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Takashi Mitamura,1 Tianyue Zhai,1 Kanako C Hatanaka,2 Yutaka Hatanaka,2,3 Toraji Amano,4 Lei Wang,5,6 Shinya Tanaka,5,6 Hidemichi Watari1 1Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 2Center for Development of Advanced Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 3Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 4Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan; 5Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Hokkaido, Japan; 6Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, JapanCorrespondence: Takashi Mitamura, Department of Obstetrics and Gynecology, Hokkaido University Faculty of Medicine, Hokkaido University, North15, West 7, Kita-Ku, Sapporo, 0608638, Hokkaido, Japan, Tel +81 11 706 5941, Fax +81 11 706 7711, Email takami@huhp.hokudai.ac.jpPurpose: To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients.Patients and Methods: DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III–IV ovarian cancer with no recurrence for 8– 23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role.Results: The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the PRDM1 gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group.Conclusion: Germline heterozygous rs2185379 in PRDM1 is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.Keywords: ovarian cancer, long-term survivors, rs2185379, PRDM1

The system in this article was operated for electric heating and thermal storage, thermal storage and desiccant cooling, three days of controlled system operation, and a one-day actual outdoor air conditions operation. Results show that almost 9 h of electric heating is needed to store sufficient thermal energy and that same thermal stored energy is barely enough to support the desiccant cooling operation for only 7 h. It is also shown that excess thermal energy in the tank from the previous day's operation cannot support the early-hour desiccant cooling the following day. [ABSTRACT FROM AUTHOR]

Suppressing the stress corrosion cracking (SCC) by reducing the carbon content in austenitic stainless steels is apparently not effective on core shrouds used in boiling water reactors in Japan: trans-granular cracking was found in the shrouds. To clarify the mechanism of the cracking, in situ stress measurements on specimens under stretched conditions in hot water have been attempted in the present study. An in situ device for diffraction measurements at synchrotron radiation facilities has been developed, and in situ experiments have been carried out at SPring-8. The SUS316L steel specimen was solution heat-treated, surface-ground and then placed in the in situ device. Sapphire windows were used for the light path in the device. A sufficient diffracted beam intensity was obtained through two sapphire windows and water. The side-inclination method was used for measuring the stress exerted on the specimen. A 2θ–sin2ψ plot showed that a tensile stress was induced. The measured stress value is considered to be the summation of stresses owing to pre-straining, in situ loading and residual stress owing to surface grinding. [ABSTRACT FROM AUTHOR]

Austenitic stainless steel specimens of type 316SS were irradiated by 200 keV He+ ions or 200 keV N+ ions. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to study the fine surface deformation of the irradiated specimens. At the high temperatures of He+ ion irradiation, distinct swelling was observed at grain interior and grain boundaries by AFM and helium bubbles were found by TEM. It is suggested that helium atoms agglomerate in high doses and high temperatures. The nanometer-level step height of surface swelling induced by He+ ion irradiation has obvious dependence on the irradiation dose and temperature. In the case of N+ ion irradiation, the swelling was observed at grain interior but the step height was less remarkable than in the case of He+ ions. The swelling is induced by void formation. The caved-in grain boundaries were recognized in N+ ion irradiated area. [ABSTRACT FROM AUTHOR]

The article reports that gouty arthritis is rarely encountered in Down's syndrome regardless of persistent hyperuricaemia. In a survey by researchers Robert W. Fuller and others, twenty out of forty patients with Down's syndrome had high serum urate levels (more than 7 mg per 100 ml). The researchers also found the presence of hyperuricaemic Down's syndrome, but found no gouty patients. Only one case of Down's syndrome associated with gout was recently documented by them. The patients with Down's syndrome have a shorter life-span and comparatively mild hyperuricaemia might explain the low incidence of gout.

The combination of atovaquone and proguanil (Malarone™, GlaxoSmithKline) has been established as an effective drug of choice not only for treatment but also for prophylaxis of multi-drug resistant Plasmodium falciparum malaria in travellers. However, several cases of resistance against Malarone™ have already been reported in some parts of Africa, and many of the cases are associated with mutations at codon 268 of cytochrome b gene in mitochondrial genome of P. falciparum. On the contrary, in Asian countries, only limited numbers of clinical failures with the drug has so far been reported, and no mutations could be found at the codon 268. To maintain the usefulness of Malarone™ in travel medicine, monitoring of the effectiveness of the drug is needed. In this study, mutations of atovaquone binding site on the cytochrome b were investigated by PCR amplification and sequencing of the gene (1131bp length) in the parasites from patients at the Hospital for Tropical Diseases Mahidol University in Bangkok, Thailand, in 2002 through 2005. Twenty-five blood samples were from complicated falciparum malaria patients and another 25 were from non-complicated falciparum patients who were infected in multi-drug resistant areas in Thai-Myanmar border. Forty-seven out of 50 samples were successfully analyzed, and no mutation was observed in putative ubiquinol (Q 0) binding site 1 and 2. In fact, they showed identically conserved nucleotide sequences, as was reported by our previous study conducted in the same area in 1999. We may conclude from these findings that Malarone™ is still effective and recommended for treatment and prophylaxis for travellers to Mekong region. [Copyright &y& Elsevier]