Multiple order-up-to policy for mitigating bullwhip effect in supply chain network

This paper proposes a multiple order-up-to policy based inventory replenishment scheme to mitigate the bullwhip effect in a multi-stage supply chain scenario, where various transportation modes are available between the supply chain (SC) participants. The proposed policy is similar to the fixed order-up-to policy approach where replenishment decision “how much to order” is made periodically on the basis of the predecided order-up-to inventory level. In the proposed policy, optimal multiple order-up-to levels are assigned to each SC participants, which provides decision making reference point for deciding the transportation related order quantity. Subsequently, a mathematical model is established to define optimal multiple order-up-to levels for each SC participants that aims to maximize overall profit from the SC network. In parallel, the model ensures the control over supply chain pipeline inventory, high satisfaction of customer demand and enables timely utilization of available transportation modes. Findings from the various numerical datasets including stochastic customer demand and lead times validate that—the proposed optimal multiple order-up-to policy based inventory replenishment scheme can be a viable alternative for mitigating the bullwhip effect and well-coordinated SC. Moreover, determining the multiple order-up-to levels is a NP hard combinatorial optimization problem. It is found that the implementation of new emerging optimization algorithm named bacterial foraging algorithm (BFA) has presented superior optimization performances. The robustness and applicability of the BFA algorithm are further validated statistically by employing the percentage heuristic gap and two-way ANOVA analysis

Advanced Techniques for Monitoring, Simulation and Optimization of Machining Processes

In today’s manufacturing industry, pressure for productivity, higher quality and cost saving is heavier than ever. Surviving in today’s highly competitive world is not an easy task, contemporary technology updates and heavy investments are needed in state of the art machinery and modern cutting tool systems. If the machining resources are underutilized, feasible techniques are needed to utilize resources efficiently. The new enhancements in the machine tools sector have enabled opportunities for rapid growth in production rate and high varieties in products in minimum time. But they also raised questions concerning sustainability of exiting manufacturing resources. Buying new machines and tooling lead to huge investments. However, buying new machines and tooling doesn't solve production profitability problems if they are underutilized. In order to find the answer for sustainability of existing manufacturing resources and enhancement of the machining efficiency, researchers are working on finding possible supplementary computer supports. In recent years, the indirect computer supported techniques such as sensor base monitoring and control and virtual machining process simulation have been greatly accepted for real-time decision making, sustainable development and efficient use of machining resources. This thesis work is focused on the development of advanced techniques for monitoring, simulation and optimization of machining processes. The thesis presents the contributions to the development and application of decision support systems for three fundamental aspects of machining processes: 1) Chip form monitoring and process condition monitoring through sensor data clustering and classification. 2) Real time tool wear measurement through tool wear image processing. 3) Machining operation verification and optimization using machining process simulation

Energy oriented multi cutting parameter optimization in face milling

A new model for evaluating the energy consumed by a machine tool for processing a prismatic workpiece was developed. The model takes into account the energy absorbed by different machine components such as the auxiliary systems, the axes, the axes chiller, the tool change system, chip conveyor and the spindle system. The relationships between the power absorption of each considered machine component and the main cutting parameters were adequately modeled. The cutting energy was also taken into consideration. Since the wear of the tool was included in the model, the energy absorbed by the machine during passive phases (e.g. tool changes) was also evaluated. Each machine component model was opportunely configured according to the considered production phase. Some of the parameters of the machine tool energy model were identified through experimental tests performed on a real machining center equipped with linear motors. A multivariable energy optimization was carried out considering the cutting speed, the feed and the radial depth of cut as the main parameters. The energy minimization was performed through exhaustive enumeration methods. Results were properly discussed and analyzed. The optimization analysis was also repeated emulating various machine tool configurations and different production scenarios

Nitric oxide-mediated augmentation of neutrophil reactive oxygen and nitrogen species formation: critical use of probes

Previous reports from this laboratory and others demonstrated NO-mediated biphasic modulation of NADPH oxidase and attenuation of neutrophil reactive oxygen species generation, whereas recently we reported augmentation in DCF fluorescence following NO treatment. These discrepancies seem to be due to utilization of different probes/methods to assess effect of NO on reactive oxygen and nitrogen species (ROS/RNS, reactive species) generation. This study aims to look into this and evaluate NO-mediated enzymatic reactive species formation by using multiple probes, human neutrophils/HL60 cells and various interventions. Addition of NO donor, SNP or SNAP (100 nM-1 mM) to PMNs suspension, exhibited a concentration- and time-dependent augmentation in DCF fluorescence, but reduced DHE fluorescence. Collective generation of reactive species was confirmed by enhanced DMPO-nitrone adduct, dityrosine and rhodamine-123 and quenching of scopoletin. NO also enhanced bacterial killing, without altering phagocytosis. Addition of NO to HL-60 cells lacking functional NADPH oxidase enhanced reactive species formation, indicating importance of other enzyme(s) too. NO-dependent ROS/RNS generation was substantially reduced by NADPH oxidase inhibitor (DPI), MPO inhibitor (ABAH), or NOS inhibitor (7-NI). However, 7-NI reduced MPO activity, warranting reappraisal of those reports, which implied NOS in reactive species formation. The results obtained demonstrated NO-mediated reactive species augmentation in human PMNs. Furthermore, superoxide scavenging by NO seems to be the key process in the decrease of DHE fluorescence and suggest usefulness of DCF as the most appropriate probe to measure the NO-mediated modulation of reactive oxygen species in particular in various pathological situations

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

Previous studies from this laboratory have demonstrated importance of neutrophil-derived nitric oxide (NO) in free radical generation, characterized nitric oxide synthase (NOS) isoforms, and have reported subcellular distribution of NOS in rat peripheral neutrophils. Maximum number of neutrophils are added per day to the circulation from bone marrow, thus neutrophils might add substantial amount of NO in the bone marrow. NO generating ability and NOS isoforms characteristics in bone marrow neutrophil precursor cells is, however, still unexplored. This study was, therefore, undertaken to investigate NO generation ability and the molecular/biochemical characteristics of NOS isoforms in neutrophil precursor cells. The neutrophil precursors were separated on Percoll density gradient and characterized by Giemsa staining, CD markers, and by their size and granularity at various stages of maturation as Bands 1, 2, and 3. Mature neutrophils were efficient in free radical generation and phagocytosis, whereas immature cells had more mitochondria and myeloperoxidase. Amount of NO augmented from immature to mature neutrophils as assessed by fluorescent probe DAF-2DA and Griess reagent. Measurement of NOS enzyme activity further confirmed the functional status of NOS in these cells. NOS isoforms were differentially expressed during neutrophil maturation as confirmed by enzyme activity, Western blotting, flowcytometry, and RT-PCR. Expression of nNOS was predominantly stable in all the stages of neutrophil maturation. iNOS expression was, however, consistently augmented during maturation, whereas eNOS expression was downregulated with neutrophil maturation. Furthermore, all NOS isoforms proteins were distributed in cytosol as well as nucleus as assessed by confocal microscopy. This study for the first time report biochemical and molecular characteristics of NOS isoforms in rat neutrophil precursor cells

Neutrophil extracellular traps contain mitochondrial as well as nuclear DNA and exhibit inflammatory potential

Neutrophils expel extracellular traps (NETs) to entrap and exterminate the invaded micro-organisms. Acute/chronic inflammatory disorders are often observed with aberrantly enhanced NETs formation and high nitric oxide (NO) availability. Recent study from this laboratory demonstrated release of NETs from human neutrophils following treatment with SNP or SNAP. This study is an extension of our previous finding to explore the extracellular bacterial killing, source of DNA in the expelled NETs, their ability to induce proinflammatory cytokines release from platelets/THP-1 cells, and assessment of NO-mediated free radical formation by using a consistent NO donor, DETA-NONOate. NO-mediated NETs exhibited extracellular bacterial killing as determined by colony forming units. NO-mediated NETs formation was due to the activation of NADPH oxidase and myeloperoxidase. NO- or PMA-mediated NETs were positive for both nuclear and mitochondrial DNA as well as proteolytic enzymes. Incubation of NETs with human platelets enhanced the release of IL-1β and IL-8, while with THP-1 cells, release of IL-1β, IL-8, and TNFα was observed. This study demonstrates that NO by augmenting enzymatic free radical generation release NETs to promote extracellular bacterial killing. These NETs were made up of mitochondrial and nuclear DNA and potentiated release of proinflammatory cytokines

Nitric oxide dependent increase in free radical generation mediates release of extracellular traps from human neutrophils

High availability of NO at the inflammatory/infection site is noticed often with oxidative stress and neutrophil extracellular traps (NETs) contents, but role of NO remains unexplored in NETs formation. In the present study incubation of adhered human neutrophils with DETA-NONOate led to NETs release in a time and concentration dependent manner, as assessed by confocal microscopy and by measuring extracellular DNA and NET-bound elastase, which was blocked by N-acetyl cysteine, suggesting role of free radicals. A time and concentration dependent augmentation in free radical formation by NO donors was measured by using DCF-DA, NBT, and by p47 phox migration to the neutrophils membrane. NO mediated formation of NETs and free radicals was significantly attenuated by pretreatment of neutrophils with diphenyleneiodonium, a dual inhibitor of NADPH-oxidase/NO synthase (NOS), 4-aminobenzoic acid hydrazide, a myeloperoxidase inhibitor and 7-nitroindazole, a NOS inhibitor, suggesting enzymatic free radical generation. We thus provide first experimental evidence that NO by augmenting free radical formation in human neutrophils mediates NETs release

Atorvastatin protects against ischemia-reperfusion injury in fructose-induced insulin resistant rats

Purpose: High fructose (HFr) intake is known to cause insulin resistance syndrome (IRS), however its effect against acute coronary events remains elusive. The present study was undertaken to evaluate the effect of HFr (60%) diet on myocardial ischemia-reperfusion (MI-RP) injury and its modulation by atorvastatin treatment. Methods: Wistar rats kept on HFr/chow feeding for 10 weeks, received atorvastatin (30 mg/kg, per oral) or vehicle for two additional weeks followed by MI-RP injury. Results MI-RP injury was significantly augmented in HFr fed rats, as evident by the increase in infarct size (IS, 65±5% vs. 43±7%) and activities of cardiac injury biomarkers [serum lactate dehydrogenase (LDH, 698±57 vs. 444±26 U/L), creatinine kinase (CK-MB, 584±58 vs. 435±28 U/L) and tissue myeloperoxidase (MPO, 235±15 vs. 101±11 µM/min/100 mg tissue)]. Insulin resistance (plasma glucose, 64±5 vs. 100±5 mg/dl; AUC<SUB>0-120 min</SUB>, p&lt;0.05), MI-RP injury (IS 20±5%, LDH 292±28 U/L, CK-MB 257±13 U/L, MPO 95±5 µM/min/100 mg tissue) and triglyceride (TG) level were significantly reduced, while myocardial Akt, p-Akt, eNOS, p-eNOS and iNOS protein expression were significantly enhanced following atorvastatin treatment in comparison to HFr fed rats. Oxidative stress marker, malondialdehyde and circulating levels of inflammatory cytokines (CRP, IL-6, IFN-γ and TNF) were significantly reduced, while total nitrite content in the tissue and plasma was significantly augmented in atorvastatin treated rats. Atorvastatin also ameliorated endothelial dysfunction and significantly enhanced aortic Akt and eNOS protein expression. Conclusion: Atorvastatin conferred significant protection against MI-RP injury and alleviated HFr induced IRS possibly by increasing NOS expression through Akt dependent pathway

Nitric oxide donors release extracellular traps from human neutrophils by augmenting free radical generation

High availability of NO, oxidative stress and neutrophil extracellular trap (NETs) contents are often noticed at the site of inflammation/infection. Studies from this lab and others have reported NO mediated free radical generation from neutrophils; role of NO in NETs formation however remains undefined so far. The present study was therefore undertaken to explore the effect of NO donors on NET release from human neutrophils (PMNs), using confocal/scanning microscopy, measuring the extracellular DNA content and NET-bound elastase activity. Addition of NO donors (SNAP and SNP) to adhered PMNs led to a time and concentration dependent NETs release, which was blocked by N-acetyl cysteine, suggesting involvement of free radicals in NETs formation. Free radical formation by NO donors was assessed by using DCF-DA, DMPO-nitrone antibody and by p47 phox migration to the neutrophils membrane. NO mediated formation of free radicals and NETs was significantly reduced by the pretreatment of neutrophils with diphenyleneiodonium (DPI), a NADPH-oxidase inhibitor and 4-aminobenzoic acid hydrazide (ABAH), a myeloperoxidase inhibitor, suggesting role of enzymatic free radical generation by NO donors. We thus demonstrate that NO by augmenting free radical formation in human neutrophils mediates NETs release