15 research outputs found

    CVRP with sequence based pallet loading and axle weight restrictions with and without dense packing

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    Abstract This paper presents an Iterated Local Search (ILS) for the CVRP with sequence based pallet loading and axle weight restrictions with and without dense packing. The problem deals with the distribution of pallets to different locations while taking into account that items may not be shifted during the trip and that axle weight limits need to be respected. The structure of the metaheuristic as well as preliminary results will be discussed

    Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model

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    Background: Exposure to diisocyanates is an important cause of occupational asthma (OA) in the industrialized world. Since OA occurs after long-term exposure to diisocyanates, we developed a chronic mouse model of chemical-induced asthma where toluene diisocyanate (TDI) was administered at two different exposure sites. Objectives: Evaluating the effect of long-term respiratory isocyanate exposure - with or without prior dermal exposure- on sensitization, inflammatory responses and airway hyperreactivity (AHR). Methods: On days 1 and 8, BALB/c mice were dermally treated (20 mu 1/ear) with 0.5% 2,4-toluene diisocyanate TDI or the vehicle acetone olive oil (AOO) (3:2). Starting from day 15, mice received intranasal instillations with 0.1% TDI of vehicle five times in a week, for five successive weeks. One day after the last instillation airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and structural lung changes. Immune-related parameters were assessed in the lungs (BAL and tissue), blood, cervical-and auricular lymph nodes. Results: Mice repeatedly intranasally exposed to TDI showed systemic sensitization and a mixed Th1/Th2 type immune response, without the presence of AHR. However, when mice are first dermally sensitized with TDI, followed by repeated intranasal TDI challenges, this results in a pronounced Th2 response and AHR. Conclusion: Dermal exposure to TDI determines airway hyperreactivity after repeated airway exposure to TDI

    Designing a State-of-the-Art Information System for Air Cargo Palletizing

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    DESRIST 2020, Kristiansand, Norway, December 2–4, 2020. Palletizing in air cargo faces a large number of constraints, e.g. aviation safety and cargo handling regulations. In addition, operational, economical, and ecological goals further need to be considered. The challenge to find practicable if not optimal palletizing solutions is known as the Pallet Loading Problem (PLP) or Container Loading Problem (CLP). It defines a np-hard and highly complex problem space. In air cargo operations, there is hardly any digital support to optimize the palletizing process. As a result, desired objectives are often only met by chance, e.g. the optimal utilization of the possible loading weight, the maximum use of the available loading space, or both. The goal of this research is to report on the design and learnings from a state-of-the-art information system we built to support the manual palletizing process by considering substantially more constraints than any other system we know of. The artifact generates via heuristics optimized and practicable palletizing solutions and supports the human palletizer prior to and during the physical assembly by visualizing, monitoring and validating the generated palletizing solutions

    IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

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    <div><p>Background</p><p>While the importance of the Th2 cytokine IL-13 as a central mediator of airway hyperreactivity (AHR) has been described in allergic protein-induced asthma, this has never been investigated in chemical-induced asthma.</p><p>Objective</p><p>We examined the importance of IL-13 in a mouse model of chemical-induced AHR, using toluene-2,4-diisocyanate (TDI).</p><p>Methods</p><p>In a first set-up, wild type (WT) and <i>IL-13</i> knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with 1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control antibody prior to the intranasal challenge.</p><p>Results</p><p>TDI-sensitized and TDI-challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and TDI-challenged <i>IL-13</i> KO mice, which also showed lower levels of total serum IgE. TDI-sensitized and TDI-challenged <i>IL-13</i> KO mice had lower numbers of T-cells in the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no AHR, in contrast to those receiving control antibody, despite increased levels of IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of serum IL-13, but did not induce changes in T- and B-cell numbers, and in the cytokine production profile.</p><p>Conclusion and clinical relevance</p><p>We conclude that IL-13 plays a critical role in the effector phase of chemical-induced, immune-mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial effect in patients with this asthma phenotype.</p></div

    Involvement of innate lymphoid cells and dendritic cells in a mouse model of chemical-induced asthma

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    Purpose: Exposure to low concentrations of toluene diisocyanate (TDI) leads to immunemediated chemical-induced asthma. The role of the adaptive immune system has already been thoroughly investigated; nevertheless, the involvement of innate immune cells in the pathophysiology of chemical-induced asthma is still unresolved. The aim of the study is to investigate the role of innate lymphoid cells (ILCs) and dendritic cells (DCs) in a mouse model for chemical-induced asthma. Methods: On days 1 and 8, BALB/c mice were dermally treated (20 mu L/ear) with 0.5% TDI or the vehicle acetone olive oil (AOO; 2:3). On days 15, 17, 19, 22 and 24, the mice received an oropharyngeal challenge with 0.01% TDI or AOO (1:4). One day after the last challenge, airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and immune-related parameters, including the cytokine pattern in bronchoalveolar lavage fluid, lymphocyte subpopulations of the lymph nodes and their ex vivo cytokine production profile, blood immunoglobulins and DC and ILC subpopulations in the lungs. Results: Both DC and ILC2 were recruited to the lungs after multiple airway exposures to TDI, regardless of the prior dermal sensitization. However, prior dermal sensitization with TDI alone results in AHR and predominant eosinophilic airway inflammation, accompanied by a typical type 2 helper T (Th2) cytokine profile. Conclusions: TDI-induced asthma is mediated by a predominant type 2 immune response, with the involvement of adaptive Th2 cells. However, from our study we suggest that the innate ILC2 cells are important additional players in the development of TDI-induced asthma

    Airway and immune responses in <i>IL-13</i> KO mice.

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    <p>(A) Dose-response curves of R<sub>n</sub> to methacholine (0–20 mg/mL). (B) Individual values and group means of the corresponding area under the curve (AUC) of airway hyperreactivity. (C) Total serum immunoglobulin E (IgE) and (D) IL-13 levels. (E) Lymphocyte subpopulations from auricular lymph nodes, stained with anti-CD3<sup>+</sup>, anti-CD3<sup>+</sup>CD4<sup>+</sup>, anti-CD3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup> and anti-CD3<sup>+</sup>CD8<sup>+</sup> or with anti-CD19<sup>+</sup>. Associated cytokine release of (F) IL-13, (G) IFN-γ and (H) IL-10. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 and *** p < 0.001 compared to own corresponding control group (WT AOO/AOO or <i>IL-13</i> KO AOO/AOO group). <sup>#</sup> p < 0.05, <sup>##</sup> p < 0.01 and <sup>###</sup> p < 0.001 compared to WT TDI/TDI group. N.D., non-detectable levels. n = 5–8 per group.</p

    Airway and immune responses in anti-IL-13 treated WT mice.

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    <p>(A) Dose-response curves of R<sub>n</sub> to methacholine (0–20 mg/mL). (B) Individual values and group means of corresponding area under the curve (AUC) of airway hyperreactivity. (C) Total serum immunoglobulin E (IgE) and (D) IL-13 levels. (E) Lymphocyte subpopulations from auricular lymph nodes, stained with anti-CD3<sup>+</sup>, anti-CD3<sup>+</sup>CD4<sup>+</sup>, anti-CD3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup> and anti-CD3<sup>+</sup>CD8<sup>+</sup> or with anti-CD19<sup>+</sup>. Associated cytokine release of (F) IL-13, (G) IFN-γ and (H) IL-10. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 and *** p < 0.001 compared to own corresponding control group (AOO/gp120/AOO or AOO/anti-IL-13/AOO), <sup>#</sup> p < 0.05, <sup>##</sup> p < 0.01 and <sup>###</sup> p < 0.001 compared to WT TDI/gp120/TDI group. n = 8 per group.</p

    The use of an in vitro technique to predict the absorption of dietary radiocaesium by sheep

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    The validity of an in vitro extraction technique to predict the availability for absorption of radiocaesium in the sheep gut has been assessed. The technique (a 2-h extraction with caesium chloride) was found to be valid for sources with a low availability for transfer across the gut, but inappropriate for ionic radiocaesium or radiocaesium incorporated internally within herbage. For such radiocaesium sources, which have a high in vitro availability, no correlation was found between in vitro extraction and true absorption measurements. A true absorption value of 0.80 is recommended for these sources, although values for individual sheep in the range 0.60 to 1.00 should be expected
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