Experimental Validation of Travel Time Models for Shuttle-based Automated Storage and Retrieval System

In this paper, we aim to validate travel time models for single and dual command cycle displacements of lifts and shuttles in a shuttle-based automated storage and retrieval system (SBS/RS) by using experimental computer simulation. The models under consideration take into account acceleration and deceleration delays. We use ARENA 12 software for the simulation modeling. By simulation, we emulate the real functioning of the system. Therefore, we assume that the results from the ARENA simulation are equivalent to the onsite experimentation. Simulation results are very close to those obtained by analytical travel time models. This shows the high precision of these models to predict operations of SBS/RS.These models can be used at design or operation phases to calculate throughput of the system, to compare between different topologies of SBS/RS or with other types of AS/RS to help decision makers to choose among different alternatives of automated storage systems

Method for evaluating the throughput performance of shuttle based storage and retrieval systems

U ovom radu prezentira se metoda proračuna protočne performanse skladišnih sustava sa shuttle-ovima/vozilima (eng. SBS/RS). SBS/RS zastupaju novu tehnologiju automatiziranih skladišnih sustava. S obzirom na važnost ispravnog oblikovanja (projektiranja) SBS/RS sustava "od prve" zbog relativne nefleksibilnosti fizičke izvedbe, prezentira se predložena metoda proračuna protočne performanse takvih sustava. Performansa sustava razmatra se kao protočni kapacitet SBS/RS kao cjeline.In this paper a method for throughput performance calculation of shuttle based storage and retrieval systems (SBS/RS) is presented. SBS/RS represent a new technology in automated storage and retrieval systems. Since it is important to design SBS/RS right the first time due to the relative inflexibility of the physical layout, we provide a proposed method for the throughput performance calculation of these systems. The performance of the system is considered as a throughput capacity of the SBS/RS as a whole

Multi-objective optimisation model of shuttle-based storage and retrieval system

This paper presents a multi-objective optimisation solution procedure for the design of the Shuttle-Based Storage and Retrieval System (SBS/RS). An efficient SBS/RS design should take into account multi-objectives for optimization. In this study, we considered three objective functions in the design concept which are the minimization of average cycle time of transactions (average throughput time), amount of energy (electricity) consumption and total investment cost. By also considering the amount of energy consumption as an objective function for minimization, we aimed to contribute to an environmentally friendly design concept. During the optimization procedure, we considered seven design variables as number of aisles, number of tiers, number of columns, velocities of shuttle carriers, acceleration/deceleration of shuttle carriers, velocity of the elevators lifting tables and acceleration/deceleration of the elevators lifting tables. Due to the non-linear property of the objective function, we utilized the Non-Dominated Sorting Genetic Algorithm II (NSGA II) genetic algorithm for facilitating the solution. Lastly, we searched Pareto optimal solutions to find out the optimum results. We believe that this study provides a useful and a flexible tool for warehouse planners and designers, while choosing a particular type of SBS/RS at the early stage of the warehouse design. First published online: 12 May 201

Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72178/1/j.1751-553X.2007.01016.x.pd

The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells

Regulatory T cells (Tregs) have a central role in maintaining immune homoeostasis through various mechanisms. Although the Forkhead transcription factor Foxp3 defines the Treg cell lineage and functions, the molecular mechanisms of Foxp3 induction and maintenance remain elusive. Here we show that Foxp3 is one of the direct targets of Nr4a2. Nr4a2 binds to regulatory regions of Foxp3, where it mediates permissive histone modifications. Ectopic expression of Nr4a2 imparts Treg-like suppressive activity to naïve CD4+ T cells by inducing Foxp3 and by repressing cytokine production, including interferon-γ and interleukin-2. Deletion of Nr4a2 in T cells attenuates induction of Tregs and causes aberrant induction of Th1, leading to the exacerbation of colitis. Nr4a2-deficeint Tregs are prone to lose Foxp3 expression and have attenuated suppressive ability both in vitro and in vivo. Thus, Nr4a2 has the ability to maintain T-cell homoeostasis by regulating induction, maintenance and suppressor functions of Tregs, and by repression of aberrant Th1 induction

GITR signaling potentiates airway hyperresponsiveness by enhancing Th2 cell activity in a mouse model of asthma

<p>Abstract</p> <p>Background</p> <p>Allergic asthma is characterized by airway hyperresponsiveness (AHR) and allergic inflammation of the airways, driven by allergen-specific Th2 cells. The asthma phenotypes and especially AHR are sensitive to the presence and activity of regulatory T (Treg) cells in the lung. Glucocorticoid-induced tumor necrosis factor receptor (GITR) is known to have a co-stimulatory function on effector CD4⁺T cells, rendering these cells insensitive to Treg suppression. However, the effects of GITR signaling on polarized Th1 and Th2 cell effector functions are not well-established. We sought to evaluate the effect of GITR signaling on fully differentiated Th1 and Th2 cells and to determine the effects of GITR activation at the time of allergen provocation on AHR and airway inflammation in a Th2-driven mouse model of asthma.</p> <p>Methods</p> <p>CD4⁺CD25^-cells were polarized <it>in vitro </it>into Th1 and Th2 effector cells, and re-stimulated in the presence of GITR agonistic antibodies to assess the effect on IFNγ and IL-4 production. To evaluate the effects of GITR stimulation on AHR and allergic inflammation in a mouse asthma model, BALB/c mice were sensitized to OVA followed by airway challenges in the presence or absence of GITR agonist antibodies.</p> <p>Results</p> <p>GITR engagement potentiated cytokine release from CD3/CD28-stimulated Th2 but not Th1 cells <it>in vitro</it>. In the mouse asthma model, GITR triggering at the time of challenge induced enhanced airway hyperresponsiveness, serum IgE and <it>ex vivo </it>Th2 cytokine release, but did not increase BAL eosinophilia.</p> <p>Conclusion</p> <p>GITR exerts a differential effect on cytokine release of fully differentiated Th1 and Th2 cells <it>in vitro</it>, potentiating Th2 but not Th1 cytokine production. This effect on Th2 effector functions was also observed <it>in vivo </it>in our mouse model of asthma, resulting in enhanced AHR, serum IgE responses and Th2 cytokine production. This is the first report showing the effects of GITR activation on cytokine production by polarized primary Th1 and Th2 populations and the relevance of this pathway for AHR in mouse models for asthma. Our data provides crucial information on the mode of action of the GITR signaling, a pathway which is currently being considered for therapeutic intervention.</p

Integrating the data envelopment analysis and the balanced scorecard approaches for enhanced performance assessment

This article presents the development of a conceptual framework which aims to assess Decision Making Units (DMUs)from multiple perspectives. The proposed conceptual framework combines the Balanced Scorecard(BSC)method with the non-parametric technique known as Data Envelopment Analysis (DEA) by using various interconnected models which try to encapsulate four perspectives of performance (financial, customers, internal processes,learning and growth). The practical relevance of the conceptual model has been tested by using it to assess the performance of DMUs in a multinational company which operates in two business areas.Various models were developed with the collaboration of the directors of the company in order to conceive an appropriate and consensual framework, which may provide useful information for the company.The application of the conceptual framework provides structured information regarding the performance of each DMU(from multiple perspectives)and ways to improve it.By integrating the BSC and the DEA approaches this research helps to identify where there is room for improving organisational performance and points out opportunities for reciprocal learning between DMUs.In doing so,this article provides a set of recommendations relating to the successful application of DEA and its integration with the BSC,in order to promote a continuous learning process and to bring about improvements in performance

Murine B Cell Development and Antibody Responses to Model Antigens Are Not Impaired in the Absence of the TNF Receptor GITR

The Glucocorticoid-Induced Tumor necrosis factor Receptor GITR, a member of the tumor necrosis factor receptor superfamily, has been shown to be important in modulating immune responses in the context of T cell immunity. B lymphocytes also express GITR, but a role of GITR in humoral immunity has not been fully explored. To address this question, we performed studies to determine the kinetics of GITR expression on naïve and stimulated B cells and the capacity of B cells to develop and mount antibody responses in GITR−/− mice. Results of our studies indicate that all mature B cells express GITR on the cell surface, albeit at different levels. Expression of GITR on naïve mature B cells is upregulated by BCR signaling, but is counteracted by helper T cell-related factors and other inflammatory signals in vitro. In line with these findings, expression of GITR on germinal center and memory B cells is lower than that on naïve B cells. However, the expression of GITR is strongly upregulated in plasma cells. Despite these differences in GITR expression, the absence of GITR has no effect on T cell-dependent and T cell-independent antibody responses to model antigens in GITR−/− mice, or on B cell activation and proliferation in vitro. GITR deficiency manifests only with a slight reduction of mature B cell numbers and increased turnover of naïve B cells, suggesting that GITR slightly contributes to mature B cell homeostasis. Overall, our data indicate that GITR does not play a significant role in B cell development and antibody responses to T-dependent and independent model antigens within the context of a GITR-deficient genetic background

Antiproliferative effects of Tubi-bee propolis in glioblastoma cell lines

Propolis is a resin formed by a complex chemical composition of substances that bees collect from plants. Since ancient times, propolis has been used in folk medicine, due to its biological properties, that include antimicrobial, anti-inflammatory, antitumoral and immunomodulatory activities. Glioblastoma is the most common human brain tumor. Despite the improvements in GBM standard treatment, patients’ prognosis is still very poor. The aim of this work was to evaluate in vitro the Tubi-bee propolis effects on human glioblastoma (U251 and U343) and fibroblast (MRC-5) cell lines. Proliferation, clonogenic capacity and apoptosis were analyzed after treatment with 1 mg/mL and 2 mg/mL propolis concentrations for different time periods. Additionally, glioblastoma cell lines were submitted to treatment with propolis combined with temozolomide (TMZ). Data showed an antiproliferative effect of tubi-bee propolis against glioblastoma and fibroblast cell lines. Combination of propolis with TMZ had a synergic anti-proliferative effect. Moreover, propolis caused decrease in colony formation in glioblastoma cell lines. Propolis treatment had no effects on apoptosis, demonstrating a cytostatic action. Further investigations are needed to elucidate the molecular mechanism of the antitumor effect of propolis, and the study of its individual components may reveal specific molecules with antiproliferative capacity