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AbstractIn this work, we examine port crane scheduling with spatial and separation constraints. Although common to most port operations, these constraints have not been previously studied. We assume that cranes cannot cross, there is a minimum distance between cranes and jobs cannot be done simultaneously. The objective is to find a crane‐to‐job matching which maximizes throughput under these constraints. We provide dynamic programming algorithms, a probabilistic tabu search, and a squeaky wheel optimization heuristic for solution. Experiments show the heuristics perform well compared with optimal solutions obtained by CPLEX for small scale instances where a squeaky wheel optimization with local search approach gives good results within short times. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004.

Zhao Huang,1,* Nan Ma,2,* Yan-Lu Xiong,1,* Lei Wang,1 Wei-Miao Li,1 Yuan-Yang Lai,1 Chen-Xi Zhang,1 Zhi-Pei Zhang,1 Xiao-Fei Li,1 Jin-Bo Zhao1 1Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, People's Republic of China; 2Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, People's Republic of China*These authors contributed equally to this workCorrespondence: Jin-Bo Zhao; Xiao-Fei LiDepartment of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Baqiao, Xi'an, Shaanxi 710038, People's Republic of ChinaTel +86 29 8471 7367Fax +86 29 8471 7367Email zhaojinbo@aliyun.com; lxfchest@fmmu.edu.cnPurpose: High metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms.Patients and methods: We investigate the expression of NOK, p-Akt, p-GSK-3β, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3β. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3β pathway.Results: Statistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3β (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3β. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3β pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3β pathway.Conclusion: Our results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3β/N-cadherin pathway in NSCLC.Keywords: NOK/STYK1, epithelial-mesenchymal transition, Akt, GSK3β, N-cadherin, non-small cell lung cancer

Beyond comparative genomics, we identified 85 sugar transporter genes in Cordyceps militaris, clustering into nine subfamilies as sequence- and phylogenetic-based functional classification, presuming the versatile capability of the fungal growths on a range of sugars. Further analysis of the global gene expression patterns of C. militaris showed 123 genes were significantly expressed across the sucrose, glucose, and xylose cultures. The sugar transporters specific for pentose were then identified by gene-set enrichment analysis. Of them, the putative pentose transporter, CCM_06358 gene, was highest expressed in the xylose culture, and its functional role in xylose transport was discovered by the analysis of conserved structural motifs. In addition, a battery of molecular modeling methods, including homology modeling, transport pathway analysis, residue interaction network combined with molecular mechanics Poisson–Boltzmann surface area simulation (MM-PBSA), was implemented for probing the structure and function of the selected pentose transporter (CCM_06358) as a representative of sugar transportome in C. militaris. Considering the network bottlenecks and structural organizations, we further identified key amino acids (Phe38 and Trp441) and their interactions with other residues, contributing the xylose transport function, as verified by binding free energy calculation. The strategy used herein generated remarkably valuable biological information, which is applicable for the study of sugar transportome and the structure engineering of targeted transporter proteins that might link to the production of bioactive compounds derived from xylose metabolism, such as cordycepin.