Cyclin D1, an oncogenic G1 cyclin, and YB-1, a transcription factor involved in cell growth, are both over-expressed in several human cancers. In human lung cancer, the functional association between YB-1 and cyclin D1 has never been elucidated. In this study, we show YB-1 is involved in the transcription of cyclin D1 in human lung cancer. Depletion of endogenous YB-1 by siRNA inhibited progression of G1 phase and down-regulated both the protein and mRNA levels of cyclin D1 in human lung cancer cells. Forced over-expression of YB-1 with a cyclin D1 reporter plasmid increased luciferase activity, and ChIP assay results showed YB-1 bound to the cyclin D1 promoter. Moreover, the amount of YB-1 mRNA positively correlated with cyclin D1 mRNA levels in clinical non-small-cell lung cancer (NSCLC) specimens. Immunohistochemical analysis also indicated YB-1 expression correlated with cyclin D1 expression in NSCLC specimens. In addition, most of the cases expressing both cyclin D1 and CDC6, another molecule controlled by YB-1, had co-existing YB-1 over-expression. Together, our results suggest that aberrant expression of both cyclin D1 and CDC6 by YB-1 over-expression may collaboratively participate in lung carcinogenesis.

Y box binding protein 1 (YB1) has multiple functions associated with drug resistance, cell proliferation and metastasis through transcriptional and translational regulation. Increased expression of YB1 is closely related to tumor growth and aggressiveness. We showed that YB1 protein levels were decreased through replicative and premature senescence and were correlated with increased expression levels of p16INK4A tumor suppressor gene. Depletion of YB1was associated with increased levels of p16 in human and murine primary cells. Forced expression of YB1 in mouse embryonic fibroblasts resulted in decreased expression of p16 and increased cell proliferation. Senescence-associated expression of b-galactosidase was repressed in YB1-over-expressing cells. Chromatin immunoprecipitation assays showed that YB1 directly associates with the p16 promoter. Taken together, all our findings indicate that YB1 directly binds to and represses p16 transcription, subsequently resulting in the promotion of cell growth and prevention of cellular senescence.

Methods of theoretical simulations of noncontact atomic force microscopy in liquids have been developed. Though there are several difficult issues for the theoretical simulations in liquids, the authors introduce here the simulation methods for the cantilever oscillation in liquids and the tip-sample interaction force mediated by water molecules. As for the cantilever motion, a very efficient numerical method is proposed which solves the oscillation of the elastic beam cantilever and fluid dynamics simultaneously. The results reproduce fairly well the resonant curve and related properties of the Si beam cantilever. As for the simulation of the tip-sample interaction force in water, classical molecular dynamics (MD) method is adopted in the present work. The case study by MD for the mica surface in water revealed new features that appeared in the three-dimensional force map.

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BackgroundFor achieving equity of the accessibility to primary healthcare, measuring potential geographical accessibility is essential. The provider-to-population ratio is the most frequently used measure. However, it is difficult to be used in closer region because it does not take into consideration the people and health services beyond its boundary. In order to overcome this problem, we measured the potential access to hospital, using both distance measures and the enhanced two-step floating catchment area (E2SFCA) method. The aim of this study was to compare the number of hospitals in the neighborhood and the E2SFCA score with regard to the amount and equity for access to hospitals.MethodsThis descriptive study used publicly available data from 2010. The E2SFCA score and number of neighborhood hospitals were obtained from Tochigi province in Japan using a geographic information system. Dataset of four measures by each census tract was obtained. The measures were E2SFCA score, number of hospitals within the 5 km range, number of hospitals within the 10 km range, and number of hospitals within the 15 km range. Correlation and disparity analyses with the Lorenz curve and Gini coefficient were performed.ResultsThe measures were obtained in a smaller area than municipality considering adjacent areas using a geographical approach. The E2SFCA score was 5.3 [3.2–7.3] hospitals/million (median [quantile range]), compared to 5.6 hospitals/million in total for the given district. The median number of hospitals within the 5 km, 10 km, and 15 km ranges were 1, 39, and 47, respectively. There was no hospital within the 5 km range in one third of the blocks. Both the number of hospitals within the 10 km range and those within the 15 km range were well correlated. Regional difference became smaller as the distance to count the number of hospitals increased. The gap between small number of hospitals and the high E2SFCA score indicated the location of community hospital in depopulated areas.ConclusionsThe E2SFCA method is superior for analyzing spatial access to hospital, because it provides information in the closer sub-regions. Regional differences were hardly seen in access to hospital beyond the 10 km range. Further studies in other regions and countries are needed for precise assessment.

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Today's web is so huge and diverse that it arguably reflects the real world. For this reason, searching the web is a promising approach to find things in the real world. This paper presents NEXAS, an extension to web search engines that attempts to find real-world entities relevant to a topic. Its basic idea is to extract proper names from the web pages retrieved for the topic. A main advantage of this approach is that users can query any topic and learn about relevant realworld entities without dedicated databases for the topic. In particular, we focus on an application for finding authoritative people from the web. This application is practically important because once personal names are obtained, they can lead users from the web to managed information stored in digital libraries. To explore effective ways of finding people, we first examine the distribution of Japanese personal names by analyzing about 50 million Japanese web pages. We observe that personal names appear frequently on the web, but the distribution is highly influenced by automatically generated texts. To remedy the bias and find widely acknowledged people accurately, we utilize the number of web servers containing a name instead of the number of web pages. We show its effectiveness by an experiment covering a wide range of topics. Finally, we demonstrate several examples and suggest possible applications.

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