37,226 research outputs found

    The expression and signalling patterns of CD180 toll like receptor in Chronic Lymphocytic Leukaemia (CLL)

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    Chronic lymphocytic leukaemia (CLL) is characterised by a progressive accumulation of mature CD5+CD20+CD23+ lymphocytes. Despite the remarkable progress in our understanding of the immunobiology of CLL, the aetiology of the disease remains unknown. The consensus is that CLL cells are driven by (auto)antigen(s) through the B cell receptor (BCR) and are regulated by a variety of signals received from the microenvironment, including toll-like receptors (TLR).Our group has previously shown that engagement of the CD180 orphan TLR expressed by approximately 60% of CLL cells, can re-wire the sIgM-mediated signalling from a pro-survival pathway, involving phosphatidylinositol-4,5-bisphosphate3-kinase (PI3K) and protein kinase B (AKT) to the potentially pro-apoptotic pathway through mitogen-activated protein kinase (p38MAPK). However, little is known about the function of the other BCR - sIgD in CLL and its possible interaction with CD180. Here we studied intracellular signalling and apoptosis of CLL cells following sole or sequential ligation of CD180 and sIgD. Our data indicated that following sequential ligation of CD180 and sIgD, CLL samples demonstrated enhanced p38MAPK phosphorylation leading to increased apoptosis of CLL cells indicating synergistic relationship between CD180 and sIgD. To better understand the prognostic importance of CD180 expression we sought to determine whether CD180 and other prognostic markers such as CD38 and ZAP70 displayed any correlation with the known cytogenetic aberrations:TP53 and DLEU1. Our results suggested that CLL cells with DLEU1 deletion are characterised by the negative expression of both, CD180 and CD38, and this might have a significance for CLL prognosis. To explain this correlation, we hypothesised that interaction of CLL cells with their microenvironment through TLRs leads to the expansion of leukaemic clones, in vivo, in lymph nodes. Our results indicated that CD180 is heterogeneously expressed in the paraffin tissue sections of the lymph nodes of CLL patients and its expression positively correlates with the expression of Ki-67. Our data demonstrated, that although CD180 expression and signaling might have negative prognostic importance in CLL due to the enhanced proliferation of leukaemic cells, its interaction with sIgD would re-direct leukaemic cells towards apoptosis thus opening new opportunities for the disease immunotherapy

    Models and Algorithms for Inbound and Outbound Truck to Door Scheduling

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    Cross-docking is a logistic strategy that facilitates rapid movement of consolidated products between suppliers and retailers within a supply chain. It is also a warehousing strategy that aims at reducing or eliminating storage and order picking, two of which are known to be major costly operations of any typical warehouse. This strategy has been used in the retailing, manufacturing, and automotive industries. In a cross-dock, goods are unloaded from incoming trucks, consolidated according to their destinations, and then, loaded into outgoing trucks with little or no storage in between. In this thesis, we address an integrated cross-dock door assignment and truck scheduling problem in which the assignment and sequencing of incoming trucks to strip doors and outgoing trucks to stack doors is optimized to minimize the total time to process all trucks. We present a mixed integer programming formulation to model this problem and some valid inequalities to strengthen the formulation. We also present two metaheuristics to obtain high quality solutions in reasonable CPU times. These algorithms use a mix of composite dispatching rules, constructive heuristics, local search heuristics which are embedded into a greedy randomized adaptive search procedure (GRASP) and an iterated local search (ILS). Results of computational experiments are presented to assess the performance of the proposed algorithms, in comparison with a general purpose solver

    Blow up and Blur constructions in Algebraic Logic

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    The idea in the title is to blow up a finite structure, replacing each 'colour or atom' by infinitely many, using blurs to represent the resulting term algebra, but the blurs are not enough to blur the structure of the finite structure in the complex algebra. Then, the latter cannot be representable due to a {finite- infinite} contradiction. This structure can be a finite clique in a graph or a finite relation algebra or a finite cylindric algebra. This theme gives examples of weakly representable atom structures that are not strongly representable. Many constructions existing in the literature are placed in a rigorous way in such a framework, properly defined. This is the essence too of construction of Monk like-algebras, one constructs graphs with finite colouring (finitely many blurs), converging to one with infinitely many, so that the original algebra is also blurred at the complex algebra level, and the term algebra is completey representable, yielding a representation of its completion the complex algebra. A reverse of this process exists in the literature, it builds algebras with infinite blurs converging to one with finite blurs. This idea due to Hirsch and Hodkinson, uses probabilistic methods of Erdos to construct a sequence of graphs with infinite chromatic number one that is 2 colourable. This construction, which works for both relation and cylindric algebras, further shows that the class of strongly representable atom structures is not elementary.Comment: arXiv admin note: text overlap with arXiv:1304.114