Bruna Mota

The Bacterial Protein Azurin Impairs Invasion and FAK/Src Signaling in P-Cadherin-Overexpressing Breast Cancer Cell Models

P-cadherin overexpression occurs in about 30% of all breast carcinomas, being a poor prognostic factor for breast cancer patients. In a cellular background of wild-type E-cadherin, we have previously shown that its expression promotes invasion, motility and migration of breast cancer cells due to the induced secretion of metalloproteases (MMPs) to the extracellular medium and to the concomitant shedding of a pro-invasive soluble form of this protein (sP-cad). Azurin is secreted by Pseudomonas aeruginosa and induces in vitro and in vivo cytotoxicity after its preferential penetration in human cancer cells relative to normal cells. Three different breast cancer cell lines, MCF-7/AZ.Mock, MCF-7/AZ.Pcad and SUM149 were treated with sub-killing doses of azurin. Invasion of these cells was measured using Matrigel Invasion Assays and MTT assays were performed to determine cell viability upon treatment and the effects on cadherins expression was determined by Western blot and Immunofluorescence. Gelatin Zymography was used to determine activity of MMP2 in the conditioned media of azurin treated and untreated cells and the phosphorylation levels of intracellular signaling proteins were determined by Western blot. The invasive phenotype of these breast cancer cells was significantly reduced by azurin. Azurin (50–100 µM) also caused a specific decrease on P-cadherin protein levels from 30–50% in MCF-7/AZ.Pcad and SUM149 breast cancer cell lines, but the levels of E-cadherin remain unaltered. More, the levels of sP-cad and the activity of MMP2 were reduced in the extracellular media of azurin treated cells and we also observed a decrease in the phosphorylation levels of both FAK and Src proteins. Our data show that azurin specifically targets P-cadherin, not E-cadherin, abrogating P-cadherin-mediated invasive effects and signaling. Therefore, azurin could possibly be considered a therapeutic tool to treat poor-prognosis breast carcinomas overexpressing P-cadherin in a wild type E-cadherin context.

Towards supply chain sustainability: balancing costs with environmental and social impacts

This work presents a multi-objective optimization methodology that accounts for economic, environmental and social concerns in a supply chain with reverse flows. Environmental impact assessment is considered through the use of Recipe 2008. A social benefit indicator is developed where the creation of employment in less developed regions is preferred. The multi-objective approach is used to reach a solution of compromise between the three sustainability pillars. The model is applied to a case study developed in collaboration with a Portuguese company, leader in battery production.

Design and Planning of Sustainable Supply Chains

Abstract Supply chains play a significant role in global sustainability as they affect and are affected by several stakeholders, legislation, and cultures. When designing a supply chain it is critical to consider these elements so that a competitive advantage can be achieved in the long run. Simultaneously, governmental institutions need to understand the impact of sustainability measures in the financial performance of the companies. There is then the need to develop decision support tools that can assist in such decisions. However, the complexity, uncertainty, and subjectivity involved in these decisions hamper the development of such tools and literature in the field, as overviewed in this chapter. A multiobjective mixed integer linear programming model is presented with two different environmental and one social metrics being studied. The model is applied to a real case study and important managerial insights are discussed.

Supply chain design and planning accounting for the Triple Bottom Line

Abstract In this work, a multi-objective mixed integer linear programming (moMILP) model is presented for the design and planning of sustainable closed loop supply chains. It includes strategic decisions such as facility location, definition of transportation modes, technology selection and allocation, as well as tactical decisions. The model includes four objectives: 1) The economic pillar, measured through the net present value (NPV); 2) the environmental pillar, which includes Life Cycle Assessment (LCA), through the application of the ReCiPe methodology; 3 and 4) The social pillar measured using two socio-economic indicators applied by the European Union in its Sustainable Development Strategy. The applicability of the model is demonstrated through a representative supply chain case study. Results show that the different objectives influence the supply chain structure and translate in significantly different and conflicting decisions, showing the importance of such type of models to better understand the decisions implications on the different dimensions of sustainability.

Supply Chain Design towards sustainability: Accounting for growth and jobs

Abstract Sustainable supply chain design is nowadays an important topic where not only economic and environmental aspects should be accounted for, but also social aspects are to be considered. A mathematical programming model was developed and a case-study was performed considering two different social indicators: one that prefers facility location in regions of lower GDP and the other in regions of higher unemployment rate. Results show that the outcome depends on the indicator used. However, for the case presented, minimum cost solution also corresponds to a good social solution regarding GDP, which could translate into economic incentives for the company.

Design and Planning of Sustainable Supply Chains: The Case Study of a Tissue Paper Business

While planning to expand its tissue paper business, a Portuguese company aims to explore options regarding the design and planning of its supply chain accounting not only for economic objectives but also environmental and social concerns (the three pillars of sustainability). A multi-objective mixed integer linear programming model (MOMILP) is developed and applied to the company supply chain focusing on the supply of tissue paper to the United Kingdom market. Decisions to be taken include the network structure, entity location and capacity definition, transportation network definition, production and storage levels, and material flow planning. Additionally, it is important to decide whether or not to postpone the conversion to the final product to a location closer to the clients. The augmented epsilon-constraint method is applied to study the trade-off between the three pillars of sustainability and important managerial insights are derived from this study.

Green Supply Chain Design and Planning: The Importance of Decision Integration in Optimization Models

Sustainability is more than ever a central concern when deciding a company’s strategy. Stakeholders are continuously pressuring industries to further reduce their environmental impact. In order to achieve that, it is imperative to look for solutions across all of the company’s operations adopting a supply chain view. However, supply chains’ complexity makes this a challenging task. Analysing the sustainability of such complex systems requires the use of capable tools as are optimization models. Several of these models can be found in the literature, mostly focusing on specific issues or specific decisions in the supply chain. Therefore, a research gap is found in models capable of handling a wider variety of decisions. With this work a mixed integer linear programming model is used to demonstrate the impact of including more or less options/decisions on design and planning decisions, and on the environmental performance of a supply chain. A case-study based on a Portuguese pulp and paper company is analysed. The results obtained for different scenarios are examined.

Sustainable supply chain design and planning: the importance of life cycle scope definition

Abstract Companies are continuously being pressured by governments, customers and NGOs to become environmentally sustainable. In the process industries this is a very important problem since the environmental impacts are often very significant. Although the assessment of the environmental performance of supply chains is becoming a common practice, this topic still remains very challenging for various reasons. One of them is complexity. Supply chains are complex systems, involving several entities, flows, and actors with frequently opposing views and goals. Analysing such system requires the use of powerful tools, such as quantitative models, capable of handling the various logistics variables and contributing to the understanding of their interactions and trade-offs. Such complexity often results in a simplification of several aspects of the environmental analysis, being one the life cycle scope definition. In this work, we address this issue and through the use of a mixed integer linear model we study the extent to which life cycle scope definition influences managerial decisions in the design and planning of complex supply chains. A real case-study in the pulp and paper industry is explored.

The Influence of Corporate Social Responsibility on Economic Performance Within Supply Chain Planning

This work aims to study the economic impact of incorporating corporate social responsibility issues in supply chain design and planning. A mathematical programming model that allows the optimal design and planning of supply chains is developed. A social benefit indicator is established where the regional development of less developed regions is intended. The supply chain is optimized under two different objective functions: economic and social. The model is applied to a case-study developed in collaboration with a Portuguese battery producer.

Green supply chain design and planning

A Mixed Integer Linear Programming model for the design and planning of green supply chains is developed. Strategic and tactical decisions are taken, namely on facility location and capacity installation, supplier selection, technology selection, transportation network definition, supply planning, and product recovery. The aim of this work is to study the use of environmental indicators in these decisions while accounting for profit objectives. Different objective functions concerning environmental aspects are implemented. ReCiPe quantifies the environmental performance of the supply chain and combinations of ReCiPes midpoint categories allow a deeper analysis of the impact of these categories in strategic and tactical decisions. The goal is to understand if focusing on selected categories affects supply chain decisions and overall supply chain environmental impact. Net Present Value quantifies the economic performance and is used for lexicographic optimization. The model is applied to a case-study and important managerial insights are obtained. From a holistic point of view, it answers the question: how should supply chain environmental impact be assessed? From a case-study perspective, insights are obtained regarding what type of improvements should be implemented to reduce the environmental impact and how this would affect supply chain strategic and tactical decisions, along with economic performance.