Load-based generic polca: performance assessement using simulation

POLCA (i.e. Paired-cell Overlapping Loops of Cards with Authorization) is a card-based decision support system for production control, developed to support the adoption of Quick Response Manufacturing. Two variants of POLCA have been proposed in the literature to improve POLCA performance: Load Based POLCA and Generic POLCA. In this paper, we combine these two variants into a single production control system and analyse its performance for different backlog-sequencing rules. The results of a simulation study carried out for a make-to-order flow shop, support the strategy of combining these two POLCA variants and show that capacity-slack backlog sequencing based on corrected aggregate load have the potential for improving performance.info:eu-repo/semantics/publishedVersio

Scour protection design in highly morphodynamic environments

Offshore wind parks are often developed in areas with a highly morphodynamic seabed. In order to keep the pile fixation level within acceptable limits for pile design, sophisticated scour mitigation strategies are required. This paper discusses the scour protection strategy for the Nordergründe Offshore Wind Farm, where 10m seabed level drops are predicted at some monopile locations. Physical model tests were performed to validate the scour protection design, focussing on correct falling apron behaviour and the stability of the loose rock scour protection. The outcome of the tests showed good correlation with a modified relative mobility parameter. Using this parameter, the scour protection was optimised for the individual pile locations

Evaluation of the Antiviral Response to Zanamivir Administered Intravenously for Treatment of Critically Ill Patients With Pandemic Influenza A (H1N1) Infection

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4–11 days) compared with 14 days (range, 6–21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated

CD4+ and CD8+ T Cells Can Act Separately in Tumour Rejection after Immunization with Murine Pneumotropic Virus Chimeric Her2/neu Virus-Like Particles

BACKGROUND: Immunization with murine pneumotropic virus virus-like particles carrying Her2/neu (Her2MPtVLPs) prevents tumour outgrowth in mice when given prophylactically, and therapeutically if combined with the adjuvant CpG. We investigated which components of the immune system are involved in tumour rejection, and whether long-term immunological memory can be obtained. METHODOLOGY AND RESULTS: During the effector phase in BALB/c mice, only depletion of CD4+ and CD8+ in combination, with or without NK cells, completely abrogated tumour protection. Depletion of single CD4+, CD8+ or NK cell populations only had minor effects. During the immunization/induction phase, combined depletion of CD4+ and CD8+ cells abolished protection, while depletion of each individual subset had no or negligible effect. When tumour rejection was studied in knock-out mice with a C57Bl/6 background, protection was lost in CD4-/-CD8-/- and CD4-/-, but not in CD8-/- mice. In contrast, when normal C57Bl/6 mice were depleted of different cell types, protection was lost irrespective of whether only CD4+, only CD8+, or CD4+ and CD8+ cells in combination were eradicated. No anti-Her2/neu antibodies were detected but a Her2/neu-specific IFNgamma response was seen. Studies of long-term memory showed that BALB/c mice could be protected against tumour development when immunized together with CpG as long as ten weeks before challenge. CONCLUSION: Her2MPtVLP immunization is efficient in stimulating several compartments of the immune system, and induces an efficient immune response including long-term memory. In addition, when depleting mice of isolated cellular compartments, tumour protection is not as efficiently abolished as when depleting several immune compartments together

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe

Ground-gamma band mixing and odd-even staggering in heavy deformed nuclei

It is proposed that the odd-even staggering (OES) in the $\gamma$- bands of heavy deformed nuclei can be reasonably characterized by a discrete approximation of the fourth derivative of the odd-even energy difference as a function of angular momentum $L$. This quantity exhibits a well developed staggering pattern (zigzagging behavior with alternating signs) in rare earth nuclei and actinides with long $\gamma$- bands ($L\geq 10$). It is shown that the OES can be interpreted reasonably as the result of the interaction of the $\gamma$ band with the ground band in the framework of a Vector Boson Model with SU(3) dynamical symmetry. The model energy expression reproduces successfully the staggering pattern in all considered nuclei up to $L=12-13$. The general behavior of the OES effect in rotational regions is studied in terms of the ground--$\gamma$ band-mixing interaction, showing that strong OES effect occurs in regions with strong ground--$\gamma$ band-mixing interaction. The approach used allows a detailed comparison of the OES in $\gamma$ bands with the other kinds of staggering effects in nuclei and diatomic molecules.Comment: 25 pages, 11 postscript figure

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

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