103 research outputs found

    DaVinc3i: Virtualisation Scenarios For Floricultural Trade Networks

    Get PDF
    The Dutch floricultural industry is generally appreciated for its world leadership; the Netherlands is the trading hub for the European market. There are two trends affecting this position. First, virtualisation of trade and logistics control enabled by technological progress. Second, internationalisation of markets and production reshapes the market in size and distance. To maintain leadership, the Dutch floricultural industry has initiated the Dinalog DaVinc3i project. In this paper we outline the activities we are currently undertaking and some of the outcomes achieved so far. These include 12 commercial scenarios for the future of the industry and specific challenges related to ICT as an enabler of virtualisation in floricultural logistics and trade. Alongside the discussion of these activities and outcomes, we present some thoughts on how to address the challenges based on an (inter)national benchmark carried out as part of the project

    DAVINC3I: moving towards responsive hub network designs

    Get PDF
    The Dutch floricultural sector is generally appreciated for its world leadership; the Netherlands is the flower trading hub for the European market. There are two trends affecting this position. First, virtualisation makes trade flows relatively footloose and flexible. Moreover, it enables the use of better and more information in logistics decision making. Second, internationalisation of markets and production has increased the size of the global market and associated distances. To maintain leadership, the Dutch floricultural sector has initiated the Dinalog DaVinc3i project. In this paper we outline the activities we are currently undertaking and some of the outcomes achieved so far. This includes the effects of orchestration in floriculture logistics and the development of a new logistics network model for floriculture logistics. Subsequently we will provide a brief overview of some of the student projects carried out within the DaVinc3i project: reasons for outsourcing floriculture logistics in export flows, pooling of inventory by florists and collection of flowers in a small network. Finally, aspects of collaboration for product quality are addressed, as well as recommendations for a cooperative business model for a B2C web shop for plants and flowers

    Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.

    Get PDF
    80These guidelines focus on valvular heart disease in adults and adolescents, are oriented towards management, and will not deal with endocarditis and congenital valve diseases in adults and adolescents, since recent guidelines have been produced by the ESC on these topics. Although valvular heart disease is less common in industrialized countries than coronary disease, heart failure, or hypertension, guidelines are needed in this field for several reasons: valvular heart disease is common and often requires intervention; substantial advances have been made in the understanding of its pathophysiology; the patient population has changed with a continuous decline of acute rheumatic fever and an increased incidence of degenerative valvular diseases in industrialized countries. The incidence of endocarditis remains stable and other causes of valve disease are rare. Because of the predominance of degenerative valve disease, the two most frequent valve diseases are now calcific aortic stenosis and mitral regurgitation. Aortic regurgitation and mitral stenosis have become less common. Diagnosis is now dominated by echocardiography, which has become the standard to evaluate valve structure and function. Treatment has not only developed through the continuing progress in prosthetic valve technology, but has also been reoriented by the development of conservative surgical approaches and the introduction of percutaneous interventional techniques.openopenVahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean-Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, ; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke-Baerwolf, ; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo,Vahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, Marco; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke, Baerwolf; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo

    Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis

    Get PDF
    Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.he relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients

    Rheumatoid Arthritis Patients With Circulating Extracellular Vesicles Positive for IgM Rheumatoid Factor Have Higher Disease Activity

    Get PDF
    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Validated laboratory parameters for RA diagnosis are higher blood levels of rheumatoid factor IgM (IgM-RF), anti-citrullinated protein autoantibodies (ACPA), C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR). Clinical parameters used are the number of tender (TJC) and swollen joints (SJC) and the global patient visual analog score (VAS). To determine disease remission in patients a disease activity score (DAS28) can be calculated based on SJC, TJC, VAS, and ESR (or alternatively CRP). However, subtle and better predictive changes to follow treatment responses in individual patients cannot be measured by the above mentioned parameters nor by measuring cytokine levels in blood. As extracellular vesicles (EVs) play a role in intercellular communication and carry a multitude of signals we set out to determine their value as a biomarker for disease activity. EVs were isolated from platelet-free plasma of 41 RA patients and 24 healthy controls (HC) by size exclusion chromatography (SEC). We quantified the particle and protein concentration, using NanoSight particle tracking analysis and micro-BCA, respectively, and observed no differences between RA patients and HC. In plasma of 28 out of 41 RA patients IgM-RF was detectable by ELISA, and in 13 out of these 28 seropositive RA patients (RF+RA) IgM-RF was also detected on their isolated pEVs (IgM-RF+). In seronegative RA patients (RF−RA) we did not find any RF present on pEVs. When comparing disease parameters we found no differences between RF+RA and RF−RA patients, except for increased ESR levels in RF+RA patients. However, RF+RA patients with IgM-RF+ pEVs showed significantly higher levels of CRP and ESR and also VAS and DAS28 were significantly increased compared to RA+ patients without IgM-RF+ pEVs. This study shows for the first time the presence of IgM-RF on pEVs in a proportion of RF+RA patients with a higher disease activity

    Conflict between Genetic and Phenotypic Differentiation: The Evolutionary History of a ‘Lost and Rediscovered’ Shorebird

    Get PDF
    Understanding and resolving conflicts between phenotypic and genetic differentiation is central to evolutionary research. While phenotypically monomorphic species may exhibit deep genetic divergences, some morphologically distinct taxa lack notable genetic differentiation. Here we conduct a molecular investigation of an enigmatic shorebird with a convoluted taxonomic history, the White-faced Plover (Charadrius alexandrinus dealbatus), widely regarded as a subspecies of the Kentish Plover (C. alexandrinus). Described as distinct in 1863, its name was consistently misapplied in subsequent decades until taxonomic clarification ensued in 2008. Using a recently proposed test of species delimitation, we reconfirm the phenotypic distinctness of dealbatus. We then compare three mitochondrial and seven nuclear DNA markers among 278 samples of dealbatus and alexandrinus from across their breeding range and four other closely related plovers. We fail to find any population genetic differentiation between dealbatus and alexandrinus, whereas the other species are deeply diverged at the study loci. Kentish Plovers join a small but growing list of species for which low levels of genetic differentiation are accompanied by the presence of strong phenotypic divergence, suggesting that diagnostic phenotypic characters may be encoded by few genes that are difficult to detect. Alternatively, gene expression differences may be crucial in producing different phenotypes whereas neutral differentiation may be lagging behind

    Tim-3 Negatively Regulates IL-12 Expression by Monocytes in HCV Infection

    Get PDF
    T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a newly identified negative immunomodulator that is up-regulated on dysfunctional T cells during viral infections. The expression and function of Tim-3 on human innate immune responses during HCV infection, however, remains poorly characterized. In this study, we report that Tim-3 is constitutively expressed on human resting CD14+ monocyte/macrophages (M/MØ) and functions as a cap to block IL-12, a key pro-inflammatory cytokine linking innate and adaptive immune responses. Tim-3 expression is significantly reduced and IL-12 expression increased upon stimulation with Toll-like receptor 4 (TLR4) ligand - lipopolysaccharide (LPS) and TLR7/8 ligand - R848. Notably, Tim-3 is over-expressed on un-stimulated as well as TLR-stimulated M/MØ, which is inversely associated with the diminished IL-12 expression in chronically HCV-infected individuals when compared to healthy subjects. Up-regulation of Tim-3 and inhibition of IL-12 are also observed in M/MØ incubated with HCV-expressing hepatocytes, as well as in primary M/MØ or monocytic THP-1 cells incubated with HCV core protein, an effect that mimics the function of complement C1q and is reversible by blocking the HCV core/gC1qR interaction. Importantly, blockade of Tim-3 signaling significantly rescues HCV-mediated inhibition of IL-12, which is primarily expressed by Tim-3 negative M/MØ. Tim-3 blockade reduces HCV core-mediated expression of the negative immunoregulators PD-1 and SOCS-1 and increases STAT-1 phosphorylation. Conversely, blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation. These findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through crosstalk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection

    Кинетика восстановления железа при восстановительной плавке рудоугольных окатышей

    Get PDF
    Исследовано влияние интенсивности теплообмена на кинетику восстановления железа в процессе плавки рудоугольных окатышей. Показано, что с ростом интенсивности теплообмена повышается скорость восстановительных процессов. Вследствие роста коэффициента теплообмена увеличивается глубина восстановленного слоя окатыша, существенно изменяются его структура и химический состав образующейся металлической фазы.Досліджено вплив інтенсивності теплообміну на кінетику відновлення заліза в процесі плавки рудовугільних окатишів. Показано, що при зростанні інтенсивності теплообміну підвищується швидкість відновлювальних процесів. Внаслідок зростання коефіцієнту теплообміну збільшується глибина відновленого шару окатиша, суттєво змінюються його структура та хімічний склад металевої фази, що утворюється.Influence of intensity of heat exchange is investigational on kinetics reduction of iron in the process of melting ore-coal pellets. It is rotined that speed of reduction processes rises with growth of intensity of heat exchange. Because of growth of coefficient of heat exchange the depth of the recovered layer of pellet is increased, his structure and chemical composition of appearing metallic phase changes substantially
    corecore