Dissociation of Oct-1 from the Nuclear Peripheral Structure Induces the Cellular Aging-associated Collagenase Gene Expression

The cellular aging-associated transcriptional repressor that we previously named as Orpheus was identical to Oct-1, a member of the POU domain family. Oct-1 represses the collagenase gene, one of the cellular aging-associated genes, by interacting with an AT-rich cis-element in the upstream of the gene in preimmortalized cells at earlier population-doubling levels and in immortalized cells. In these stages of cells, considerable fractions of the Oct-1 protein were prominently localized in the nuclear periphery and colocalized with lamin B. During the cellular aging process, however, this subspecies of Oct-1 disappeared from the nuclear periphery. The cells lacking the nuclear peripheral Oct-1 protein exhibited strong collagenase expression and carried typical senescent morphologies. Concomitantly, the binding activity and the amount of nuclear Oct-1 protein were reduced in the aging process and resumed after immortalization. However, the whole cellular amounts of Oct-1 protein were not significantly changed during either process. Thus, the cellular aging-associated genes including the collagenase gene seemed to be derepressed by the dissociation of Oct-1 protein from the nuclear peripheral structure. Oct-1 may form a transcriptional repressive apparatus by anchoring nuclear matrix attachment regions onto the nuclear lamina in the nuclear periphery.

Unbinding forces of single antibody-antigen complexes correlate with their thermal dissociation rates

Point mutants of three unrelated antifluorescein antibodies were constructed to obtain nine different single-chain Fv fragments, whose on-rates, off-rates, and equilibrium binding affinities were determined in solution. Additionally, activation energies for unbinding were estimated from the temperature dependence of the off-rate in solution. Loading rate-dependent unbinding forces were determined for single molecules by atomic force microscopy, which extrapolated at zero force to a value close to the off-rate measured in solution, without any indication for multiple transition states. The measured unbinding forces of all nine mutants correlated well with the off-rate in solution, but not with the temperature dependence of the reaction, indicating that the same transition state must be crossed in spontaneous and forced unbinding and that the unbinding path under load cannot be too different from the one at zero force. The distance of the transition state from the ground state along the unbinding pathway is directly proportional to the barrier height, regardless of the details of the binding site, which most likely reflects the elasticity of the protein in the unbinding process. Atomic force microscopy thus can be a valuable tool for the characterization of solution properties of protein-ligand systems at the single molecule level, predicting relative off-rates, potentially of great value for combinatorial chemistry and biology.

Dissociation between changes in cytoplasmic free Ca2+ concentration and insulin secretion as evidenced from measurements in mouse single pancreatic islets.

Simultaneous measurements of cytosolic free Ca2+ concentration and insulin release, in mouse single pancreatic islets, revealed a direct correlation only initially after stimulation with glucose or K+. Later, there is an apparent dissociation between these two parameters, with translocation of alpha and epsilon isoenzymes of protein kinase C to membranes and simultaneous desensitization of insulin release in response to glucose. Recovery of insulin release, without any concomitant changes in cytosolic free Ca2+ concentration, after addition of phorbol 12-myristate 13-acetate, okadaic acid, and forskolin supports the notion that the desensitization process is accounted for by dephosphorylation of key regulatory sites of the insulin exocytotic machinery.

Real time optimization in chemical process: evaluation of strategies, improvements and industrial application.

The increasing economic competition drives the industry to implement tools that improve their processes efficiencies. The process automation is one of these tools, and the Real Time Optimization (RTO) is an automation methodology that considers economic aspects to update the process control in accordance with market prices and disturbances. Basically, RTO uses a steady-state phenomenological model to predict the process behavior, and then, optimizes an economic objective function subject to this model. Although largely implemented in industry, there is not a general agreement about the benefits of implementing RTO due to some limitations discussed in the present work: structural plant/model mismatch, identifiability issues and low frequency of set points update. Some alternative RTO approaches have been proposed in literature to handle the problem of structural plant/model mismatch. However, there is not a sensible comparison evaluating the scope and limitations of these RTO approaches under different aspects. For this reason, the classical two-step method is compared to more recently derivative-based methods (Modifier Adaptation, Integrated System Optimization and Parameter estimation, and Sufficient Conditions of Feasibility and Optimality) using a Monte Carlo methodology. The results of this comparison show that the classical RTO method is consistent, providing a model flexible enough to represent the process topology, a parameter estimation method appropriate to handle measurement noise characteristics and a method to improve the sample information quality. At each iteration, the RTO methodology updates some key parameter of the model, where it is possible to observe identifiability issues caused by lack of measurements and measurement noise, resulting in bad prediction ability. Therefore, four different parameter estimation approaches (Rotational Discrimination, Automatic Selection and Parameter estimation, Reparametrization via Differential Geometry and classical nonlinear Least Square) are evaluated with respect to their prediction accuracy, robustness and speed. The results show that the Rotational Discrimination method is the most suitable to be implemented in a RTO framework, since it requires less a priori information, it is simple to be implemented and avoid the overfitting caused by the Least Square method. The third RTO drawback discussed in the present thesis is the low frequency of set points update, this problem increases the period in which the process operates at suboptimum conditions. An alternative to handle this problem is proposed in this thesis, by integrating the classic RTO and Self-Optimizing control (SOC) using a new Model Predictive Control strategy. The new approach demonstrates that it is possible to reduce the problem of low frequency of set points updates, improving the economic performance. Finally, the practical aspects of the RTO implementation are carried out in an industrial case study, a Vapor Recompression Distillation (VRD) process located in Paulínea refinery from Petrobras. The conclusions of this study suggest that the model parameters are successfully estimated by the Rotational Discrimination method; the RTO is able to improve the process profit in about 3%, equivalent to 2 million dollars per year; and the integration of SOC and RTO may be an interesting control alternative for the VRD process.

A model driven framework for geographic knowledge discovery

Geographic knowledge discovery (GKD) is the process of extracting information and knowledge from massive georeferenced databases. Usually the process is accomplished by two different systems, the Geographic Information Systems (GIS) and the data mining engines. However, the development of those systems is a complex task due to it does not follow a systematic, integrated and standard methodology. To overcome these pitfalls, in this paper, we propose a modeling framework that addresses the development of the different parts of a multilayer GKD process. The main advantages of our framework are that: (i) it reduces the design effort, (ii) it improves quality systems obtained, (iii) it is independent of platforms, (iv) it facilitates the use of data mining techniques on geo-referenced data, and finally, (v) it ameliorates the communication between different users.

Towards a unified framework for opinion retrieval, mining and summarization

The exponential increase of subjective, user-generated content since the birth of the Social Web, has led to the necessity of developing automatic text processing systems able to extract, process and present relevant knowledge. In this paper, we tackle the Opinion Retrieval, Mining and Summarization task, by proposing a unified framework, composed of three crucial components (information retrieval, opinion mining and text summarization) that allow the retrieval, classification and summarization of subjective information. An extensive analysis is conducted, where different configurations of the framework are suggested and analyzed, in order to determine which is the best one, and under which conditions. The evaluation carried out and the results obtained show the appropriateness of the individual components, as well as the framework as a whole. By achieving an improvement over 10% compared to the state-of-the-art approaches in the context of blogs, we can conclude that subjective text can be efficiently dealt with by means of our proposed framework.

Enrichment of the Phenotypic and Genotypic Data Warehouse analysis using Question Answering systems to facilitate the decision making process in cereal breeding programs

Currently there are an overwhelming number of scientific publications in Life Sciences, especially in Genetics and Biotechnology. This huge amount of information is structured in corporate Data Warehouses (DW) or in Biological Databases (e.g. UniProt, RCSB Protein Data Bank, CEREALAB or GenBank), whose main drawback is its cost of updating that makes it obsolete easily. However, these Databases are the main tool for enterprises when they want to update their internal information, for example when a plant breeder enterprise needs to enrich its genetic information (internal structured Database) with recently discovered genes related to specific phenotypic traits (external unstructured data) in order to choose the desired parentals for breeding programs. In this paper, we propose to complement the internal information with external data from the Web using Question Answering (QA) techniques. We go a step further by providing a complete framework for integrating unstructured and structured information by combining traditional Databases and DW architectures with QA systems. The great advantage of our framework is that decision makers can compare instantaneously internal data with external data from competitors, thereby allowing taking quick strategic decisions based on richer data.

A formal framework for modelling complex network management systems

Society today is completely dependent on computer networks, the Internet and distributed systems, which place at our disposal the necessary services to perform our daily tasks. Subconsciously, we rely increasingly on network management systems. These systems allow us to, in general, maintain, manage, configure, scale, adapt, modify, edit, protect, and enhance the main distributed systems. Their role is secondary and is unknown and transparent to the users. They provide the necessary support to maintain the distributed systems whose services we use every day. If we do not consider network management systems during the development stage of distributed systems, then there could be serious consequences or even total failures in the development of the distributed system. It is necessary, therefore, to consider the management of the systems within the design of the distributed systems and to systematise their design to minimise the impact of network management in distributed systems projects. In this paper, we present a framework that allows the design of network management systems systematically. To accomplish this goal, formal modelling tools are used for modelling different views sequentially proposed of the same problem. These views cover all the aspects that are involved in the system; based on process definitions for identifying responsible and defining the involved agents to propose the deployment in a distributed architecture that is both feasible and appropriate.

A Construction Management Framework for Mass Customisation in Traditional Construction

A Mass Customisation model is discussed as a competitive positioning strategy in the marketplace adding value to the customer’s end-use. It includes the user as part of the construction process responding to the customer’s demands and wishes. To the present day, almost all proposals for Mass Customisation have been focused on the design phase and single family houses. The reality is that the processes carried out in the work execution are so inefficient that the costs of the Mass Customisation models are assumed by the customer and they do not offer solutions that support the change management. Furthermore, this inefficiency often makes Mass Customisation unfeasible in terms of deadlines and site management. Therefore, the present proposal focuses on achieving the paradigm of Mass Customisation in the traditional residential construction complementary to the existing proposals in the design phase. All this through the proposal of a framework for the integral management in the work execution, which will address change management introduced by the users offering an efficient and productive model that reduces costs in the process. This model will focus on the synergy between different strategies, techniques and technologies currently used in the construction management (such as Lean Construction or Six Sigma), together with, other strategies and technologies that have proven to be valid solutions in other fields (such as Business Process Management, Service Oriented Architecture, etc.).

Do more with less: a framework for e-government

Dissertação apresentada ao Instituto Politécnico de Castelo Branco para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Desenvolvimento de Software e Sistemas Interactivos, realizada sob a orientação científica do Doutor Arminda Guerra Lopes Professor Doutor do Departamento de Informática do Instituto Politécnico de Castelo Branco

The Dynamic Process of Development through Sport

This article presents a global vision for sport through a new framework that incorporates the elements necessary for a developmentally sound approach to youth sport involvement. This framework proposes that youth sport involvement includes three basic elements: (1) taking part in activities (what), while creating relationships with others (who), in a specific setting (where). When these three elements positively interact, it creates a context that, when repeated on a regular basis, leads to changes in the personal assets of the participants. Changes in individuals’ personal assets, such as Competence, Confidence, Connection, and Character (4 C’s), have long been associated with positive sport experiences, which in turn lead to long-term outcomes, including continued sport Participation, higher levels of Performance in sport, and Personal development through sport (3 P’s). Research linking the three basic elements of youth sport (activities, relationships, and settings) to positive changes in personal assets (4 C’s) and long-term outcomes (3 P’s) are discussed and the Personal Assets Framework is presented

What Does the Lisbon Treaty Change Regarding Subsidiarity within the EU Institutional Framework?

he principle of subsidiarity refers in general to the choice of the most suitable and efficient level for taking policy action. The European Union associates subsidiarity with the way of taking decisions ‘as closely as possible to the citizen’, as it is referred to in the EU treaties. Thus, ensuring the respect of subsidiarity within the EU legislative framework ensures that any EU action is justified when proposing draft legislative acts. The Lisbon Treaty establishes new mechanisms reinforcing subsidiarity control, both ex ante and ex post the EU legislative process, and by doing so, enhances mainly the role of the national parliaments (and to a lesser extent the regional parliaments) and the Committee of the Regions. But in the end, this is a way of ensuring legitimacy of the EU action as it is quite often questioned, especially in times of crisis. Years of practice will tell whether the words will join reality.

Adapting to climate change from a regional perspective: in search of a requisite policy and legal framework. Jean Monnet Occasional Paper No. 8/2014

This paper aims to identify the Mediterranean States’ potential in adopting a regional strategy on climate change adaptation. The author proposes a Mediterranean Strategy on Adaptation to Climate Change as the first step to a political/legal regional approach to climate change issues that would supplement the multilateral process under the United Nations Framework Convention on Climate Change and the Kyoto Protocol. According to the author such a strategy would enhance cooperation between the EU and other Mediterranean states in various ways. The experience of the EU in regulating climate change and its ever growing knowledge-base on its impacts could serve to guide the other Mediterranean states’ and help bridge their knowledge-base gap on the topic. On the other hand, the support and cooperation of the EU’s Mediterranean partners would provide an opportunity for the EU to address better the challenges the climate change threatens to bring in its southernmost regions. The strategy could eventually even pave the way for the very first regional treaty on climate change that could be negotiated under the auspices of the Regional Seas Programme and the Union for the Mediterranean.

Ukraine, Russia and the EU. Breaking the deadlock in the Minsk process. CEPS Working Document No. 423 / June 2016

Although the Minsk process brought about a de-escalation of the conflict in Eastern Ukraine, not all of its 13 points have been implemented, including a ceasefire and withdrawal of heavy weaponry. In the absence of a military option, economic sanctions have become the core instrument of the EU and the US, to respond to Russia’s aggression. At the end of June 2016, when EU Heads of State and Government meet to discuss the extension of sanctions against Russia, they should bear in mind that Russia did not implement the commitments it took upon itself in the framework of the Minsk agreements. Given the persistent deadlock in the Ukraine crisis, the leaders of the EU ought to agree to prolong the sanctions against Russia, push for the renegotiation of the Minsk II agreement and widen the ‘Normandy format’ to include the US and bolster reforms in Ukraine.

Factors influencing the experience of the terminal phase and the grieving process: the primary caregiver’s perspective

Theoretical framework: The experience of the terminal phase and death by patients and caregivers is influenced by multiple factors. This study aimed at understanding this experience from the primary caregiver’s perspective. Objectives: To describe the factors that, from the primary caregiver’s perspective, influenced the experience of disease in the terminal phase and mourning for the death of a close person; To understand the influence of nurses’ conduct on the experience of disease in the terminal phase and mourning for the death of a close person from the primary caregiver’s perspective. Methodology: Qualitative descriptive exploratory study. Results: The following factors were valued: To Assume the Caregiver’s Role, To allow for the end-of-life/terminal phase to take place at home/near the family and Process of Care. Regarding the nurses’ conduct, the knowledge, communication and relationship established by nurses were also valued. Conclusion: In addition to expanding the implementation of specific palliative care teams, the acquisition and development of basic skills in this area by most health care professionals is essential.