Defining the Optimal Inventory Management Program Using Bellman’s Dynamic Programming Method

The paper treats the issue of the Bellman’s dynamic programming defining optimal inventory management program when the delivery and shipment dates are taken into consideration

Nonlocal homogenization for nonlinear metamaterials

©2016 American Physical Society. We present a consistent theoretical approach for calculating effective nonlinear susceptibilities of metamaterials taking into account both frequency and spatial dispersion. Employing the discrete dipole model, we demonstrate that effects of spatial dispersion become especially pronounced in the vicinity of effective permittivity resonance where nonlinear susceptibilities reach their maxima. In that case spatial dispersion may enable simultaneous generation of two harmonic signals with the same frequency and polarization but different wave vectors. We also prove that the derived expressions for nonlinear susceptibilities transform into the known form when spatial dispersion effects are negligible. In addition to revealing new physical phenomena, our results provide useful theoretical tools for analyzing resonant nonlinear metamaterials

Nonlinear symmetry breaking in photometamaterials

© 2018 American Physical Society. We design and analyze theoretically photometamaterials with each meta-atom containing both photodiode and light-emitting diode. Illumination of the photodiode by the light-emitting diode gives rise to an additional optical feedback within each unit cell, which strongly affects resonant properties and nonlinear response of the meta-atom. In particular, we demonstrate that inversion symmetry breaking occurs upon a certain threshold magnitude of the incident wave intensity resulting in an abrupt emergence of second-harmonic generation, which was not originally available, as well as in the reduced third-harmonic signal

Knowledge, Food and Place: a way of producing a way of knowing

The article examines the dynamics of knowledge in the valorisation of local food, drawing on the results from the CORASON project (A cognitive approach to rural sustainable development: the dynamics of expert and lay knowledge), funded by the EU under its Framework Programme 6. It is based on the analysis of several in-depth case studies on food relocalisation carried out in 10 European countries

Preliminary effects of fertilization on ecochemical soil condition in mature spruce stands experiencing dieback in the Beskid Śla̧ski and Żywiecki Mountains, Poland

In recent years, there has been the phenomena of spruce dieback in Europe. Significant areas of spruce low mortality now cover both sides of the Polish southern border. We evaluated ecochemical parameters influencing the heavy dieback occurring in mature spruce stands in the Polish Carpathian Mountains. Dolomite, magnesite and serpentinite fertilizers were applied to experimental plots located in 100-year-old stands in the autumn of 2008. The experimental plots were located in the mid-elevational forest zone (900-950 m) on two nappes of the flysch Carpathians: Magura (Ujsoły Forest District) and Silesian (Wisła Forest District). The saturation of the studied soils demonstrates moderate resilience of soils in Wisła Forest District in relation to acid load and high flexibility of the Ujsoły soils. After application of the fertilizers, an increase of Mg, Ca and Mb was noted in the soil solution, determined in the overlaying highly acidic organic horizons through the ion-exchange buffering mechanism of highly protonated functional groups with high buffering capacity. Magnesium concentration increased following fertilization, presenting a potential improvement of forest growth capacity without the hazard of adverse side effects of liming. Aluminium stress in old spruce is unlikely, while trees in the control plots in Wisła Forest District may already be sensitive to aluminium stress. Serpentinite fertilization improved the supply of soils in magnesium without causing significant changes in the pH of the soil. Such changes in the pH were found in dolomite and magnesite fertilizer. © The Author(s) 2014

Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model

<p>Abstract</p> <p>Objective</p> <p>The phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O₂^-(superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.</p> <p>Materials and Methods and Treatment</p> <p>To clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91<it>^phox</it>-/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models.</p> <p>Results</p> <p>In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).</p

Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo

Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury. Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall

Insights into the Mechanism of Ligand Binding to Octopine Dehydrogenase from Pecten maximus by NMR and Crystallography

Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop, Pecten maximus, catalyzes the NADH dependent, reductive condensation of L-arginine and pyruvate to octopine, NAD+, and water during escape swimming and/or subsequent recovery. The structure of OcDH was recently solved and a reaction mechanism was proposed which implied an ordered binding of NADH, L-arginine and finally pyruvate. Here, the order of substrate binding as well as the underlying conformational changes were investigated by NMR confirming the model derived from the crystal structures. Furthermore, the crystal structure of the OcDH/NADH/agmatine complex was determined which suggests a key role of the side chain of L-arginine in protein cataylsis. Thus, the order of substrate binding to OcDH as well as the molecular signals involved in octopine formation can now be described in molecular detail

Partial Restoration of Mutant Enzyme Homeostasis in Three Distinct Lysosomal Storage Disease Cell Lines by Altering Calcium Homeostasis

A lysosomal storage disease (LSD) results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum–associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil—both US Food and Drug Administration–approved hypertension drugs—partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient–derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely α-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety