The Mus81–Eme1 complex is a structure-specific endonuclease that preferentially cleaves nicked Holliday junctions, 3′-flap structures and aberrant replication fork structures. Mus81−/− mice have been shown to exhibit spontaneous chromosomal aberrations and, in one of two models, a predisposition to cancers. The molecular mechanisms underlying its role in chromosome integrity, however, are largely unknown. To clarify the role of Mus81 in human cells, we deleted the gene in the human colon cancer cell line HCT116 by gene targeting. Here we demonstrate that Mus81 confers resistance to DNA crosslinking agents and slight resistance to other DNA-damaging agents. Mus81 deficiency spontaneously promotes chromosome damage such as breaks and activates the intra-S-phase checkpoint through the ATM-Chk1/Chk2 pathways. Furthermore, Mus81 deficiency activates the G2/M checkpoint through the ATM-Chk2 pathway and promotes DNA rereplication. Increased rereplication is reversed by the ectopic expression of Cdk1. Haploinsufficiency of Mus81 or Eme1 also causes similar phenotypes. These findings suggest that a complex network of the checkpoint pathways that respond to DNA double-strand breaks may participate in some of the phenotypes associated with Mus81 or Eme1 deficiency.

This paper deals with the bias correction of the cross-validation (CV) criterion to estimate the predictive Kullback-Leibler information.A bias-corrected CV criterion is proposed by replacing the ordinary maximum likelihood estimator with the maximizer of the adjusted log-likelihood function. The adjustment is just slight and simple, but the improvement of the bias is remarkable. The bias of the ordinary CV criterion is O(n −1 ), but that of the bias-corrected CV criterion is O(n −2 ). We verify that our criterion has smaller bias than the AIC, TIC, EIC and the ordinary CV criterion by numerical experiments.

Sulfur mustard, an agent used in chemical warfare, is an alkylating substance with carcinogenic potential. However, the precise long-term carcinogenic effects of mustard gas are unclear. Since 1952, the authors have conducted health surveys of former workers who were employed from 1929 to 1945 in a poisonous gas factory in Okuno-jima, Hiroshima, Japan. This prospective study was undertaken from 1952 to 2005 to examine the incidence of lung cancer among the workers who were exposed to mustard gas (n=480), lewisite (n=55), and/or diphenylcyanarsine (n=178), as well as the incidence among unexposed workers (n=969). The stochastic relation between exposure and lung cancer was explored on the basis of multistage carcinogenesis by using an accelerated hazard model with a transformed age scale. Mustard gas exposure was found to transform the age scale for developing lung cancer. One year of exposure in subjects ≤18 or >18 years old at first exposure shifted the age scale down by 4.9 years and 3.3 years, respectively. On the basis of the long-term follow-up of former workers in the poisonous gas factory, the authors concluded that sulfur mustard decreased the age at which people were at risk of developing lung cancer and that the effect declined with aging.

There is a need for accurate dosimetry for studies of health effects in the Japanese atomic bomb survivors because of the important role that these studies play in worldwide radiation protection standards. International experts have developed dosimetry systems, such as the Dosimetry System 2002 (DS02), which assess the initial radiation exposure to gamma rays and neutrons but only briefly consider the possibility of some minimal contribution to the total body dose by residual radiation exposure. In recognition of the need for an up-to-date review of the topic of residual radiation exposure in Hiroshima and Nagasaki, recently reported studies were reviewed at a technical session at the 57th Annual Meeting of the Health Physics Society in Sacramento, California, 22-26 July 2012. A one-day workshop was also held to provide time for detailed discussion of these newer studies and to evaluate their potential use in clarifying the residual radiation exposures to the atomic-bomb survivors at Hiroshima and Nagasaki. Suggestions for possible future studies are also included in this workshop report.