A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

Two-level network design with intermediate facilities: An application to electrical distribution systems

We consider the two-level network design problem with intermediate facilities. This problem consists of designing a minimum cost network respecting some requirements, usually described in terms of the network topology or in terms of a desired flow of commodities between source and destination vertices. Each selected link must receive one of two types of edge facilities and the connection of different edge facilities requires a costly and capacitated vertex facility. We propose a hybrid decomposition approach which heuristically obtains tentative solutions for the vertex facilities number and location and use these solutions to limit the computational burden of a branch-and-cut algorithm. We test our method on instances of the power system secondary distribution network design problem. The results show that the method is efficient both in terms of solution quality and computational times. (C) 2010 Elsevier Ltd. All rights reserved.

Heuristic optimization of the p-median problem and population re-distribution

This thesis contributes to the heuristic optimization of the p-median problem and Swedish population redistribution.   The p-median model is the most representative model in the location analysis. When facilities are located to a population geographically distributed in Q demand points, the p-median model systematically considers all the demand points such that each demand point will have an effect on the decision of the location. However, a series of questions arise. How do we measure the distances? Does the number of facilities to be located have a strong impact on the result? What scale of the network is suitable? How good is our solution? We have scrutinized a lot of issues like those. The reason why we are interested in those questions is that there are a lot of uncertainties in the solutions. We cannot guarantee our solution is good enough for making decisions. The technique of heuristic optimization is formulated in the thesis.   Swedish population redistribution is examined by a spatio-temporal covariance model. A descriptive analysis is not always enough to describe the moving effects from the neighbouring population. A correlation or a covariance analysis is more explicit to show the tendencies. Similarly, the optimization technique of the parameter estimation is required and is executed in the frame of statistical modeling. 

International strategy: is it meeting the challenge?

The paper proposes an IS process model comprising inputs, development, outputs and a feedback loop based on performance measurement and its interpretation. The feedback impacts on the inputs and development components. Inputs are comprised of market information. human resources, diversity, value creation and host country environmental factors. Development includes preparation and learning. planning and scrutinising partnerships. anticipating impacts of globalisation and experience effects. Outputs comprise structure, scope of operations, target countries. facility location and positioning. Performance interpretation explains rapid and major changes in IS outputs, such as structure and business unit portfolios, whilst process complexity explains observed output similarities for organisations reacting to similar inputs and suggests an evolutionary approach in their determination.

International strategy : is it meeting the challenge?

International strategy (IS) is the approach by which an organisation's capabilities and resources are directed to generate value utilising the global market's opportunities (and risks). Many of the largest multinationals invest significant resources in their IS, however, the literature does not offer any substantive model for the process. This paper presents a model of the IS process which comprises two parts, the first part is made up of inputs, development and outputs and the second comprises a feedback loop based on organisational performance measurement and its interpretation which impacts on the first part stages of inputs and development. The content of the model is explained and justified using examples of practice. Inputs are comprised of market information, human resources, diversity and value creation and host country environmental factors. Development is comprised of preparation and learning, planning and scrutinising partnerships, anticipating impacts of globalisation, anticipating impacts of technology, location, experience effects, planning competencies, planning for cost effectiveness, scenario planning, planning structures and operations, leadership and ethics. Outputs are comprised of structure, scope of operations, target countries, facility location and positioning. Performance interpretation explains rapid and major changes in IS outputs, such as structure
and business unit portfolios, whilst process complexity explains observed output similarities for organisations reacting to similar inputs and suggests an evolutionary approach in their determination.

Proposta de localização de uma unidade de tratamento de óleo e gordura residual de fritura na cidade do Natal/RN para produção de biodiesel

This work addresses biodiesel by transesterification from the use of waste frying oil as a possible technological alternative for both reducing greenhouse gas emissions and by presenting themselves as an environmental call to designate a rational use of oil when no longer played in the environment to become renewable energy. It has proposed location of a residual oil and fat treatment plant to produce biodiesel, using models of Location and Routing for the improvement of routes. To achieve the goal, questionnaires were administered in establishments that use oil or vegetable fat in their productive activities in order to quantify the residue, to analyze actions and environmental perception of people who work directly with the residue on the destination you are being given to oil and fat used. It has indicated using of two single setup location, the method of Center of Gravity and the model of Ardalan, a geographical point that minimizes the costs of transporting waste to the treatment plant. Actions have been proposed for the improvement of collection routes this residue using the Routing Method of Scanning, as an illustration. The results demonstrated the lack of knowledge of the people who deal directly with large amounts of waste, on the environmental impacts caused by their incorrect disposal. The models used were uniform since point out to neighborhoods in similar regions. The neighborhoods of Lagoa Nova / Morro Branco (Ardalan) and Nova Descoberta (Center of Gravity) as ideal for the installation of treatment plant. However, it is suggested to be tested other models that take into account new variables than those used (supply of waste and the distance between points). The routing through the method of scanning has shown that it is possible, in a simple way to optimize routes in order to reduce distances and therefore the logistics costs in the collection of such waste. Introducing a route as a test to gather the twenty largest oil suppliers used in sample frying, using as a main factor time 8 hour of working shift every day

Melhoria da segurança pública: uma proposta para alocação de unidades policiais utilizando o modelo das p-medianas e do caixeiro viajante

The decrease in crime is one of the core issues that cause concern in society today. This study aims to propose improvements to public safety from the choice of points to the location of police units, ie the points which support the car and the police. For this, three models were developed in order to assist decision making regarding the best placement of these bases. The Model of Police Units Routing has the intention to analyze the current configuration of a given region and develop optimal routes for round preventative. The Model of Allocation and Routing for New Police Units (MARNUP) used the model of facility location called p-median weighted and traveling salesman problem (TSP) combined aiming an ideal setting for regions that do not yet have support points or to assess how far the distribution is present in relation to that found in solution. The Model Redefinition and Routing Unit Police (MRRUP) seek to change the current positioning taking into account the budgetary constraints of the decision maker. To verify the applicability of these models we used data from 602 points to instances of police command that is responsible for the capital city of Natal. The city currently has 31 police units for 36 of these 19 districts and police have some assistance. This reality can lead to higher costs and higher response times for answering emergency calls. The results of the models showed that in an ideal situation it is possible to define a distance of 500 km/round, whereas in this 900 km are covered by approximately round. However, a change from three-point lead reduced to 700 km / round which represents a decrease of 22% in the route. This reduction should help improve response time to emergency care, improving the level of service provided by the increase of solved cases, reducing police shifts and routing preventive patrols

Algoritmos para o problema de localização de uma facilidade com distâncias limitadas e restrições de atendimento

The objective in the facility location problem with limited distances is to minimize the sum of distance functions from the facility to the customers, but with a limit on each distance, after which the corresponding function becomes constant. The problem has applications in situations where the service provided by the facility is insensitive after a given threshold distance (eg. fire station location). In this work, we propose a global optimization algorithm for the case in which there are lower and upper limits on the numbers of customers that can be served

Calculating the Best Dual Bound for Problems with Multiple Lagrangian Relaxations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Integração de modelos de localização a sistemas de informações geográficas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Two-level network design with intermediate facilities: An application to electrical distribution systems

We consider the two-level network design problem with intermediate facilities. This problem consists of designing a minimum cost network respecting some requirements, usually described in terms of the network topology or in terms of a desired flow of commodities between source and destination vertices. Each selected link must receive one of two types of edge facilities and the connection of different edge facilities requires a costly and capacitated vertex facility. We propose a hybrid decomposition approach which heuristically obtains tentative solutions for the vertex facilities number and location and use these solutions to limit the computational burden of a branch-and-cut algorithm. We test our method on instances of the power system secondary distribution network design problem. The results show that the method is efficient both in terms of solution quality and computational times. © 2010 Elsevier Ltd.

A priori reformulations for joint rolling-horizon scheduling of materials processing and lot-sizing problem

In many production processes, a key material is prepared and then transformed into different final products. The lot sizing decisions concern not only the production of final products, but also that of material preparation in order to take account of their sequence-dependent setup costs and times. The amount of research in recent years indicates the relevance of this problem in various industrial settings. In this paper, facility location reformulation and strengthening constraints are newly applied to a previous lot-sizing model in order to improve solution quality and computing time. Three alternative metaheuristics are used to fix the setup variables, resulting in much improved performance over previous research, especially regarding the use of the metaheuristics for larger instances. © 2013 Elsevier Ltd. All rights reserved.

Reformulações e relaxação Lagrangiana para o problema de dimensionamento de lotes com várias plantas

Pós-graduação em Matemática - IBILCE

Formulações fortes para o problema de dimensionamento de lotes com várias plantas

This paper considers the multi-plant lot sizing problem. Each item can be produced in any plant and it is possible to meet the demand of a particular plant with production from one (or several) other plants, in this case, incurs a transfer cost. The objective is todevelop strong formulations for this problem. Reformulations that based on the shortest path problem and facility location problem are investigated. Finally, some computational results are presented comparing all the proposed formulations.

Decentralized or centralized production : impacts to the environment, industry, and the economy

Since product take-back is mandated in Europe, and has effects for producers worldwide including the U.S., designing efficient forward and reverse supply chain networks is becoming essential for business viability. Centralizing production facilities may reduce costs but perhaps not environmental impacts. Decentralizing a supply chain may reduce transportation environmental impacts but increase capital costs. Facility location strategies of centralization or decentralization are tested for companies with supply chains that both take back and manufacture products. Decentralized and centralized production systems have different effects on the environment, industry and the economy. Decentralized production systems cluster suppliers within the geographical market region that the system serves. Centralized production systems have many suppliers spread out that meet all market demand. The point of this research is to help further the understanding of company decision-makers about impacts to the environment and costs when choosing a decentralized or centralized supply chain organizational strategy. This research explores; what degree of centralization for a supply chain makes the most financial and environmental sense for siting facilities; and which factories are in the best location to handle the financial and environmental impacts of particular processing steps needed for product manufacture. This research considered two examples of facility location for supply chains when products are taken back; the theoretical case involved shoe resoling and a real world case study considered the location of operations for a company that reclaims multiple products for use as material inputs. For the theoretical example a centralized strategy to facility location was optimal: whereas for the case study a decentralized strategy to facility location was best. In conclusion, it is not possible to say that a centralized or decentralized strategy to facility location is in general best for a company that takes back products. Each company’s specific concerns, needs, and supply chain details will determine which degree of centralization creates the optimal strategy for siting their facilities.