenitors by binding to its consensus RE-1 element(s) located in the regulatory region of its target neuronal differentiation genes. The developmentally coordinated down-regulation of REST mRNA and protein in neural progenitors triggers terminal neurogenesis. REST is overexpressed in pediatric neural tumors such as medulloblastoma and neuroblastoma and is associated with poor neuronal differentiation. High REST protein correlate with poor prognosis for patients with medulloblastoma, however similar studies have not been done with neuroblastoma patients. Mechanism(s) underlying elevated REST levels medulloblastoma and neuroblastoma are unclear, and is the focus of this thesis project. We discovered that transcriptional and post-translational mechanisms govern REST mis-regulation in medulloblastoma and neuroblastoma. In medulloblastoma, REST transcript is aberrantly elevated in a subset of patient samples. Using loss of function and gain of function experiments, we provide evidence that the Hairy Enhancer of Split (HES1) protein represses REST transcription in medulloblastoma cell lines, modulates the expression of neuronal differentiation genes, and alters the survival potential of these cells in vitro. We also show that REST directly represses its own expression in an auto-regulatory feedback loop. Interestingly, our studies identified a novel interaction between REST and HES1. We also observed their co-occupancy at the RE-1 sites, thereby suggesting potential for co-regulation of REST expression. Our pharmacological studies in neuroblastoma using retinoic acid revealed that REST levels are controlled by transcriptional and post-transcriptional mechanisms. Post-transcriptional mechanisms are mediated by modulation of E3 ligase or REST, SCFβ-TRCP, and contribute to resistance of some cells to retinoic acid treatment.

A sea urchin Na+K+2Cl- cotransporter is involved in the maintenance of calcification-relevant cytoplasmic cords in Strongylocentrotus droebachiensis larvae

The cellular mechanisms of calcification in sea urchin larvae are still not well understood. Primary mesenchyme cells within the larval body cavity form a syncytium to secrete CaCO3 spicules from intracellular amorphous CaCO3 (ACC) stores. We studied the role of Na+K+2Cl- cotransporter (NKCC) in intracellular ACC accumulation and larval spicule formation of Strongylocentrotus droebachiensis. First, we incubated growing larvae with three different loop diuretics (azosemide, bumetanide, and furosemide) and established concentration-response curves. All loop diuretics were able to inhibit calcification already at concentrations that specifically inhibit NKCC. Calcification was most effectively inhibited by azosemide (IC50 = 6.5 µM), while larval mortality and swimming ability were not negatively impacted by the treatment. The inhibition by bumetanide (IC50 = 26.4 µM) and furosemide (IC50 = 315.4 µM) resembled the pharmacological fingerprint of the mammalian NKCC1 isoform. We further examined the effect of azosemide on the maintenance of cytoplasmic cords and on the occurrence of calcification vesicles using fluorescent dyes (calcein, FM1-43). Fifty micromolars of azosemide inhibited the maintenance of cytoplasmic cords and resulted in increased calcein fluorescence within calcification vesicles. The expression of NKCC in S. droebachiensis was verified by PCR and Western blot with a specific NKCC antibody. In summary, the pharmacological profile of loop diuretics and their specific effects on calcification in sea urchin larvae suggest that they act by inhibition of NKCC via repression of cytoplasmic cord formation and maintenance.

The asset/liability structure of the Philippine banks and non-bank financial institutions in 2000s : a preliminary study for financial access analyses

Based on the consolidated statements data of the universal/commercial banks (UKbank) and non-bank financial institutions with quasi-banking licenses, this paper presents a keen necessity of obtaining data in detail on both sides (assets and liabilities) of their financial conditions and further analyses. Those would bring more adequate assessments on the Philippine financial system, especially with regard to each financial subsector's financing/lending preferences and behavior. The paper also presents a possibility that the skewed locational and operational distribution exists in the non-UKbank financial subsectors. It suggests there may be a significant deviation from the authorities' (the BSP, SEC and others) intended/anticipated financial system in the banking/non-bank financial institutions' real operations.

Asset composition of the Philippines' universal and commercial banks : monetary policy or self-discipline?

The central bank of the Philippines (Bangko Sentral ng Pilipinas, BSP) has improved its monetary policy measures since the 2000s. After rationalizing the country's banking sector since late-1990s, its monetary policy and the uniiversal/commercial banks' (UCBs) behavior in allocating their assets has changed since mid-2000s. Though further and more detailed studies are nesessary, based on the results of simple correlation analyses conducted in this paper suggest a possible mixture of the country's monetary policy and their own decision-making in asset allocations, instead of a "follow-through" attitude.

A Retrospective View of Software Maintenance and Reengineering Research.

As a summary of past, current, and future trends in software maintenance and reengineering research, we give in this editorial a retrospective look from the past 14 years to now. We provide insight on how software maintenance has evolved and on the most important research topics presented in the series of the European Conference on Software Maintenance and Reengineering.

Design Patterns in Software Maintenance: An Experiment Replication at UPM - Experiences with the RESER'11 Joint Replication Project

Replication of software engineering experiments is crucial for dealing with validity threats to experiments in this area. Even though the empirical software engineering community is aware of the importance of replication, the replication rate is still very low. The RESER'11 Joint Replication Project aims to tackle this problem by simultaneously running a series of several replications of the same experiment. In this article, we report the results of the replication run at the Universidad Politécnica de Madrid. Our results are inconsistent with the original experiment. However, we have identified possible causes for them. We also discuss our experiences (in terms of pros and cons) during the replication.

Application of virtual certification techniques to vehicle design and track maintenance

Virtual certification partially substitutes by computer simulations the experimental techniques required for rail vehicle certification. In this paper, several works were these techniques were used in the vehicle design and track maintenance processes are presented. Dynamic simulation of multibody systems was used to virtually apply the EN14363 standard to certify the dynamic behaviour of vehicles. The works described are: assessment of a freight bogie design adapted to meter-gauge, assessment of a railway track layout for a subway network, freight bogie design with higher speed and axle load, and processing of the data acquired by a track recording vehicle for track maintenance.

Identification of pressures and maintenance in railway tunnels

This paper describes an interactive set of tools used to determine the safety of tunnels and to provide data for the decision making of its mainteinance. Although, no doubt, there are still several drawbacks in the difficult procedures in use it is clear that the way is promising and future improvements both in experimental and analytical methods will increase our understanding of this matter.

A Process Asset Library to support Software Process Improvement in Small Settings

A main factor to the success of any organization process improvement effort is the Process Asset Library implementation that provides a central database accessible by anyone at the organization. This repository includes any process support materials to help process deployment. Those materials are composed of organization's standard software process, software process related documentation, descriptions of the software life cycles, guidelines, examples, templates, and any artefacts that the organization considers useful to help the process improvement. This paper describe the structure and contents of the Web-based Process Asset Library for Small businesses and small groups within large organizations. This library is structured using CMMI as reference model in order to implement those Process Areas described by this model.

Maintenance management model for industrial Smes

This paper presents the design and results of the implementation of a model for the evaluation and improvement of maintenance management in industrial SMEs. A thorough review of the state of the art on maintenance management was conducted to determine the model variables; to characterize industrial SMEs, a questionnaire was developed with Likert variables collected in the previous step. Once validated the questionnaire, we applied the same to a group of seventy-five (75) SMEs in the industrial sector, located in Bolivar State, Venezuela. To identify the most relevant variables maintenance management, we used exploratory factor analysis technique applied to the data collected. The score obtained for all the companies evaluated (57% compliance), highlights the weakness of maintenance management in industrial SMEs, particularly in the areas of planning and continuous improvement; most SMEs are evaluated in corrective maintenance stage, and its performance standard only response to the occurrence of faults.

An Integrated Approach to Strategic Asset Management

This paper focuses on identifying and analysing the elements of Strategic Management for infrastructure and engineering assets. These elements are contended to involve an understanding of governance, corporate policy, corporate objectives, corporate strategy and interagency collaboration and will in turn, allow the ability determine a broader and more comprehensive framework for engineering asset management, ie a ‘staged approach’ to understanding how assets are managed within organisations. While the assets themselves have often been the sole concern for good management practices, other social and contextual elements have come into the mix in order to promote strategic asset management. The development of an integrated approach to asset management is at the base of the research question. What are the considerations and implications for adopting and implementing an integrated strategic asset management (ISAM) framework? While operational matters have been given prominence, a subset of corporate governance, Asset Governance, details the policies and processes needed to acquire, utilise, maintain and account for an organisation’s assets. Asset governance stems from the organisation’s overarching corporate governance principles; as a result it defines the management context in which engineering asset management is implemented. This aspect will be examined to determine the appropriate relationship between organisational strategic management and strategic asset management to further the theoretical engagement with the maturity of strategy,policy and governance for infrastructure and engineered assets. Asset governance stems from the organisation’s overarching corporate governance principles; as a result it defines the management context in which engineering asset management is implemented. The research proceeds by a document analysis of corporate reports and policy recommendations in terms of infrastructure and engineered assets. The paper concludes that incorporating an integrated asset management framework can promote a more robust conceptualisation of public assets and how they combine to provide a comprehensive system of service outcomes.

La responsabilidad social como valor añadido del facilities manager en la gestión del patrimonio inmobiliario

Resulta difícil definir una profesión que surge por la necesidad de adaptar los espacios de trabajo a las nuevas tendencias de las organizaciones, a la productividad, a las nuevas tecnologías que continúan modificando y facilitando desde las últimas décadas el modo y forma de trabajar. Mucho más complicado resulta definir una profesión casi invisible. Cuando todo funciona en un edificio, en un inmueble, en un activo. Todo está correcto. He ahí la dificultad de su definición. Lo que no se ve, no se valora. Las reuniones, las visitas, un puesto de trabajo, una sala de trabajo, una zona de descanso. La climatización, la protección contra incendios, la legionela, el suministro eléctrico, una evacuación. La organización, sus necesidades, su filosofía. Los informes, los análisis, las mejoras. Las personas, el espacio, los procesos, la tecnología. En la actualidad, todo se asocia a su coste. A su rentabilidad. En la difícil tarea de realizar el proyecto de un edificio, participan multitud de aspectos que deben estar perfectamente organizados. El arquitecto proyecta y aúna en el proyecto: pasado (experiencia), presente (tendencias) y futuro (perdurabilidad). Y es en ese momento, cuando al considerar el futuro del edificio, su perdurabilidad, hace que su ciclo de vida sea criterio fundamental al proyectar. Que deba considerarse desde el primer esbozo del proyecto. Para que un edificio perdure en el tiempo existen gran número de factores condicionantes. Empezando por su uso apropiado, su nivel de actividad, pasando por las distintas propiedades que pueda tener, y terminando por los responsables de su mantenimiento en su día a día. Esa profesión invisible, es la disciplina conocida como Facility Management. Otra disciplina no tan novedosa –sus inicios fueron a finales del siglo XIX-, y que en la actualidad se empieza a valorar en gran medida es la Responsabilidad Social. Todo lo que de forma voluntaria, una organización realiza por encima de lo estrictamente legal con objeto de contribuir al desarrollo sostenible (económico, social y medio ambiental). Ambas disciplinas destacan por su continuo dinamismo. Reflejando la evolución de distintas inquietudes: • Personas, procesos, espacios, tecnología • Económica, social, medio-ambiental Y que sólo puede gestionarse con una correcta gestión del cambio. Elemento bisagra entre ambas disciplinas. El presente trabajo de investigación se ha basado en el estudio del grado de sensibilización que existe para con la Responsabilidad Social dentro del sector de la Facility Management en España. Para ello, se han estructurado varios ejercicios con objeto de analizar: la comunicación, el marco actual normativo, la opinión del profesional, del facilities manager. Como objetivo, conocer la implicación actual que la Responsabilidad Social ejerce en el ejercicio de la profesión del Facilities Manager. Se hace especial hincapié en la voluntariedad de ambas disciplinas. De ahí que el presente estudio de investigación realice dicho trabajo sobre elementos voluntarios y por tanto sobre el valor añadido que se obtiene al gestionar dichas disciplinas de forma conjunta y voluntaria. Para que una organización pueda desarrollar su actividad principal –su negocio-, el Facilities Manager gestiona el segundo coste que esta organización tiene. Llegando a poder ser el primero si se incluye el coste asociado al personal (nóminas, beneficios, etc.) Entre el (70 – 80)% del coste de un edificio a lo largo de toda su vida útil, se encuentra en su periodo de explotación. En la perdurabilidad. La tecnología facilita la gestión, pero quien gestiona y lleva a cabo esta perdurabilidad son las personas en los distintos niveles de gestión: estratégico, táctico y operacional. En estos momentos de constante competencia, donde la innovación es el uniforme de batalla, el valor añadido del Facilities Manager se construye gestionando el patrimonio inmobiliario con criterios responsables. Su hecho diferenciador: su marca, su reputación. ABSTRACT It comes difficult to define a profession that emerges due to the need of adapting working spaces to new organization’s trends, productivity improvements and new technologies, which have kept changing and making easier the way that we work during the last decades. Defining an invisible profession results much more complicated than that, because everything is fine when everything works in a building, or in an asset, properly. Hence, there is the difficulty of its definition. What it is not seen, it is not worth. Meeting rooms, reception spaces, work spaces, recreational rooms. HVAC, fire protection, power supply, legionnaire’s disease, evacuation. The organization itself, its needs and its philosophy. Reporting, analysis, improvements. People, spaces, process, technology. Today everything is associated to cost and profitability. In the hard task of developing a building project, a lot of issues, that participate, must be perfectly organized. Architects design and gather/put together in the project: the past (experience), the present (trends) and the future (durability). In that moment, considering the future of the building, e. g. its perdurability, Life Cycle turn as the key point of the design. This issue makes LCC a good idea to have into account since the very first draft of the project. A great number of conditioner factors exist in order to the building resist through time. Starting from a suitable use and the level of activity, passing through different characteristics it may have, and ending daily maintenance responsible. That invisible profession, that discipline, is known as Facility Management. Another discipline, not as new as FM –it begun at the end of XIX century- that is becoming more and more valuable is Social Responsibility. It involves everything a company realizes in a voluntary way, above legal regulations contributing sustainable development (financial, social and environmentally). Both disciplines stand out by their continuous dynamism. Reflecting the evolution of different concerning: • People, process, spaces, technology • Financial, social and environmentally It can only be managed from the right change management. This is the linking point between both disciplines. This research work is based on the study of existing level of increasing sensitivity about Social Responsibility within Facility Management’s sector in Spain. In order to do that, several –five- exercises have been studied with the purpose of analyze: communication, law, professional and facility manager’s opinions. The objective is to know the current implication that Social Responsibility has over Facility Management. It is very important the voluntary part of both disciplines, that’s why the present research work is focused over the voluntary elements and about the added value that is obtained managing the before named disciplines as a whole and in voluntary way. In order a company can develop his core business/primary activities, facility managers must operate the second largest company budget/cost centre. Being the first centre cost if we considerer human resources’ costs included (salaries, incentives…) Among 70-80% building costs are produced along its operative life. Durability Technology ease management, but people are who manage and carry out this durability, within different levels: strategic, tactic and operational. In a world of continuing competence, where innovation is the uniform for the battle, facility manager’s added value is provided managing company’s real estate with responsibility criteria. Their distinguishing element: their brand, their reputation.

Using Electronic Documents for Knowledge Acquisition and Model Maintenance

Knowledge acquisition and model maintenance are key problems in knowledge engineering to improve the productivity in the development of intelligent systems. Although historically a number of technical solutions have been proposed in this area, the recent experience shows that there is still an important gap between the way end-users describe their expertise and the way intelligent systems represent knowledge. In this paper we propose an original way to cope with this problem based on electronic documents. We propose the concept of intelligent document processor as a tool that allows the end-user to read/write a document explaining how an intelligent system operates in such a way that, if the user changes the content of the document, the intelligent system will react to these changes. The paper presents the structure of such a document based on knowledge categories derived from the modern knowledge modeling methodologies together with a number of requirements to be understandable by end-users and problem solvers.

Task-based telemanipulation for maintenance in large scientific facilities

This thesis presents a task-oriented approach to telemanipulation for maintenance in large scientific facilities, with specific focus on the particle accelerator facilities at European Organization for Nuclear Research (CERN) in Geneva, Switzerland and GSI Helmholtz Centre for Heavy Ion Research (GSI) in Darmstadt, Germany. It examines how telemanipulation can be used in these facilities and reviews how this differs from the representation of telemanipulation tasks within the literature. It provides methods to assess and compare telemanipulation procedures as well a test suite to compare telemanipulators themselves from a dexterity perspective. It presents a formalisation of telemanipulation procedures into a hierarchical model which can be then used as a basis to aid maintenance engineers in assessing tasks for telemanipulation, and as the basis for future research. The model introduces a new concept of Elemental Actions as the building block of telemanipulation movements and incorporates the dependent factors for procedures at a higher level of abstraction. In order to gain insight into realistic tasks performed by telemanipulation systems within both industrial and research environments a survey of teleoperation experts is presented. Analysis of the responses is performed from which it is concluded that there is a need within the robotics community for physical benchmarking tests which are geared towards evaluating the dexterity of telemanipulators for comparison of their dexterous abilities. A three stage test suite is presented which is designed to allow maintenance engineers to assess different telemanipulators for their dexterity. This incorporates general characteristics of the system, a method to compare kinematic reachability of multiple telemanipulators and physical test setups to assess dexterity from a both a qualitative perspective and measurably by using performance metrics. Finally, experimental results are provided for the application of the proposed test suite onto two telemanipulation systems, one from a research setting and the other within CERN. It describes the procedure performed and discusses comparisons between the two systems, as well as providing input from the expert operator of the CERN system.

People, management and social responsability. The team: the main asset of any management

People, management and social responsability. The team: the main asset of any management. En colaboración con Dña. Montserrat Castellanos Moreno. Profesora Asociada de la Universidad Europea. Journal of Management and Marketing. Thomson Reuters. Zilina. Slovakia