Embedding of linear programming in a simulated annealing algorithm for solving a mixed integer production planning problem

AbstractThe present paper is concerned with the grouping of book covers on offset plates in order to minimize the total production cost. The mathematical formulation of the problem involves both binary and continuous variables. As exact methods are unable to provide solutions in reasonable time, a heuristic algorithm of the simulated annealing type is proposed. At each iteration, the values of the current solution binary variables are altered in order to yield a neighboring solution. To compute the corresponding values of the continuous variables and the value of the objective function, a linear programming routine is called at each iteration. This constitutes the main originality of the present approach and is in principle applicable in mixed integer programming problems. The procedure is tested on several examples

Effects of Atrazine Exposure on Human Bone Marrow-derived Mesenchymal Stromal Cells Assessed by Combinatorial Assay Matrix

INTRODUCTION: Mesenchymal Stromal/Stem cells (MSCs) are an essential component of the regenerative and immunoregulatory stem cell compartment of the human body and thus of major importance in human physiology. The MSCs elicit their beneficial properties through a multitude of complementary mechanisms, which makes it challenging to assess their phenotype and function in environmental toxicity screening. We here employed the novel combinatorial assays matrix approach/technology to profile the MSC response to the herbicide Atrazine, which is a common environmental xenobiotic, that is in widespread agricultural use in the US and other countries, but banned in the EU. Our here presented approach is representative for screening the impact of environmental xenobiotics and toxins on MSCs as an essential representative component of human physiology and well-being. METHODS: We here employed the combinatorial assay matrix approach, including a panel of well standardized assays, such as flow cytometry, multiplex secretome analysis, and metabolic assays, to define the phenotype and functionality of human-donor-derived primary MSCs exposed to the representative xenobiotic Atrazine. This assay matrix approach is now also endorsed for characterization of cell therapies by leading regulatory agencies, such as FDA and EMA. RESULTS: Our results show that the exposure to Atrazine modulates the metabolic activity, size, and granularity of MSCs in a dose and time dependent manner. Intriguingly, Atrazine exposure leads to a broad modulation of the MSCs secretome (both upregulation and downmodulation of certain factors) with the identification of Interleukin-8 as the topmost upregulated representative secretory molecule. Interestingly, Atrazine attenuates IFNγ-induced upregulation of MHC-class-II, but not MHC-class-I, and early phosphorylation signals on MSCs. Furthermore, Atrazine exposure attenuates IFNγ responsive secretome of MSCs. Mechanistic knockdown analysis identified that the Atrazine-induced effector molecule Interleukin-8 affects only certain but not all the related angiogenic secretome of MSCs. DISCUSSION: The here described Combinatorial Assay Matrix Technology identified that Atrazine affects both the innate/resting and cytokine-induced/stimulated assay matrix functionality of human MSCs, as identified through the modulation of selective, but not all effector molecules, thus vouching for the great usefulness of this approach to study the impact of xenobiotics on this important human cellular subset involved in the regenerative healing responses in humans

Effects of Atrazine exposure on human bone marrow-derived mesenchymal stromal cells assessed by combinatorial assay matrix

IntroductionMesenchymal Stromal/Stem cells (MSCs) are an essential component of the regenerative and immunoregulatory stem cell compartment of the human body and thus of major importance in human physiology. The MSCs elicit their beneficial properties through a multitude of complementary mechanisms, which makes it challenging to assess their phenotype and function in environmental toxicity screening. We here employed the novel combinatorial assays matrix approach/technology to profile the MSC response to the herbicide Atrazine, which is a common environmental xenobiotic, that is in widespread agricultural use in the US and other countries, but banned in the EU. Our here presented approach is representative for screening the impact of environmental xenobiotics and toxins on MSCs as an essential representative component of human physiology and well-being.MethodsWe here employed the combinatorial assay matrix approach, including a panel of well standardized assays, such as flow cytometry, multiplex secretome analysis, and metabolic assays, to define the phenotype and functionality of human-donor-derived primary MSCs exposed to the representative xenobiotic Atrazine. This assay matrix approach is now also endorsed for characterization of cell therapies by leading regulatory agencies, such as FDA and EMA.ResultsOur results show that the exposure to Atrazine modulates the metabolic activity, size, and granularity of MSCs in a dose and time dependent manner. Intriguingly, Atrazine exposure leads to a broad modulation of the MSCs secretome (both upregulation and downmodulation of certain factors) with the identification of Interleukin-8 as the topmost upregulated representative secretory molecule. Interestingly, Atrazine attenuates IFNγ-induced upregulation of MHC-class-II, but not MHC-class-I, and early phosphorylation signals on MSCs. Furthermore, Atrazine exposure attenuates IFNγ responsive secretome of MSCs. Mechanistic knockdown analysis identified that the Atrazine-induced effector molecule Interleukin-8 affects only certain but not all the related angiogenic secretome of MSCs.DiscussionThe here described Combinatorial Assay Matrix Technology identified that Atrazine affects both the innate/resting and cytokine-induced/stimulated assay matrix functionality of human MSCs, as identified through the modulation of selective, but not all effector molecules, thus vouching for the great usefulness of this approach to study the impact of xenobiotics on this important human cellular subset involved in the regenerative healing responses in humans

Robust ordinal regression in preference learning and ranking

Multiple Criteria Decision Aiding (MCDA) offers a diversity of approaches designed for providing the decision maker (DM) with a recommendation concerning a set of alternatives (items, actions) evaluated from multiple points of view, called criteria. This paper aims at drawing attention of the Machine Learning (ML) community upon recent advances in a representative MCDA methodology, called Robust Ordinal Regression (ROR). ROR learns by examples in order to rank a set of alternatives, thus considering a similar problem as Preference Learning (ML-PL) does. However, ROR implements the interactive preference construction paradigm, which should be perceived as a mutual learning of the model and the DM. The paper clarifies the specific interpretation of the concept of preference learning adopted in ROR and MCDA, comparing it to the usual concept of preference learning considered within ML. This comparison concerns a structure of the considered problem, types of admitted preference information, a character of the employed preference models, ways of exploiting them, and techniques to arrive at a final ranking

Etude préliminaire pour l’implémentation d’un dose-banding de chimiothérapie anticancéreuse

« Dose-banding » is a concept of cytotoxic drugs standardization allowing the preparation in advance of standardized rounded doses (SRD) covering the most frequently prescribed doses rounded to ± 5%. Standard doses will be prepared in advance by batch in order to increase production capacity and at the same time to regulate pharmacy workflow as well as to reduce patient waiting time