Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism

神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma

PETREL for Astrophysics and Carbon Business

A multi-purpose 50kg class microsatellite hosting astrophysical mission and earth remote sensing, PETREL , will be launched in 2023. In the night side, PETREL observe the ultra-violet sky with a wide-field telescope covering 50 deg^2 for surveying transient objects related to supernovae, tidal disruption events, and gravitational wave events. Our UV telescope can detect the early phase UV emission from a neutron star merger occurred within 150 Mpc. In addition to the satellite observation, PETREL sends a detection alert including the coordinate and brightness of the UV transient to the ground via the real time communication network within several minutes after detection to conduct follow-up observations with the collaborating ground based observatories over the world. In the day side, PETREL observes the surface of the earth by using the tunable multi-spectral cameras and a ultra-compact hyperspectral camera. Our potential targets are the tropical forests (Green Carbon) and coastal zones (Blue Carbon) in the tropical areas to evaluating the global biological carbon strages. For this purpose PETREL will conduct multiple scale mapping collaborating with drones and small aircraft not only satellite. The obtained data will be used for academical research and for business applications. The technical difficulty of this satellite is that carries out multi-purpose with different requirements, such as astronomical observations which requires a quite high attitude stability and the earth observations requiring a high pointing accuracy, with limited resources. If it is possible, a novel small satellite system or a business style can be realized that can share the payload with academia and industry. PETREL has been adopted as Innovative Satellite Technology Demonstration Program No.3 led by JAXA, and development is underway with the aim of launching in FY2023

Feasibility Study of Technology Demonstration Mission for Integrated Attitude-Orbit Control of Solar Sail

We are developing a micro solar sail called PIERIS . The purpose of this project is to demonstrate the following two world-first technologies in Low Earth Orbit. The first technology is to control the external torque with a single gimbal motor. It will be possible to achieve a completely propellant-free Integrated Attitude-Orbit Control. The second technology is a sail structure that guarantees the accuracy of the Pyramid-Shaped sail membrane shape and reduces disturbance torque caused by membrane surface deformation. This project has been selected for the Feasibility-Study phase of the JAXA Small Satellite Rush Program and is scheduled for launch in FY2026 if approved to proceed to the next phase. We are currently conducting mission and system feasibility studies and developing a Bread Board Model

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

Essays on market microstructure

The first essay analyzes the market microstructure of the European Climate Exchange (ECX), the largest European Union Emissions Trading Scheme trading venue. Spreads range from 2 to 6 times the minimum tick increment on European Union Allowances (EUA) futures. Market impact estimates imply that an average trade will move the EUA market by 1.08 euro centimes. Information shares imply that approximately 90% of price discovery is taking place in the ECX futures market. We find imbalances in the order book help predict returns for up to three days. A simple trading strategy that enters the market long or short when the order imbalance is strong is profitable even after accounting for spreads and market impact. The second essay provides a case that the Thompson-Waller (TW) estimator would have downward bias, which has not been carefully discussed in the literature. Such case is that (i) the buy (sell) order tends to follow buy (sell) order and (ii) the price changes associated to such orders are small. The upward bias of the TW estimator would be canceled out by the downward bias, and in such case the estimator would perform better than the other absolute price change methods. The application to the EUA futures contract trading implies that its trading pattern and the price change provide the conditions that reduce the bias of the TW estimator. The Madhavan, Richardson and Roomans model is applied to examine the spread component of the market. A dominance of asymmetric information component in the spread is found. The fraction of the spread attributable to that component increases gradually during the observation period. The final essay examines price discovery of Japanese companies' Tokyo-New York cross-listed shares. Kalman filter is utilized to estimate partial price adjustment model. By employing Kalman filter, the present research can deal with missing values problem researchers has to confront in order to analyze non-overlapping markets such as Tokyo and New York. I find that events with larger magnitude of efficient price change occur during Tokyo opening hours. Dynamic measure shows that New York Stock Exchange is more efficient in price discovery.Ph. D.Includes bibliographical referencesIncludes vitaby Yoichi Otsub