SCHEDULING IN THE SERVICE INDUSTRIES:AN OVERVIEW

Scheduling plays an important role in many different service industries.In this paper we provide an overview of some of the more important scheduling problems that appear in the various service industries.We focus on the formulations of such problems as well as on the techniques used for solving those problems.We consider five areas of scheduling in service industries,namely(i) project scheduling,(ii) workforce scheduling,(iii) timetabling,reservations,and appointments,(iv)transportation scheduling,and(v) scheduling in entertainment.The first two areas are fairly general and have applications in many different service industries.The third,fourth and fifth areas are more related to some very specific service industries,namely the hospitality and health care industries,the transportation industries(of passengers as well as of cargo),and the entertainment industries.In our conclusion section we discuss the similarities and the differences between the problem formulations and solution techniques used in the various different industries and we also discuss the design of the decision support systems that have been developed for scheduling in the service industries.     

Different functional outcomes of intercellular membrane transfers to monocytes and T cells

Trogocytosis is the uptake of membranes from one cell by another. Trogocytosis has been demonstrated for monocytes, B cells, T cells, and NK cells. The acquisition of the tolerogenic molecule HLA-G by T cells and NK cells makes them behave as regulatory cells. We investigated here whether HLA-G, which is expressed by tumor cells in vivo, could be acquired by monocytes and if this transfer could have functional consequences. We demonstrate that resting, and even more so, activated monocytes efficiently acquire membrane-bound HLA-G from HLA-G tumor cells by trogocytosis. However, we demonstrate that HLA-G quickly disappears from the surface of the monocytes in contrast to the HLA-G acquired by T cells. Consequently, HLA-G^acq+ monocytes do not reliably inhibit the on-going proliferation of autologous activated T cells and do not inhibit their cytokine production. Thus, we show that the acquirer cell may control the functional outcome of trogocytosis.     

Caveolin regulation of neuronal intracellular signaling

Caveolin proteins physically interact with and compartmentalize membrane-localized signaling proteins to facilitate high-fidelity intracellular signaling. Though primarily studied outside the nervous system, recent investigations have revealed that caveolin proteins are key modulators of a variety of neuronal intracellular signaling pathways. Through both protein aggregation and segregation, caveolin proteins can exert positive and negative influences on intracellular signaling. This review will detail recent findings regarding caveolin function in the brain.     

Variations in carbon isotopic composition in the subcontinental lithospheric mantle beneath the Yangtze and North China Cratons: Evidence from in-situ analysis of diamonds using SIMS

The components and evolution of subcontinental lithospheric mantle beneath the North China Craton and the Yangtze Craton is a current topic in the geological study of China and the carbon isotopic composition of diamond is one of the most direct probes into cratonic lithospheric mantle processes.In this paper,in-situ SIMS(Secondary Ion Mass Spectrometry) techniques were used to analyze the carbon isotope compositions at different internal growth zones of diamonds from Shandong and Liaoning in the North China Craton and Hunan in the Yangtze Craton.It was found that the carbon isotopic range of diamonds from the North China Craton are rather distinct from those of the Yangtze Craton;the former has a range of 6.0‰ to 2.0‰(relative to VPDB) with an average value of 3.0‰ in their core areas,which is consistent with global peridotitic diamonds;the diamonds from the Yangtze Craton,however,have a carbon isotopic range from 8.6‰ to 3.0‰ with an average value of 7.4‰ in their core areas,being more consistent with global eclogitic diamonds.The variations of carbon isotope ratios between different internal growth zones in individual diamonds were different in the three diamond localities studied.There was a clear correlation between changes in carbon isotopic composition and phases of diamond dissolution and new growth,while no correlation was observed between δ13C and internal inclusions.The variations suggest that the carbon isotopic compositions of mantle fluids were changing during the process of diamond crystallization,and that the heterogeneity of the carbon isotopic composition in mantle carbon reservoirs was a more important factor than carbon isotope fractionation in controlling the carbon isotopic compositions and their variation in diamonds.In addition,the preliminary results of in-situ nitrogen analyses demonstrated that the variation of carbon isotopic compositions between the core and outer growth zones does not correlate with nitrogen abundances,implying either that diamonds crystallized in an open environment or that the carbon isotopic composition and nitrogen contents in mantle fluids were controlled by other,not yet understood factors.The experimental results provide hints that the isotopic composition of carbon and its original sources were different in metasomatic fluids controlling diamond formation in the mantle beneath the North China Craton and the Yangtze Craton.     

Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen

Abnormalities of platelet functions have been linked to reelin-impaired neuronal disorders. However, little attention has been given to understanding the interplay between reelin and platelet. In this study, reelin was found to present in the human platelets and megakaryocyte-like leukemic cells. Reelin-binding assays revealed that extracellular reelin can interact with platelets through the receptor belonging to the low density lipoprotein receptor gene family. The reelin-to-platelet interactions enhance platelet spreading on fibrinogen concomitant with the augmentation of lamellipodia formation and F-actin bundling. In contrast, reelin has no effect on integrin αIIbβ3 activation and agonist-induced platelet aggregation. Molecular analysis revealed that the up-regulation of Rac1 activity and the inhibition of protein kinase C δ-Thr505 phosphorylation are important for reelin-mediated enhancement of platelet spreading on fibrinogen. These findings demonstrate for the first time that reelin is present in platelets and the reelin-to-platelet interactions play a novel role in platelet signaling and functions.     

Conserved noncoding sequences are selectively constrained and not mutation cold spots

Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals, suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new (derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation.     

Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2

We have identified a recurrent de novo pericentromeric deletion in 16p11.2-p12.2 in four individuals with developmental disabilities by microarray-based comparative genomic hybridization analysis. The identification of common clinical features in these four individuals along with the characterization of complex segmental duplications flanking the deletion regions suggests that nonallelic homologous recombination mediated these rearrangements and that deletions in 16p11.2-p12.2 constitute a previously undescribed syndrome.     

LOX-1 in atherosclerosis: biological functions and pharmacological modifiers

Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis.     

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.