30 research outputs found

    A branch‐and‐price‐based heuristic for the vehicle routing problem with two‐dimensional loading constraints and time windows

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    AbstractAddressed in this study is a vehicle routing problem with two‐dimensional loading constraints and time windows (2L‐CVRPTW), aiming to minimize the transportation cost while satisfying the two‐dimensional loading and routing constraints with time windows. To solve this problem, for the first time a mixed‐integer linear programming model is formulated with considering practical last‐in‐first‐out loading constraints, and a branch‐and‐price‐based (BP‐based) heuristic is proposed based on a set partitioning formulation. In the heuristic, a modified labeling algorithm is proposed for the complex pricing problem, which is a relaxation of the elementary shortest path problem with resource constraints and two‐dimensional loading constraints. Therein, an effective Tabu‐maximum open space packing heuristic is proposed to verify the feasibility of the two‐dimensional packing problem of each route generated by the labeling algorithm. In addition, effective accelerating and branching strategies are introduced to improve the solving efficiency of the heuristic. To evaluate the effectiveness and the advantages of the proposed heuristic, extensive computational experiments are performed based on the generated instances. The computational results show that the proposed BP‐based heuristic can effectively solve the 2L‐CVRPTW, in which the optimal solutions can be achieved much faster than CPLEX in small‐scale problems. Relationships between the transportation cost and the characteristics of the instances are analyzed. The stability of the algorithm and the effectiveness of the accelerating strategies are verified and discussed

    Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast Cancer Detection

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    <div><p>Breast cancer is one of the most frequent and aggressive primary tumors among women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed in varieties of diseases including breast cancer. Therefore, noninvasive visualization and quantification of MMP <i>in vivo</i> are of great interest in basic research and clinical application for breast cancer early diagnosis. Herein, we developed a <sup>99m</sup>Tc labeled membrane type I matrix metalloproteinase (MT1-MMP) specific binding peptide, [<sup>99m</sup>Tc]-(HYNIC-AF7p)(tricine)(TPPTS), for <i>in vivo</i> detection of MDA-MB-231 breast tumor by single photon emission computed tomography (SPECT). [<sup>99m</sup>Tc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice biostability and high MT1-MMP binding affinity <i>in vitro</i> and <i>in vivo</i>. Tumor-to-muscle ratio was found to reach to the highest (4.17±0.49) at 2 hour after intravenously administration of [<sup>99m</sup>Tc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB-231 tumor bearing mice. Overall, [<sup>99m</sup>Tc]-(HYNIC-AF7P)(tricine)(TPPTS) demonstrated great potential for MT1-MMP targeted detection <i>in vivo</i> and it would be a promising molecular imaging probe that are probably beneficial to breast cancer early diagnoses.</p></div

    Cytotoxicity of AF7p analogs on MDA-MB-231 cells.

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    <p>No cytotoxicity was observed at different concentrations of AF7p, Cy5.5-AF7p and (HYNIC-AF7P)(tricine)(TPPTS).</p

    Fluorescent immunohistochemistry for MT1-MMP expression in MDA-MB-435 and A549 tumors.

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    <p>More MT1-MMP expressed in MDA-MB-435 tumor was observed than that of in A549 tumor. Green: FITC conjugated donkey anti-Rabbit secondary antibody. Blue: DAPI. All signals were adjusted to the same scale. Scale bar equals10 ÎŒm.</p

    Characterizations.

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    <p>(A) Chemical structure of [<sup>99m</sup>Tc]-(HYNIC-AF7p)(tricine)(TPPTS). (B) Radio-HPLC purity of [<sup>99m</sup>Tc]-(HYNIC-AF7p)(tricine)(TPPTS).</p

    Solution stability data for [<sup>99m</sup>Tc(HYNIC-AF7P)(tricine)(TPPTS)] in saline (A) and in the presence of excess cysteine (B) (1 mg/mL, pH = 7.4).

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    <p>Solution stability data for [<sup>99m</sup>Tc(HYNIC-AF7P)(tricine)(TPPTS)] in saline (A) and in the presence of excess cysteine (B) (1 mg/mL, pH = 7.4).</p
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