Exact and Approximate Analysis of Multi-Echelon, Multi-Indenture Spare Parts Systems with Commonality

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L-2-hydroxyglutarate production arises from non-canonical enzyme function at acidic pH

The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D(R)- or L(S)- enantiomer, each of which inhibits alpha-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via ‘promiscuous’ reduction of the alternative substrate αKG. Acidic pH enhances production of L-2HG by promoting a protonated form of αKG that binds to a key residue in the substrate-binding pocket of LDHA. Acid-enhanced production of L-2HG leads to stabilization of hypoxia-inducible factor 1 alpha (HIF-1α) in normoxia. These findings offer insights into mechanisms whereby microenvironmental factors influence production of metabolites that alter cell fate and function

Capacity assignment in repair shops with high material uncertainty

We consider a group of identical systems, each consisting of multiple Line Replaceable Units (LRUs) that fail according to a Poisson process. A failed LRU is replaced by a ready-for-use one from a single stock point and, if not available, a backorder cost is incurred per unit of time. The failed LRU is returned to a repair shop, where it is inspected to identify which Shop Replaceable Units (SRUs) caused the failure, and is repaired by replacing the failed SRUs. After repair the LRU is ready-for-use again. Both the LRUs and SRUs are controlled by base stock policies. The repair shop is modeled as a two-stage service process consisting of an inspection and a repair phase. Inspection and repair are executed by one group of repairmen. The repair times depend on the time that elapses between inspection and the repair of a part. We model the total repair capacity as a single server and we compare policies that, based on the repair workload in the repair shop, give priority to either inspection or repair of parts. We suggest two\u3cbr/\u3eapproaches to set the SRU base stock levels, and simulate the system for multiple combinations of the repair workload threshold and predetermined vectors of SRU base stock levels. Based on the simulation results, the LRU base stock levels are optimized. We study a representative setting in which the repair shop faces a high material uncertainty, under different scenarios. We show that a scenario in which we maximize the SRU job completeness, combined with a repair priority policy (in which repair of jobs takes precedence over inspection of jobs) leads to the\u3cbr/\u3elowest total costs

Typology of repair shops for maintenance spare parts

Repair shops for maintenance spare parts have varying levels of complexity and uncertainty when it comes to the capacities and materials required in the repair process. In this paper we outline four type repair shops, based on two dimensions: capacity complexity and material uncertainty. This typology can be used to determine which control principles should be applied to each type of repair shop. In-depth case studies show that all repair shop types exist in practice. From interviews with repair shops managers we found that the perceived complexity to control the repair shops increases as the capacity complexity and/or material uncertainty increases

Connecting inventory control and repair shop control : a differentiated control structure for repairable spare parts

This paper presents a control structure for integrating decisions on spare parts inventory control and the control of repair shops for maintenance spare parts. A dierentiated control structure is proposed for the various repair shop types recognized in practice. Decisions functions are mapped and assigned to either the repair shop manager or the inventory manager. An overview of related literature is presented and open research topics are identied

Connecting inventory and repair shop control for repairable items

\u3cp\u3eThis paper presents control structures for integrating decisions on spare parts inventories and repair shops. A different control structure is proposed for the various repair shop types recognized in practice. An overview of related literature is presented and open research topics are identified. The applicability of the control structures is verified in case studies. This paper furthermore aims to provide a basis for further research on designing control structures for the integrated control of spare parts inventory and repair shops. An agenda for further research is presented.\u3c/p\u3

Gene expression profile in the diaphragm following contractile inactivity during thoracic surgery

Introduction. Recent work revealed the development of marked muscle fiber weakness in the diaphragm, but not in the non-respiratory latissimus dorsi, during thoracic surgery. To disentangle the molecular processes that underlie the development of diaphragm muscle fiber weakness during thoracic surgery, we studied changes in the gene expression profile. Methods. Serial biopsies from the diaphragm and the latissimus dorsi muscle were obtained from four patients during thoracotomy for resection of a tumor in the right lung. Biopsies were taken as soon as the diaphragm had been exposed (t0) and again after two hours (t2). Gobal differences in gene expression in diaphragm biopsies were assessed by microarray analysis. Results. 346 differentially expressed gene transcripts were found in the diaphragm at t2 vs. t0. Pathway analysis revealed that genes associated with inflammation (83 genes; p<0.0001) and cell death (118 genes, p<0.0001) pathways were significantly overexpressed at t2. Of the 346 differentially expressed genes in the diaphragm at t2, 258 were also differential in the latissimus dorsi muscle, with the direction of change being identical for all differentially expressed genes. In addition, latissimus dorsi showed exclusive upregula-ton of negative regulators of cell death. Conclusions. Two hours of thoracic surgery result in rapid and profound changes in expression of inflammatory response and apoptotic genes in the diaphragm. The apoptotic response was stronger in the diaphragm than in the latissiums dorsi. These findings suggest that the development of selective diaphragm muscle fiber weakness in these patients might be related to an exaggerated apoptotic response