Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most commonly observed histologic subtype of esophageal cancer. ESCC is believed to develop via accumulation of numerous genetic alterations, including inactivation of tumor suppressor genes and activation of oncogenes. We searched for transcripts that were altered in human ESCC samples compared with nontumor tissues. METHODS: We performed integrative transcriptome sequencing (RNA-Seq) analysis using ESCC samples from 3 patients and adjacent nontumor tissues to identify transcripts that were altered in ESCC tissue. We performed molecular and functional studies of the transcripts identified and investigated the mechanisms of alteration. RESULTS: We identified protein tyrosine kinase 6 (PTK6) as a transcript that was significantly down-regulated in ESCC tissues and cell lines compared with nontumor tissues or immortalized normal esophageal cell lines. The promoter of the PTK6 gene was inactivated in ESCC tissues at least in part via hypermethylation and histone deacetylation. Knockdown of PTK6 in KYSE30 ESCC cells using small hairpin RNAs increased their ability to form foci, migrate, and invade extracellular matrix in culture and form tumors in nude mice. Overexpression of PTK6 in these cells reduced their proliferation in culture and tumor formation in mice. PTK6 reduced phosphorylation of Akt and glycogen synthase kinase (GSK)3β, leading to activation of β-catenin. CONCLUSIONS: PTK6 was identified as a transcript that is down-regulated in human ESCC tissues via epigenetic modification at the PTK6 locus. Its product appears to regulate cell proliferation by reducing phosphorylation of Akt and GSK3β, leading to activation of β-catenin. Reduced levels of PTK6 promote growth of xenograft tumors in mice; it might be developed as a marker of ESCC. © 2012 AGA Institute.link_to_subscribed_fulltex

Optimisation of schedules for the inspection of railway tracks

Inspection of railway tracks involves a high volume of short-duration tasks (e.g. visual inspection, vehicle-based inspection, measurement, etc.) each of which is repeated at different frequencies and time intervals. It is important to gain asmany benefits as possible from the inspection tasks, which incur huge expenses. To date, various optimisation methods have been incorporated into the schedule generation to determine an inspection order for a known number and geographical location of tracks. Due to the specific requirements of certain tracks or inspection problem—for example, the number of schedule parameters and one-off or incremental type schedules—researchers have developed moresophisticated and problem-dependent optimisation methods. However, introduction of a new inspection technology and policy in the last five years, especially in the United Kingdom, has urged a remodelling of the scheduling problem in track inspection in order to cope up with the new operational and business constraints. Thus, this paper conducts a review and gap analysis of previous studies with regard to track inspection scheduling problems from an optimisation point of view. In addition, the authors discuss several potential research interests resulting from the gap analysis undertaken. This studyshows that heuristic methods are popular among researchers in searching for an optimal schedule subject to single or multiple optimisation function(s) while satisfying various technical and business constraints