A decision-making approach for investigating the potential effects of near sourcing on supply chain

Purpose - Near sourcing is starting to be regarded as a valid alternative to global sourcing in order to leverage supply chain (SC) responsiveness and economic efficiency. The present work proposes a decision-making approach developed in collaboration with a leading Italian retailer that was willing to turn the global store furniture procurement process into near sourcing. Design/methodology/approach - Action research is employed. The limitations of the traditional SC organisation and purchasing process of the company are first identified. On such basis, an inventory management model is applied to run spreadsheet estimates where different purchasing and SC management strategies are adopted to determine the solution providing the lowest cost performance. Finally, a risk analysis of the selected best SC arrangement is conducted and results are discussed. Findings - Switching from East Asian suppliers to continental vendors enables a SC reengineering that increases flexibility and responsiveness to demand uncertainty which, together with decreased transportation costs, assures economic viability, thus proving the benefits of near sourcing. Research limitations/implications - The decision-making framework provides a methodological roadmap to address the comparison between near and global sourcing policies and to calculate the savings of the former against the latter. The approach could include additional organisational aspects and cost categories impacting on near sourcing and could be adapted to investigate different products, services, and business sectors. Originality/value - The work provides SC researchers and practitioners with a structured approach for understanding what drives companies to adopt near sourcing and for quantitatively assessing its advantage

Platelet-activating factor enhances complement-dependent phagocytosis of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1).

Oligomerization of band 3 protein has been recently indicated as an early event in senescent or damaged red cell membrane followed by specific deposition of anti-band 3 antibodies and binding of complement C3 fragments. The band 3-anti-band 3-C3b complex is recognized by homologous monocytes, and phagocytosis ensues. This study shows that recognition of the anti-band 3-C3b complex by the monocyte C3b receptor type one (CR1) plays a crucial role in the process of removal of damaged red cells. Indeed, blocking of monocyte CR1 with an anti-CR1 monoclonal antibody abrogated phagocytosis of diamide-treated red cells. Platelet-activating factor (PAF) is a phospholipid mediator involved in inflammatory processes. Nanomolar (R)-PAF enhanced the CR1-dependent phagocytosis of diamide-treated human red cell and of sheep red cells coated with C3b, induced the fast translocation of protein kinase C to monocyte membrane compartment, and stimulated the phosphorylation of monocyte CR1. The biologically inert lyso-PAF and the enantiomer (S)-PAF were inactive. PAF receptor antagonists and inhibitors of protein kinase C blocked the enhancement of phagocytosis induced by PAF. Protein kinase C translocation, phosphorylation of CR1, and stimulation of this receptor to an active state capable of mediating phagocytosis represent a novel pathway by which PAF interferes with red cell homeostasis and possibly modulates inflammatory reactions and host mechanisms against infections

Climate control on sulphate and nitrate concentrations in alpine streams of Northern Italy along a nitrogen saturation gradient

International audienceThe role of meteorology, hydrology and atmospheric deposition on the temporal pattern of SO4 and NO3 concentrations was investigated for three streams draining alpine catchments in Northern Italy. The study sites lie on a gradient of atmospheric fluxes of SO4 and NO3 (from about 50 to 80 meq m?2 y?1, and from 40 to 90 meq m?2 y?1, respectively). As a consequence of the increasing N input, the three catchments are also representative of aggrading levels of N saturation. Different methods of statistical analysis were applied to monthly data for the period 1997?2005 to identify which variables (temperature, precipitation, hydrology, SO4 and NO3 deposition) were the main predictors of water chemistry and its change in time. Hydrological changes and snow cover proved to be the main confounding factors in the response to atmospheric deposition in the River Masino catchment. Its particular characteristics (small catchment area, rapid flushing during runoff and thin soil cover) meant that this site responded without a significant delay to SO4 deposition decrease. It also showed a clear seasonal pattern of NO3 concentration, in response to hydrology and biological uptake in the growing season. The selected driving variables failed to model the water chemistry at the other study sites. Nevertheless, temperature, especially extreme values, turned out to be important in both SO4 and NO3 export from the catchments. This result might be largely explained by the effect of warm periods on temperature-dependent processes such as mineralization, nitrification and S desorption. Our findings suggest that surface waters in the alpine area will be extremely sensitive to a climate warming scenario: higher temperatures and increasing frequency of drought could exacerbate the effects of high chronic N deposition

Two-fluid and magnetohydrodynamic modelling of magnetic reconnection in the MAST spherical tokamak and the solar corona

Twisted magnetic flux ropes are ubiquitous in space and laboratory plasmas, and the merging of such flux ropes through magnetic reconnection is an important mechanism for restructuring magnetic fields and releasing free magnetic energy. The merging-compression scenario is one possible start up scheme for spherical tokamaks, which has been used on the Mega Amp Spherical Tokamak MAST. Two current-carrying plasma rings, or flux ropes, approach each other through the mutual attraction of their like currents, and merge, through magnetic reconnection, into a single plasma torus, with substantial plasma heating. 2D resistive MHD and Hall MHD simulations of this process are reported, and new results for the temperature distribution of ions and electrons are presented. A model of the based on relaxation theory is also described, which is now extended to tight aspect ratio geometry. This model allows prediction of the final merged state and the heating. The implications of the relaxation model for heating of the solar corona are also discussed, and a model of the merger of two or more twisted coronal flux ropes is presented, allowing for different senses of twist

Bioenergetic relevance of hydrogen sulfide and the interplay between gasotransmitters at human cystathionine β-synthase

Merely considered as a toxic gas in the past, hydrogen sulfide (H2S) is currently viewed as the third ‘gasotransmitter’ in addition to nitric oxide (NO) and carbon monoxide (CO), playing a key signalling role in human (patho)physiology. H2S can either act as a substrate or, similarly to CO and NO, an inhibitor of mitochondrial respiration, in the latter case by targeting cytochrome c oxidase (CcOX). The impact of H2S on mitochondrial energy metabolism crucially depends on the bioavailability of this gaseous molecule and its interplay with the other two gasotransmitters. The H2S-producing human enzyme cystathionine β-synthase (CBS), sustaining cellular bioenergetics in colorectal cancer cells, plays a role in the interplay between gasotransmitters. The enzyme was indeed recently shown to be negatively modulated by physiological concentrations of CO and NO, particularly in the presence of its allosteric activator S-adenosyl-L-methionine (AdoMet). These newly discovered regulatory mechanisms are herein reviewed. This article is part of a Special Issue entitled ‘EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2–6, 2016’, edited by Prof. Paolo Bernardi

Catchment features controlling nitrogen dynamics in running waters above the tree line (central Italian Alps)

The study of nitrogen cycling in mountain areas has a long tradition, as it was applied to better understand and describe ecosystem functioning, as well as to quantify long-distance effects of human activities on remote environments. Nonetheless, very few studies, especially in Europe, have considered catchment features controlling nitrogen dynamics above the tree line with focus on running waters. In this study, relationships between some water chemistry descriptors – including nitrogen species and dissolved organic carbon (DOC) – and catchment characteristics were evaluated for a range of sites located above the tree line (1950–2650 m a.s.l.) at Val Masino, in the central Italian Alps. Land cover categories as well as elevation and slope were assessed at each site. Water samples were collected during the 2007 and 2008 snow free periods, with a nearly monthly frequency. In contrast to dissolved organic nitrogen, nitrate concentrations in running waters showed a spatial pattern strictly connected to the fractional extension of tundra and talus in each basin. Exponential models significantly described the relationships between maximum NO3 and the fraction of vegetated soil cover (negative relation) and talus (positive relation), explaining almost 90% of nitrate variation in running waters. Similarly to nitrate but with an opposite behavior, DOC was positively correlated with vegetated soil cover and negatively correlated with talus. Therefore, land cover can be considered one of the most important factors affecting water quality in high-elevation catchments with contrasting effects on N and C pools

IL-12-dependent innate immunity arrests endothelial cells in G0-G1 phase by a p21(Cip1/Waf1)-mediated mechanism.

Innate immunity may activate paracrine circuits able to entail vascular system in the onset and progression of several chronic degenerative diseases. In particular, interleukin (IL)-12 triggers a genetic program in lymphomononuclear cells characterized by the production of interferon-γ and specific chemokines resulting in an angiostatic activity. The aim of this study is to identify molecules involved in the regulation of cell cycle in endothelial cells co-cultured with IL-12-stimulated lymphomonuclear cells. By using a transwell mediated co-culture system we demonstrated that IL-12-stimulated lymphomonuclear cells induce an arrest of endothelial cells cycle in G1, which is mainly mediated by the up-regulation of p21(Cip1/Waf1), an inhibitor of cyclin kinases. This effect requires the activation of STAT1, PKCδ and p38 MAPK, while p53 is ineffective. In accordance, siRNA-dependent silencing of these molecules in endothelial cells inhibited the increase of p21(Cip1/Waf1) and the modification in cell cycle promoted by IL-12-stimulated lymphomonuclear cells. These results indicate that the angiostatic action of IL-12-stimulated lymphomononuclear cells may lie in the capability to arrest endothelial cells in G1 phase through a mechanisms mainly based on the specific up-regulation of p21(Cip1/Waf1) induced by the combined activity of STAT1, PKCδ and p38 MAPK

Type I collagen limits VEGFR-2 signaling by a SHP2 protein-tyrosine phosphatase-dependent mechanism 1.

During angiogenesis, a combined action between newly secreted extracellular matrix proteins and the repertoire of integrins expressed by endothelial cells contributes in the regulation of their biological functions. Extracellular matrix-engaged integrins influence tyrosine kinase receptors, thus promoting a regulatory cross-talk between adhesive and soluble stimuli. For instance, vitronectin has been reported to positively regulate VEGFR-2. Here, we show that collagen I downregulates VEGF-A-mediated VEGFR-2 activation. This activity requires the tyrosine phosphatase SHP2, which is recruited to the activated VEGFR-2 when cells are plated on collagen I, but not on vitronectin. Constitutive expression of SHP2(C459S) mutant inhibits the negative role of collagen I on VEGFR-2 phosphorylation. VEGFR-2 undergoes internalisation, which is associated with dynamin II phosphorylation. Expression of SHP2(C459S) impairs receptor internalisation suggesting that SHP2-dependent dephosphorylation regulates this process. These findings demonstrate that collagen I in provisional extracellular matrix surrounding nascent capillaries triggers a signaling pathway that negatively regulates angiogenesis