Multiband gravitational-wave event rates and stellar physics

Joint gravitational-wave detections of stellar-mass black-hole binaries by ground- and space-based observatories will provide unprecedented opportunities for fundamental physics and astronomy. We present a semianalytic method to estimate multiband event rates by combining selection effects of ground-based interferometers (like LIGO/Virgo) and space missions (like LISA). We forecast the expected number of multiband detections first by using information from current LIGO/Virgo data, and then through population synthesis simulations of binary stars. We estimate that few to tens of LISA detections can be used to predict mergers detectable on the ground. Conversely, hundreds of events could potentially be extracted from the LISA data stream using prior information from ground detections. In general, the merger signal of binaries observable by LISA is strong enough to be unambiguously identified by both current and future ground-based detectors. Therefore third-generation detectors will not increase the number of multiband detections compared to LIGO/Virgo. We use population synthesis simulations of isolated binary stars to explore some of the stellar physics that could be constrained with multiband events, and we show that specific formation pathways might be overrepresented in multiband events compared to ground-only detections.Comment: 17 pages, 11 figures. Database and python code available at https://github.com/dgerosa/spops - Published in PR

Integrative understanding of biological processes mediated by transient macromolecular complexes; New technology for visualizing physiologically metastable states

金沢大学 フロンティアサイエンス機構核膜孔複合体(NPC)は、核-細胞質間でのタンパク質、RNA等の選択的物質輸送を制御している(橋爪ら 生化学 2011)。30種類以上あるNPCタンパク質の一つRae1(RNA export factorl)は、Nup98と共にRNAを輸送することが知られている。最近の研究ではいくつかのヌクレオポリンの中には紡錘体形成、及び、有糸分裂後期開始に影響を与え、細胞の癌化に関与するものがあることが明らかになってきた(Funasaka and Wong, Cancer Metasta Rev 2011; Nakano et al., Cell Cycle 2011)。一方、研究代表者は最近、Rae1がNuMA及びSMC1と相互作用することを見出し、この相互作用の変化が多くの癌で見いだされる染色体の異数化・多極紡錘体を引き起こすことを発見した。そこで本研究課題では、Rae1-Nup98の細胞質-核間輸送、及び有糸分裂期中の詳細な機能を分子細胞生物学、及び、構造生物学の両側面から理解することを目的とした。当該年度は、急性骨髄性白血病(AML)細胞中の染色体転座に多くみられるキメラタンパク質Nup98/HoxA9を解析した。通常Nup98は、間期では核膜孔に、有糸分裂期では紡錘体に局在するが、キメラタンパク質Nup98/HoxA9は、間期では核内に、有糸分裂期では染色体上に局在が変化していた。これらのデータをまとめ論文を発表した(Funasaka et. al., Cell Cycle 2011)。また、核膜孔複合体の構造と機能についての総説を生化学に(橋爪ら 生化学 2011)、ヌクレオポリンの一つNup88についての総説を生体の科学にて発表した(橋爪ら 生体の科学2011)。さらに、AKTAタンパク質精製装置を用いて高純度のRae1タンパク質を精製することに成功することができた。研究課題/領域番号:22121506, 研究期間(年度):2010 – 201

Rae1の動態と機能の解析

金沢大学多くの癌では染色体異数体といった染色体異常が見られるが、癌悪性化における異数体発生機序やその役割については未だよくわかっていない。細胞有糸分裂における正常な染色体分離のメカニズムを知ることは、癌悪性化を引き起こす染色体不安定を理解するのに必須である。核膜孔複合体は核膜上にあって細胞質と核の間の分子の交換を制御するものであり、最近この核膜孔複合体を介した巨大分子の核内外への輸送が有糸分裂に深く関わっていることが明らかになってきた。この複合体はヌクレオポリンと呼ばれるタンパク質の集合によって構成されている。その中の一つであるRaelは核と細胞質間の分子の輸送に重要であり、また有糸分裂に関与する微小管に結合することが示されている。申請者はこのRaelが分裂期の微小管重合体に結合し、NuMAと相互作用して紡錘体極の形成に関与していることを明らかにしており、さらに最近cohesinのサブユニットであるSMC1とも相互作用して染色体の正常な分離に深く関与していることを見いだした(PNAS, 105:15441-5,2008)。申請者は現在も引き続きRaelについての検討を継続しており、他ヌクレオポリン(Nup88、Nup98など)との相互作用や、また新たに他ヌクレオポリンについての解析も進めている。申請者の研究室では、順調に研究が進むとともに次々と新しい展開が出てきており、実験道具消耗品、新しい設備備品など、多額の研究費が必要となっている。しかしながら、現在の経済状況ではこれらを買い揃えるには、申請者が新規に取得した科研費若手研究(B)を併せても、厳しいと言わざるを得ない。近年Raelの過剰発現が乳癌患者で確認されたり、ヌクレオポリン遺伝子(Nup98)の異常が関係する白血病は難治性であると報告されるなど、核膜孔複合体の欠陥と癌との関係が示唆されている。本研究はこれらの見解と併せ考えても、基礎生物学及び臨床医学の両面から重要な課題であると思われる。研究課題/領域番号:20890083, 研究期間(年度):2008出典：研究課題「Rae1の動態と機能の解析」課題番号20890083（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-20890083/）を加工して作

Characterization of the role of the tumor marker Nup88 in mitosis

Nuclear pore complexes are massive multiprotein channels responsible for traffic between the nucleus and cytoplasm, and are composed of approximately 30 proteins, termed nucleoporins (Nup). Our recent studies indicated that the nucleoporins Rae1 and Tpr play critical roles in maintaining the spindle bipolarity during cell division. In the present study, we found that another nucleoporin, Nup88, was localized on the spindles together with Nup214 during mitosis. Nup88 expression is linked to the progression of carcinogenesis, Nup88 has been proposed as a tumor marker. Overexpression of Nup88 enhanced multinucleated cell formation. RNAi-mediated knockdown of Nup88 disrupted Nup214 expression and localization and caused multipolar spindle phenotypes. Our data indicate that proper expression of Nup88 is critical for preventing aneuploidy formation and tumorigenesis

Carbon nanotube switches for memory, RF communications and sensing applications, and methods of making the same

Switches having an in situ grown carbon nanotube as an element thereof, and methods of fabricating such switches. A carbon nanotube is grown in situ in mechanical connection with a conductive substrate, such as a heavily doped silicon wafer or an SOI wafer. The carbon nanotube is electrically connected at one location to a terminal. At another location of the carbon nanotube there is situated a pull electrode that can be used to elecrostatically displace the carbon nanotube so that it selectively makes contact with either the pull electrode or with a contact electrode. Connection to the pull electrode is sufficient to operate the device as a simple switch, while connection to a contact electrode is useful to operate the device in a manner analogous to a relay. In various embodiments, the devices disclosed are useful as at least switches for various signals, multi-state memory, computational devices, and multiplexers

The role of nuclear pore complex in tumor microenvironment and metastasis

金沢大学フロンティアサイエンス機構One of the main reasons for cancer mortality is caused by the highly invasive behavior of cancer cells, which often due to aggressive metastasis. Metastasis is mediated by various growth factors and cytokines, operating through numerous signaling pathways. Remarkably, all these metastatic signaling pathways must enter the nucleus through a single gatekeeper, the nuclear pore complex (NPC). NPCs are the only gateway between the cytoplasm and the nucleus. NPCs are among the largest proteinaceous assemblies in the cell and are composed of multiple copies of around 30 different proteins called nucleoporins. Here, we review what is currently known about the NPC, and its role in the mechanisms of tumor progression. We will also explore potential strategies to target metastatic pathways by manipulating the karyopherins (importins/exportins) of nucleocytoplasmic traffic through NPCs. © 2011 Springer Science+Business Media, LLC

Magnetic Properties of Linear Chain Systems: Metamagnetism of Single Crystal Co(pyridine)\u3csub\u3e2\u3c/sub\u3eCl\u3csub\u3e2\u3c/sub\u3e

The metamagnetic behavior of the low temperature properties of single crystal Co(pyridine)2Cl2 is discussed. At 1.25 K oriented single crystals exhibit a two‐step metamagnetic transition at applied fields ∼0.8 and 1.6 kG along the b‐axis, a single transition at ∼0.7 kG for applied fields along the a∗ axis, and a single transition at ∼4.2 kG for an applied field along the c axis. Just above the transition fields a moment of 2μB/Co atom is measured for B0 parallel to the a∗ axis or b axis, and 0.4μB/Co atom is measured for the B0 parallel to the c axis. A large field dependent moment is observed at high fields. Many features of this compound closely mirror the behavior of CoCl2⋅2H2O. However, the Co(pyridine)2Cl2 has a much smaller interchain exchange, so that many features can be examined at lower fields. The basic features are consistent with a six‐sublattice model for the ordered antiferromagnetic system. Measurements of magnetic moment versus temperature show that Co(pyridine)2Cl2 does not obey a Curie–Weiss law even at relatively high temperatures

Ataluren treatment of patients with nonsense mutation dystrophinopathy

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double-blind, placebo-controlled study; males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need

Regulation of autophagy by nucleoporin Tpr

The nuclear pore complex (NPC) consists of a conserved set of ∼30 different proteins, termed nucleoporins, and serves as a gateway for the exchange of materials between the cytoplasm and nucleus. Tpr (translocated promoter region) is a component of NPC that presumably localizes at intranuclear filaments. Here, we show that Tpr knockdown caused a severe reduction in the number of nuclear pores. Furthermore, our electron microscopy studies indicated a significant reduction in the number of inner nuclear filaments. In addition, Tpr siRNA treatment impaired cell growth and proliferation compared to control siRNA-treated cells. In Tpr-depleted cells, the levels of p53 and p21 proteins were enhanced. Surprisingly, Tpr depletion increased p53 nuclear accumulation and facilitated autophagy. Our study demonstrates for the first time that Tpr plays a role in autophagy through controlling HSP70 and HSF1 mRNA export, p53 trafficking with karyopherin CRM1, and potentially through direct transcriptional regulation of autophagy factors. © 2012 Macmillan Publishers Limited. All rights reserved