328 research outputs found

    Influence of Electric Current on the Liver Parenchyma of the Rat

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    Production and inventory management under multiple resource constraints

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    In this paper we present a model and solution methodology for production and inventory management problems that involve multiple resource constraints. The model formulation is quite general, allowing organizations to handle a variety of multi-item decisions such as determining order quantities, production batch sizes, number of production runs, or cycle times. Resource constraints become necessary to handle interaction among the multiple items. Common types of resource constraints include limits on raw materials, machine capacity, workforce capacity, inventory investment, storage space, or the total number of orders placed. For example, in a production environment, there may be limited workforce capacity and limits on machine capacities for manufacturing various product families. In a purchasing environment where a firm has multiple suppliers, there are often constraints for each supplier, such as the total order from each supplier cannot exceed the volume of the truck. We present efficient algorithms for solving both continuous and integer variable versions of the resource constrained production and inventory management model. The algorithms require the solution of a series of two types of subproblems: one is a nonlinear knapsack problem and the other is a nonlinear problem where the only constraints are lower and upper bounds on the variables. Computational testing of the algorithms is reported and indicates that they are effective for solving large-scale problems

    Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein

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    INTRODUCTION: Hemojuvelin (Hjv) is a key component of the signaling cascade that regulates liver hepcidin (Hamp) expression. The purpose of this study was to determine Hjv protein levels in mice and rats subjected to iron overload and iron deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg); iron deficiency was induced by feeding of an iron-deficient diet, or by repeated phlebotomies. Erythropoietin (EPO)-treated mice were administered recombinant EPO at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg), or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker band of 20 kDa. In mice, the intensity of these bands was not changed following iron injection, repeated bleeding, low iron diet or EPO administration. No change in liver crude membrane Hjv protein was observed in iron-treated or iron-deficient rats. ELISA assay for mouse plasma Hjv did not show significant difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA. DISCUSSION: Since no differences between Hjv protein levels were found following various experimental manipulations of body iron status, the results indicate that, in vivo, substantial changes in Hamp mRNA can occur without noticeable changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin protein content apparently does not represent the limiting step in the control of Hamp gene expression

    Rule-Based Forecasting: Using Judgment in Time-Series Extrapolation

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    Rule-Based Forecasting (RBF) is an expert system that uses judgment to develop and apply rules for combining extrapolations. The judgment comes from two sources, forecasting expertise and domain knowledge. Forecasting expertise is based on more than a half century of research. Domain knowledge is obtained in a structured way; one example of domain knowledge is managers= expectations about trends, which we call “causal forces.” Time series are described in terms of 28 conditions, which are used to assign weights to extrapolations. Empirical results on multiple sets of time series show that RBF produces more accurate forecasts than those from traditional extrapolation methods or equal-weights combined extrapolations. RBF is most useful when it is based on good domain knowledge, the domain knowledge is important, the series is well behaved (such that patterns can be identified), there is a strong trend in the data, and the forecast horizon is long. Under ideal conditions, the error for RBF’s forecasts were one-third less than those for equal-weights combining. When these conditions are absent, RBF neither improves nor harms forecast accuracy. Some of RBF’s rules can be used with traditional extrapolation procedures. In a series of studies, rules based on causal forces improved the selection of forecasting methods, the structuring of time series, and the assessment of prediction intervals

    Golden Rule of Forecasting: Be Conservative

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    This article proposes a unifying theory, or the Golden Rule, or forecasting. The Golden Rule of Forecasting is to be conservative. A conservative forecast is consistent with cumulative knowledge about the present and the past. To be conservative, forecasters must seek out and use all knowledge relevant to the problem, including knowledge of methods validated for the situation. Twenty-eight guidelines are logically deduced from the Golden Rule. A review of evidence identified 105 papers with experimental comparisons; 102 support the guidelines. Ignoring a single guideline increased forecast error by more than two-fifths on average. Ignoring the Golden Rule is likely to harm accuracy most when the situation is uncertain and complex, and when bias is likely. Non-experts who use the Golden Rule can identify dubious forecasts quickly and inexpensively. To date, ignorance of research findings, bias, sophisticated statistical procedures, and the proliferation of big data, have led forecasters to violate the Golden Rule. As a result, despite major advances in evidence-based forecasting methods, forecasting practice in many fields has failed to improve over the past half-century

    Agile manufacturing practices: the role of big data and business analytics with multiple case studies

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    The purpose of this study was to examine the role of big data and business analytics (BDBA) in agile manufacturing practices. Literature has discussed the benefits and challenges related to the deployment of big data within operations and supply chains, but there has not been a study of the facilitating roles of BDBA in achieving an enhanced level of agile manufacturing practices. As a response to this gap, and drawing upon multiple qualitative case studies undertaken among four U.K. organizations, we present and validate a framework for the role of BDBA within agile manufacturing. The findings show that market turbulence has negative universal effects and that agile manufacturing enablers are being progressively deployed and aided by BDBA to yield better competitive and business performance objectives. Further, the level of intervention was found to differ across companies depending on the extent of deployment of BDBA, which accounts for variations in outcomes

    Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors.

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    BACKGROUND: Hepcidin is a major regulator of iron metabolism and plays a key role in anemia of chronic disease, reducing intestinal iron uptake and release from body iron stores. Hypoxia and chemical stabilizers of the hypoxia-inducible transcription factor (HIF) have been shown to suppress hepcidin expression. We therefore investigated the role of HIF in hepcidin regulation. METHODOLOGY/PRINCIPAL FINDINGS: Hepcidin mRNA was down-regulated in hepatoma cells by chemical HIF stabilizers and iron chelators, respectively. In contrast, the response to hypoxia was variable. The decrease in hepcidin mRNA was not reversed by HIF-1alpha or HIF-2alpha knock-down or by depletion of the HIF and iron regulatory protein (IRP) target transferrin receptor 1 (TfR1). However, the response of hepcidin to hypoxia and chemical HIF inducers paralleled the regulation of transferrin receptor 2 (TfR2), one of the genes critical to hepcidin expression. Hepcidin expression was also markedly and rapidly decreased by serum deprivation, independent of transferrin-bound iron, and by the phosphatidylinositol 3 (PI3) kinase inhibitor LY294002, indicating that growth factors are required for hepcidin expression in vitro. Hepcidin promoter constructs mirrored the response of mRNA levels to interleukin-6 and bone morphogenetic proteins, but not consistently to hypoxia or HIF stabilizers, and deletion of the putative HIF binding motifs did not alter the response to different hypoxic stimuli. In mice exposed to carbon monoxide, hypoxia or the chemical HIF inducer N-oxalylglycine, liver hepcidin 1 mRNA was elevated rather than decreased. CONCLUSIONS/SIGNIFICANCE: Taken together, these data indicate that hepcidin is neither a direct target of HIF, nor indirectly regulated by HIF through induction of TfR1 expression. Hepcidin mRNA expression in vitro is highly sensitive to the presence of serum factors and PI3 kinase inhibition and parallels TfR2 expression
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