Graded transcriptional response to different concentrations of a single transactivator

Threshold mechanisms of transcriptional activation are thought to be critical for translating continuous gradients of extracellular signals into discrete all-or-none cellular responses, such as mitogenesis and differentiation. Indeed, unequivocal evidence for a graded transcriptional response in which the concentration of inducer directly correlates with the level of gene expression in individual eukaryotic cells is lacking. By using a novel binary tetracycline regulatable retroviral vector system, we observed a graded rather than a threshold mechanism of transcriptional activation in two different model systems. When polyclonal populations of cells were analyzed at the single cell level, a dose-dependent, stepwise increase in expression of the reporter gene, green fluorescent protein (GFP), was observed by fluorescence-activated cell sorting. These data provide evidence that, in addition to the generally observed all-or-none switch, the basal transcription machinery also can respond proportionally to changes in concentration of extracellular inducers and trancriptional activators.

Memory systems in the brain and localization of a memory

It is now clear that there are a number of different forms or aspects of learning and memory that involve different brain systems. Broadly, memory phenomena have been categorized as explicit or implicit. Thus, explicit memories for experience involve the hippocampus–medial temporal lobe system and implicit basic associative learning and memory involves the cerebellum, amygdala, and other systems. Under normal conditions, however, many of these brain–memory systems are engaged to some degree in learning situations. But each of these brain systems is learning something different about the situation. The cerebellum is necessary for classical conditioning of discrete behavioral responses (eyeblink, limb flexion) under all conditions; however, in the “trace” procedure where a period of no stimuli intervenes between the conditioned stimulus and the unconditioned stimulus the hippocampus plays a critical role. Trace conditioning appears to provide a simple model of explicit memory where analysis of brain substrates is feasible. Analysis of the role of the cerebellum in basic delay conditioning (stimuli overlap) indicates that the memories are formed and stored in the cerebellum. The phenomenon of cerebellar long-term depression is considered as a putative mechanism of memory storage.

Memory systems analyses of mnemonic disorders in aging and age-related diseases

The effects upon memory of normal aging and two age-related neurodegenerative diseases, Alzheimer disease (AD) and Parkinson disease, are analyzed in terms of memory systems, specific neural networks that mediate specific mnemonic processes. An occipital memory system mediating implicit visual-perceptual memory appears to be unaffected by aging or AD. A frontal system that may mediate implicit conceptual memory is affected by AD but not by normal aging. Another frontal system that mediates aspects of working and strategic memory is affected by Parkinson disease and, to a lesser extent, by aging. The aging effect appears to occur during all ages of the adult life-span. Finally, a medial-temporal system that mediates declarative memory is affected by the late onset of AD. Studies of intact and impaired memory in age-related diseases suggest that normal aging has markedly different effects upon different memory systems.

Mapping Binary Liquid-Vapor or Liquid-Liquid-Vapor Equilibria Regions, including the Different Azeotropic Behaviours, as a Function of the NRTL Binary Parameters

13th Mediterranean Congress of Chemical Engineering (Sociedad Española de Química Industrial e Ingeniería Química, Fira Barcelona, Expoquimia), Barcelona, September 30-October 3, 2014

Errors Associated to Keratoconus Grading using Systems based on Corneal Power

Purpose: To analyze and define the possible errors that may be introduced in keratoconus classification when the keratometric corneal power is used in such classification. Materials and methods: Retrospective study including a total of 44 keratoconus eyes. A comprehensive ophthalmologic examination was performed in all cases, which included a corneal analysis with the Pentacam system (Oculus). Classical keratometric corneal power (Pk), Gaussian corneal power (Pc Gauss), True Net Power (TNP) (Gaussian power neglecting the corneal thickness effect), and an adjusted keratometric corneal power (Pkadj) (keratometric power considering a variable keratometric index) were calculated. All cases included in the study were classified according to five different classification systems: Alió-Shabayek, Amsler-Krumeich, Rabinowitz-McDonnell, collaborative longitudinal evaluation of keratoconus (CLEK), and McMahon. Results: When Pk and Pkadj were compared, differences in the type of grading of keratoconus cases was found in 13.6% of eyes when the Alió-Shabayek or the Amsler-Krumeich systems were used. Likewise, grading differences were observed in 22.7% of eyes with the Rabinowitz-McDonnell and McMahon classification systems and in 31.8% of eyes with the CLEK classification system. All reclassified cases using Pkadj were done in a less severe stage, indicating that the use of Pk may lead to the classification of a cornea as keratoconus, being normal. In general, the results obtained using Pkadj, Pc Gauss or the TNP were equivalent. Differences between Pkadj and Pc Gauss were within ± 0.7D. Conclusion: The use of classical keratometric corneal power may lead to incorrect grading of the severity of keratoconus, with a trend to a more severe grading.

Performance of Long-Term Care Systems in Europe. ENEPRI Research Report No. 117, 21 December 2012

This report evaluates the performance of long-term care (LTC) systems in Europe, with a special emphasis on four countries that were selected in Work Package 1 of the ANCIEN project as representative of different LTC systems: Germany, the Netherlands, Spain and Poland. Based on a performance framework, we use the following four core criteria for the evaluation: the quality of life of LTC users, the quality of care, equity of LTC systems and the total burden of LTC (consisting of the financial burden and the burden of informal caregiving). The quality of life is analysed by studying the experience of LTC users in 13 European countries, using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). Older persons with limitations living at home have the highest probability of receiving help (formal or informal) in Germany and the lowest in Poland. Given that help is available, the sufficiency of the help is best ensured in Switzerland, Italy and the Netherlands. The indirectly observed properties of the LTC system are most favourable in France. An older person who considers all three aspects important might be best off living in Belgium or Switzerland. The horizontal and vertical equity of LTC systems are analysed for the four representative countries. The Dutch system scores highest on overall equity, followed by the German system. The Spanish and Polish systems are both less equitable than the Dutch and German systems. To show how ageing may affect the financial burden of LTC, projections until 2060 are given for LTC expenditures for the four representative countries. Under the base scenario, for all four countries the proportions of GDP spent on public and private LTC are projected to more than double between 2010 and 2060, and even treble in some cases. The projections also highlight the large differences in LTC expenditures between the four countries. The Netherlands spends by far the most on LTC. Furthermore, the report presents information for a number of European countries on quality of care, the burden of informal caregiving and other aspects of performance. The LTC systems for the four representative countries are evaluated using the four core criteria. The Dutch system has the highest scores on all four dimensions except the total burden of care, where it has the second-best score after Poland. The German system has somewhat lower scores than the Dutch on all four dimensions. The relatively large role for informal care lowers the equity of the German system. The Polish system excels in having a low total burden of care, but it scores lowest on quality of care and equity. The Spanish system has few extreme scores. Policy implications are discussed in the last chapter of this report and in the Policy Brief based on this report.

Dermal deposition of diazinon on workers using various sheep ectoparasiticide application systems

This study measured the dermal deposition levels of diazinon on workers who apply the ectoparasiticide to sheep using one of five different application systems, namely, portable plunge dipping, fixed plunge dipping, shower dipping, hand jetting, and automatic jetting races. The highest level of dermal exposure occurred while hand jetting and a comparable level occurred in automatic jetting races. The next highest level of dermal exposure was while using the portable and the fixed plunge dipping systems. The shower dipping system appeared to expose workers to the least deposition of diazinon. The variability between the different methods was statistically significant, and the contrast between the three applications using dipping and the two using jetting was highly statistically significant. The variability between testing sessions was too great to allow the methods to be ranked as accurately as the authors would prefer. However, the differences between the methods were large enough to be of practical importance to OHS risk management. (author abstract)

Numerically optimized implementations, mitigation and simulations of polarisation mode dispersion in real-time transmission systems

The aim of this thesis is to present numerical investigations of the polarisation mode dispersion (PMD) effect. Outstanding issues on the side of the numerical implementations of PMD are resolved and the proposed methods are further optimized for computational efficiency and physical accuracy. Methods for the mitigation of the PMD effect are taken into account and simulations of transmission system with added PMD are presented. The basic outline of the work focusing on PMD can be divided as follows. At first the widely-used coarse-step method for simulating the PMD phenomenon as well as a method derived from the Manakov-PMD equation are implemented and investigated separately through the distribution of a state of polarisation on the Poincaré sphere, and the evolution of the dispersion of a signal. Next these two methods are statistically examined and compared to well-known analytical models of the probability distribution function (PDF) and the autocorrelation function (ACF) of the PMD phenomenon. Important optimisations are achieved, for each of the aforementioned implementations in the computational level. In addition the ACF of the coarse-step method is considered separately, based on the result which indicates that the numerically produced ACF, exaggerates the value of the correlation between different frequencies. Moreover the mitigation of the PMD phenomenon is considered, in the form of numerically implementing Low-PMD spun fibres. Finally, all the above are combined in simulations that demonstrate the impact of the PMD on the quality factor (Q=factor) of different transmission systems. For this a numerical solver based on the coupled nonlinear Schrödinger equation is created which is otherwise tested against the most important transmission impairments in the early chapters of this thesis.

Integrating Moodle with University Information Systems

Report published in the Proceedings of the National Conference on "Education in the Information Society", Plovdiv, May, 2013

Integration and querying of heterogeneous, autonomous, distributed database systems

Today, databases have become an integral part of information systems. In the past two decades, we have seen different database systems being developed independently and used in different applications domains. Today's interconnected networks and advanced applications, such as data warehousing, data mining & knowledge discovery and intelligent data access to information on the Web, have created a need for integrated access to such heterogeneous, autonomous, distributed database systems. Heterogeneous/multidatabase research has focused on this issue resulting in many different approaches. However, a single, generally accepted methodology in academia or industry has not emerged providing ubiquitous intelligent data access from heterogeneous, autonomous, distributed information sources. ^ This thesis describes a heterogeneous database system being developed at High-performance Database Research Center (HPDRC). A major impediment to ubiquitous deployment of multidatabase technology is the difficulty in resolving semantic heterogeneity. That is, identifying related information sources for integration and querying purposes. Our approach considers the semantics of the meta-data constructs in resolving this issue. The major contributions of the thesis work include: (i) providing a scalable, easy-to-implement architecture for developing a heterogeneous multidatabase system, utilizing Semantic Binary Object-oriented Data Model (Sem-ODM) and Semantic SQL query language to capture the semantics of the data sources being integrated and to provide an easy-to-use query facility; (ii) a methodology for semantic heterogeneity resolution by investigating into the extents of the meta-data constructs of component schemas. This methodology is shown to be correct, complete and unambiguous; (iii) a semi-automated technique for identifying semantic relations, which is the basis of semantic knowledge for integration and querying, using shared ontologies for context-mediation; (iv) resolutions for schematic conflicts and a language for defining global views from a set of component Sem-ODM schemas; (v) design of a knowledge base for storing and manipulating meta-data and knowledge acquired during the integration process. This knowledge base acts as the interface between integration and query processing modules; (vi) techniques for Semantic SQL query processing and optimization based on semantic knowledge in a heterogeneous database environment; and (vii) a framework for intelligent computing and communication on the Internet applying the concepts of our work. ^

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.

Integration and querying of heterogeneous, autonomous, distributed database systems

Today, databases have become an integral part of information systems. In the past two decades, we have seen different database systems being developed independently and used in different applications domains. Today's interconnected networks and advanced applications, such as data warehousing, data mining & knowledge discovery and intelligent data access to information on the Web, have created a need for integrated access to such heterogeneous, autonomous, distributed database systems. Heterogeneous/multidatabase research has focused on this issue resulting in many different approaches. However, a single, generally accepted methodology in academia or industry has not emerged providing ubiquitous intelligent data access from heterogeneous, autonomous, distributed information sources. This thesis describes a heterogeneous database system being developed at Highperformance Database Research Center (HPDRC). A major impediment to ubiquitous deployment of multidatabase technology is the difficulty in resolving semantic heterogeneity. That is, identifying related information sources for integration and querying purposes. Our approach considers the semantics of the meta-data constructs in resolving this issue. The major contributions of the thesis work include: (i.) providing a scalable, easy-to-implement architecture for developing a heterogeneous multidatabase system, utilizing Semantic Binary Object-oriented Data Model (Sem-ODM) and Semantic SQL query language to capture the semantics of the data sources being integrated and to provide an easy-to-use query facility; (ii.) a methodology for semantic heterogeneity resolution by investigating into the extents of the meta-data constructs of component schemas. This methodology is shown to be correct, complete and unambiguous; (iii.) a semi-automated technique for identifying semantic relations, which is the basis of semantic knowledge for integration and querying, using shared ontologies for context-mediation; (iv.) resolutions for schematic conflicts and a language for defining global views from a set of component Sem-ODM schemas; (v.) design of a knowledge base for storing and manipulating meta-data and knowledge acquired during the integration process. This knowledge base acts as the interface between integration and query processing modules; (vi.) techniques for Semantic SQL query processing and optimization based on semantic knowledge in a heterogeneous database environment; and (vii.) a framework for intelligent computing and communication on the Internet applying the concepts of our work.

Holocene precipitation change in different monsoon sub-regions (time-slices and transient data) simulated by different global climate models, with links to model results

The recently proposed global monsoon hypothesis interprets monsoon systems as part of one global-scale atmospheric overturning circulation, implying a connection between the regional monsoon systems and an in-phase behaviour of all northern hemispheric monsoons on annual timescales (Trenberth et al., 2000). Whether this concept can be applied to past climates and variability on longer timescales is still under debate, because the monsoon systems exhibit different regional characteristics such as different seasonality (i.e. onset, peak, and withdrawal). To investigate the interconnection of different monsoon systems during the pre-industrial Holocene, five transient global climate model simulations have been analysed with respect to the rainfall trend and variability in different sub-domains of the Afro-Asian monsoon region. Our analysis suggests that on millennial timescales with varying orbital forcing, the monsoons do not behave as a tightly connected global system. According to the models, the Indian and North African monsoons are coupled, showing similar rainfall trend and moderate correlation in rainfall variability in all models. The East Asian monsoon changes independently during the Holocene. The dissimilarities in the seasonality of the monsoon sub-systems lead to a stronger response of the North African and Indian monsoon systems to the Holocene insolation forcing than of the East Asian monsoon and affect the seasonal distribution of Holocene rainfall variations. Within the Indian and North African monsoon domain, precipitation solely changes during the summer months, showing a decreasing Holocene precipitation trend. In the East Asian monsoon region, the precipitation signal is determined by an increasing precipitation trend during spring and a decreasing precipitation change during summer, partly balancing each other. A synthesis of reconstructions and the model results do not reveal an impact of the different seasonality on the timing of the Holocene rainfall optimum in the different sub-monsoon systems. They rather indicate locally inhomogeneous rainfall changes and show, that single palaeo-records should not be used to characterise the rainfall change and monsoon evolution for entire monsoon sub-systems.

Model based integration of management systems (MSs) – case study

Abstract Purpose – The purpose of this paper is to present a case study regarding the deployment of a previously developed model for the integration of management systems (MSs). The case study is developed at a manufacturing site of an international enterprise. The implementation of this model in a real business environment is aimed at assessing its feasibility. Design/methodology/approach – The presented case study takes into account different management systems standards (MSSs) progressively implemented, along the years, independently. The implementation of the model was supported by the results obtained from an investigation performed according to a structured diagnosis that was conducted to collect information related to the organizational situation of the enterprise. Findings – The main findings are as follows: a robust integrated management system (IMS), objectively more lean, structured and manageable was found to be feasible; this study provided an holistic view of the enterprise’s global management; clarifications of job descriptions and boundaries of action and responsibilities were achieved; greater efficiency in the use of resources was attained; more coordinated management of the three pillars of sustainability – environmental, economic and social, as well as risks, providing confidence and added value to the company and interested parties was achieved. Originality/value – This case study is pioneering in Portugal in respect to the implementation, at the level of an industrial organization, of the model previously developed for the integration of individualized MSs. The case study provides new insights regarding the implementation of IMSs including the rationalization of several resources and elimination of several types of organizational waste leveraging gains of efficiency. Due to its intrinsic characteristics, the model is able to support, progressively, new or revised MSSs according to the principles of annex SL (normative) – proposals for MSSs – of the International Organization for Standardization and the International Electrotechnical Commission, that the industrial organization can adopt beyond the current ones.

Protocolos para a colocação e remoção de espigões

A utilização de espigões em dentes tratados endodonticamente é um dos temas mais estudados em Medicina Dentária. As opiniões são divergentes em relação aos procedimentos clínicos e materiais a serem utilizados para a colocação e remoção de espigões. O objetivo deste trabalho foi realizar uma revisão bibliográfica de forma a organizar conceitos e princípios clínicos para melhor esclarecer os fatores que determinam a necessidade de colocação, utilização e escolha do tipo de espigão, sua cimentação e técnicas para a remoção. Foram analisadas as características e propriedades dos cimentos de fosfato de zinco, ionômero de vidro, cimentos resinosos de polimerização química, polimerização dupla, foto-polimerizável e os sistemas adesivos etch and rinse, self etch e autoadesivos, bem como as técnicas para a remoção de espigões cimentados com diferentes cimentos e sistemas adesivos para depois acessar o remanescente de guta percha para o retratamento endodôntico. Foi feita uma pesquisa bibliográfica na base de dados electrónica PubMed, Google Scholar e RCAAP com as seguintes palavras chave: “Espigões”; “Retratamento Endodôntico”; “Ionómero de Vidro”; “Fosfato de Zinco”; “Cimentos Resinosos”; “Posts”; “Endodontic Retreatment”; “Glass Ionomer”; Zinc-phosphate”; “Resin Cements"; “Push Out Test”; “Posts AND Removal”. Concluiu-se que a cimentação de espigões pré-fabricados de fibra de vidro com cimentos resinosos de dupla polimerização associados aos sistemas adesivos self etch estão gradualmente substituindo os outros tipos de espigões e demais cimentos e possibilitam restaurar o dente de forma adequada e duradoura. E o uso de ultrassons apresenta maior eficácia e segurança na remoção dos espigões.