Optimal Structural Results for Assemble-to-Order Generalized M-Systmes

Cataloged from PDF version of article.We consider an assemble-to-order generalized M-system with multiple components and multiple products, batch ordering of components, random lead times, and lost sales. We model the system as an in nite-horizon Markov decision process and seek an optimal control policy, which speci es when a batch of components should be produced and whether an arriving demand for each product should be satis ed. To facilitate our analysis, we introduce new functional characterizations for convexity and submodularity with respect to certain non-unitary directions. These help us characterize optimal inventory replenishment and allocation policies under a mild condition on component batch sizes via a new type of policy: lattice-dependent base-stock and lattice-dependent rationing

Sumoylation is tumor-suppressive and confers proliferative quiescence to hematopoietic progenitors in Drosophila melanogaster larvae

Summary How cell-intrinsic regulation of the cell cycle and the extrinsic influence of the niche converge to provide proliferative quiescence, safeguard tissue integrity, and provide avenues to stop stem cells from giving rise to tumors is a major challenge in gene therapy and tissue engineering. We explore this question in sumoylation-deficient mutants of Drosophila. In wild type third instar larval lymph glands, a group of hematopoietic stem/progenitor cells acquires quiescence; a multicellular niche supports their undifferentiated state. However, how proliferative quiescence is instilled in this population is not understood. We show that Ubc9 protein is nuclear in this population. Loss of the SUMO-activating E1 enzyme, Aos1/Uba2, the conjugating E2 enzyme, Ubc9, or the E3 SUMO ligase, PIAS, results in a failure of progenitors to quiesce; progenitors become hyperplastic, misdifferentiate, and develop into microtumors that eventually detach from the dorsal vessel. Significantly, dysplasia and lethality of Ubc9 mutants are rescued when Ubc9wt is provided specifically in the progenitor populations, but not when it is provided in the niche or in the differentiated cortex. While normal progenitors express high levels of the Drosophila cyclin-dependent kinase inhibitor p21 homolog, Dacapo, the corresponding overgrown mutant population exhibits a marked reduction in Dacapo. Forced expression of either Dacapo or human p21 in progenitors shrinks this population. The selective expression of either protein in mutant progenitor cells, but not in other hematopoietic populations, limits overgrowth, blocks tumorogenesis, and restores organ integrity. We discuss an essential and complex role for sumoylation in preserving the hematopoietic progenitor states for stress response and in the context of normal development of the fly

Experimental Results Indicating Lattice-Dependent Policies May Be Optimal for General Assemble-To-Order Systems

We consider an assemble-to-order (ATO) system with multiple products, multiple components which may be demanded in different quantities by different products, possible batch ordering of components, random lead times, and lost sales. We model the system as an infinite-horizon Markov decision process under the average cost criterion. A control policy specifies when a batch of components should be produced, and whether an arriving demand for each product should be satisfied. Previous work has shown that a lattice-dependent base-stock and lattice-dependent rationing (LBLR) policy is an optimal stationary policy for a special case of the ATO model presented here (the generalized M-system). In this study, we conduct numerical experiments to evaluate the use of an LBLR policy for our general ATO model as a heuristic, comparing it to two other heuristics from the literature: a state-dependent base-stock and state-dependent rationing (SBSR) policy, and a fixed base-stock and fixed rationing (FBFR) policy. Remarkably, LBLR yields the globally optimal cost in each of more than 22,500 instances of the general problem, outperforming SBSR and FBFR with respect to both objective value (by up to 2.6% and 4.8%, respectively) and computation time (by up to three orders and one order of magnitude, respectively) in 350 of these instances (those on which we compare the heuristics). LBLR and SBSR perform significantly better than FBFR when replenishment batch sizes imperfectly match the component requirements of the most valuable or most highly demanded product. In addition, LBLR substantially outperforms SBSR if it is crucial to hold a significant amount of inventory that must be rationed. © 2015 Production and Operations Management Society

The role of the Maternity Liaison Officer in provision of primary health care: A values-based service model

Background: A policy directive of the New South Wales government focused on ensuring that all ethnic groups within the community have appropriate and equitable access to services led to the introduction of the maternity liaison officer (MLO) program in the late 1990s. The role of the MLO is to work alongside health professionals to provide education, social support and counselling to pregnant refugee and migrant women of culturally and linguistically diverse backgrounds (CALD). Methods: We reviewed reports and policy documents from 2008 to examine the attributes of this hospital-based service model and share insights into how the MLOs deliver care to meet the needs of mothers and babies. Findings: Maternity liaison officers have readily assumed the responsibility of maintaining current knowledge and building competency in improving the health and wellbeing of refugee and migrant women and newborns. They act as important bridge between women and the health system enabling vulnerable women to competently navigate their maternity journey, gynaecological care and the care of newborn infants in a culturally sensitive and appropriate manner. Discussion and conclusion: This service model offers an acceptable way to support the delivery of maternity care to women and include those from refugee and CALD- backgrounds. Investment in the rigorous evaluation of this service is needed to provide strong evidence to optimise service delivery and guide future decision making

Monitoring of biomarkers in heart failure.

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF

HuR binding to AU-rich elements present in the 3 ' untranslated region of Classical swine fever virus

Background: Classical swine fever virus (CSFV) is the member of the genus Pestivirus under the family Flaviviridae. The 5' untranslated region (UTR) of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery. The 3' UTR is usually the recognition site of the viral replicase to initiate minus-strand RNA synthesis. Adenosine-uridine rich elements (ARE) are instability determinants present in the 3' UTR of short-lived mRNAs. However, the presence of AREs in the 3' UTR of CSFV conserved in all known strains has never been reported. This study inspects a possible role of the ARE in the 3' UTR of CSFV. Results: Using RNA pull-down and LC/MS/MS assays, this study identified at least 32 possible host factors derived from the cytoplasmic extracts of PK-15 cells that bind to the CSFV 3' UTR, one of which is HuR. HuR is known to bind the AREs and protect the mRNA from degradation. Using recombinant GST-HuR, this study demonstrates that HuR binds to the ARE present in the 3' UTR of CSFV in vitro and that the binding ability is conserved in strains irrespective of virulence. Conclusions: This study identified one of the CSFV 3' UTR binding proteins HuR is specifically binding to in the ARE region

Integration of metal organic frameworks with enzymes as multifunctional solids for cascade catalysis

[EN] Enzymes exhibit a large degree of compatibility with metal-organic frameworks (MOFs) which allows the development of multicomponent catalysts consisting of enzymes adsorbed or occluded by MOFs. The combination of enzymes and MOFs in a multicomponent catalyst can be used to promote cascade reactions in which two or more individual reactions are performed in a single step. Cascade reactions take place due to the cooperation of active sites present on the MOF with the enzyme. A survey of the available data establishes that often an enzyme undergoes stabilization by association with a MOF and the system exhibits notable recyclability. In addition, the existence of synergism is observed as a consequence of the close proximity of all the required active sites in the multicomponent catalyst. After an introductory section describing the specific features and properties of enzyme-MOF assemblies, the main part of the present review focuses on the description of the cascade reactions that have been reported with commercial enzymes associated with MOFs, paying special attention to the advantages derived from the multicomponent catalyst. Related to the catalytic activity to metabolize glucose, generating reactive oxygen species (ROS) and decreasing the solution pH, an independent section describes the recent use of enzyme-MOF catalysts in cancer therapy. The last paragraphs summarize the current state of the art and provide our view on future developments in this field.Financial support by the Spanish Ministry of Science and Innovation (Severo Ochoa and CTQ2018-980237-CO2-1) and Generalitat Valenciana (Prometeo 2017-083) is gratefully acknowledged. A. 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