Retinoblastoma gene mutations in primary human bladder cancer.

Inactivation of the retinoblastoma (RB) gene is known to be implicated in the pathogenesis of several types of human cancers. Since structural alterations of the RB gene have not been well examined in human bladder cancer, we looked for mutations in the entire coding region of this gene using polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis of RNA. We also examined allelic loss of the RB gene using PCR-based restriction fragment length polymorphism analysis. Of 30 samples obtained from patients with bladder cancer, eight (27%) were found to have RB gene mutations. DNA sequencing of the PCR products revealed five cases with single point mutations and three cases with small deletions. These mutations included one (10%) of ten low-grade (grade 1) tumours, four (50%) of eight intermediate-grade (grade 2) tumours and three (25%) of 12 high-grade (grade 3) tumours. Likewise, mutations were found in four (21%) of 19 superficial (pTa and pT1) tumours and four (36%) of 11 invasive (pT2 or greater) tumours. In 15 informative cases, loss of heterozygosity at the RB locus was shown in five cases (33%), three cases with RB mutations and two without them. These results suggest that RB gene mutations are involved in low-grade and superficial bladder cancers as well as in high-grade and invasive cancers

Gravitational waveforms for 2- and 3-body gravitating systems

Different numbers of self-gravitating particles (in different types of periodic motion) are most likely to generate very different shapes of gravitational waves, some of which, however, can be accidentally almost the same. One such example is a binary and a three-body system for Lagrange's solution. To track the evolution of these similar waveforms, we define a chirp mass to the triple system. Thereby, we show that the quadrupole waveforms cannot distinguish the sources. It is suggested that waveforms with higher $\ell$-th multipoles will be important for classification of them (with a conjecture of $\ell \leq N$ for N particles).Comment: 11 pages, 4 figures, accepted for publication in PR

CAMELOT: Design and performance verification of the detector concept and localization capability

A fleet of nanosatellites using precise timing synchronization provided by the Global Positioning System is a new concept for monitoring the gamma-ray sky that can achieve both all-sky coverage and good localization accuracy. We are proposing this new concept for the mission CubeSats Applied for MEasuring and LOcalising Transients (CAMELOT). The differences in photon arrival times at each satellite are to be used for source localization. Detectors with good photon statistics and the development of a localization algorithm capable of handling a large number of satellites are both essential for this mission. Large, thin CsI scintillator plates are the current candidates for the detectors because of their high light yields. It is challenging to maximize the light-collection efficiency and to understand the position dependence of such thin plates. We have found a multi-channel readout that uses the coincidence technique to be very effective in increasing the light output while keeping a similar noise level to that of a single channel readout. Based on such a detector design, we have developed a localization algorithm for this mission and have found that we can achieve a localization accuracy better than 20 arc minutes and a rate of about 10 short gamma-ray bursts per year

CAMELOT: Cubesats Applied for MEasuring and LOcalising Transients mission overview

We propose a fleet of nanosatellites to perform an all-sky monitoring and timing based localisation of gamma-ray transients. The fleet of at least nine 3U cubesats shall be equipped with large and thin CsI(Tl) scintillator based soft gamma-ray detectors read out by multi-pixel photon counters. For bright short gamma-ray bursts (GRBs), by cross-correlating their light curves, the fleet shall be able to determine the time difference of the arriving GRB signal between the satellites and thus determine the source position with an accuracy of similar to 10'. This requirement demands precise time synchronization and accurate time stamping of the detected gamma-ray photons, which will be achieved by using on-board GPS receivers. Rapid follow up observations at other wavelengths require the capability for fast, nearly simultaneous downlink of data using a global inter-satellite communication network. In terms of all-sky coverage, the proposed fleet will outperform all GRB monitoring missions

Identification of a novel human memory T cell population with the characteristics of stem-like chemo-resistance

我々は新しいヒトCD8+免疫記憶T幹細胞であるYoung memory T（TYM）細胞を同定した。TYM細胞は高い増殖能，多分化能，抗がん剤耐性を持ちウイルス免疫および癌免疫に関わっている。TYM細胞の制御が今後の免疫療法の効果の増強に重要と考える

CubeSats in Support of Astrophysics, GRBAlpha and Beyond

Space science, including the field of astrophysics, is continuously finding innovative use cases for small satellites and CubeSat platforms. These missions support efforts in the democratisation and improved accessibility of space technologies. GRBAlpha, as one of such missions, is a 1U CubeSat carrying an experimental payload for the detection of gamma-ray bursts (GRB)

Extreme longevity variants at the FOXO3 locus may moderate FOXO3 isoform levels

This is the final version. Available on open access from Springer via the DOI in this recordThe rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive assessment of FOXO3 isoform usage across a wide variety of human tissues and carried out a bioinformatic analysis of the potential for longevity-associated variants to disrupt regulatory regions involved in isoform choice. We then related the expression of full length and 5' truncated FOXO3 isoforms to rs13217795 genotype in peripheral blood and skeletal muscle from individuals of different rs13217795 genotypes. FOXO3 isoforms displayed considerable tissue specificity. We determined that rs13231195 and its tightly aligned proxy variant rs9400239 may lie in regulatory regions involved in isoform choice. The longevity allele at rs13217795 was associated with increased levels of full length FOXO3 isoforms in peripheral blood and a decrease in truncated FOXO3 isoforms in skeletal muscle RNA. We suggest that the longevity effect of FOXO3 SNPs may in part derive from a shift in isoform usage in skeletal muscle away from the production of 5' truncated FOXO3 isoforms lacking a complete forkhead DNA binding domain, which may have compromised functionality.National Institute for Health Research (NIHR)Kuakini Medical Center, the US National Institutes of HealthNational Heart, Lung, and Blood InstituteUniversity of Exete