Iterative algorithm for lane reservation problem on transportation network

International audienceIn this paper, we study an NP-hard lane reservation problem on transportation network. By selecting lanes to be reserved on the existing transportation network under some special situations, the transportation tasks can be accomplished on the reserved lanes with satisfying the condition of time or safety. Lane reservation strategy is a flexible and economic method for traffic management. However, reserving lanes has impact on the normal traffic because the reserved lanes can only be passed by the special tasks. It should be well considered choosing reserved lanes to minimize the total traffic impact when applying the lane reservation strategy for the transportation tasks. In this paper, an integer linear program model is formulated for the considered problem and an optimal algorithm based on the cut-and-solve method is proposed. Some new techniques are developed for the cut-and-solve method to accelerate the convergence of the proposed algorithm. Numerical computation results of 125 randomly generated instances show that the proposed algorithm is much faster than a MIP solver of commercial software CPLEX 12.1 to find optimal solutions on average computing time

Design of a Multiobjective Reverse Logistics Network Considering the Cost and Service Level

Reverse logistics, which is induced by various forms of used products and materials, has received growing attention throughout this decade. In a highly competitive environment, the service level is an important criterion for reverse logistics network design. However, most previous studies about product returns only focused on the total cost of the reverse logistics and neglected the service level. To help a manufacturer of electronic products provide quality postsale repair service for their consumer, this paper proposes a multiobjective reverse logistics network optimisation model that considers the objectives of the cost, the total tardiness of the cycle time, and the coverage of customer zones. The Nondominated Sorting Genetic Algorithm II (NSGA-II) is employed for solving this multiobjective optimisation model. To evaluate the performance of NSGA-II, a genetic algorithm based on weighted sum approach and Multiobjective Simulated Annealing (MOSA) are also applied. The performance of these three heuristic algorithms is compared using numerical examples. The computational results show that NSGA-II outperforms MOSA and the genetic algorithm based on weighted sum approach. Furthermore, the key parameters of the model are tested, and some conclusions are drawn

Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes

Comparative toxicoproteogenomics of mouse and rat liver identifies TCDD-resistance genes

The aryl hydrocarbon receptor (AHR) mediates many toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the AHR alone does not explain the widely different outcomes among organisms. To identify the other factors involved, we evaluated three transgenic mouse lines, each expressing a different rat AHR isoform (rWT, DEL, and INS) providing widely different resistance to TCDD toxicity, as well as C57BL/6 and DBA/2 mice which exhibit a similar to tenfold divergence in TCDD sensitivity (exposures of 5-1000 mu g/kg TCDD). We supplement these with whole-genome sequencing, together with transcriptomic and proteomic analyses of the corresponding rat models, Long-Evans (L-E) and Han/Wistar (H/W) rats (having a similar to 1000-fold difference in their TCDD sensitivities; 100 mu g/kg TCDD), to identify genes associated with TCDD-response phenotypes. Overall, we identified up to 50% of genes with altered mRNA abundance following TCDD exposure are associated with a single AHR isoform (33.8%, 11.7%, 5.2% and 0.3% of 3076 genes altered unique to rWT, DEL, C57BL/6 and INS respectively following 1000 mu g/kg TCDD). Hepatic Pxdc1 was significantly repressed in all three TCDD-sensitive animal models (C57BL/6 and rWT mice, and L-E rat) after TCDD exposure. Three genes, including Cxxc5, Sugp1 and Hgfac, demonstrated different AHRE-1 (full) motif occurrences within their promoter regions between rat strains, as well as different patterns of mRNA abundance. Several hepatic proteins showed parallel up- or downward alterations with their RNAs, with three genes (SNRK, IGTP and IMPA2) showing consistent, strain-dependent changes. These data show the value of integrating genomic, transcriptomic and proteomic evidence across multi-species models in toxicologic studies.Peer reviewe