VLBI astrometry on the white dwarf pulsar AR Scorpii

AR Scorpii (AR Sco), the only-known radio-pulsing white dwarf binary, shows unusual pulsating emission at the radio, infrared, optical, and ultraviolet bands. To determine its astrometric parameters at the radio band independently, we conducted multi-epoch Very Long Baseline Interferometry (VLBI) phase-referencing observations with the European VLBI Network at 5 GHz and the Chinese VLBI Network plus the Warkworth 30-m telescope (New Zealand) at 8.6 GHz. By using the differential VLBI astrometry, we provide high-precision astrometric measurements on the parallax (pi = 8.52(-0.07)(+0.04) mas) and proper motion (mu(alpha) = 9.48(-0.07)(+0.04) mas yr(-1), mu(delta) = -51.32(-0.38)(+0.22) mas yr (-1)). The new VLBI results agree with the optical Gaia astrometry. Our kinematic analysis reveals that the Galactic space velocities of AR Sco are quite consistent with that of both intermediate polars and polars. Combined with the previous tightest VLBI constraint on the size, our parallax distance suggests that the radio emission of AR Sco should be located within the light cylinder of its white dwarf

FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model

Background: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. Methods: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)-a major target of FTY720. The binding of the endogenous inhibitor SET to PP2A in presence of FTY720 was evaluated by immunoblotting and immunoprecipitation. Signaling and activation of programmed cell death were evaluated by immunoblotting and flow cytometry. A syngeneic mouse model was used to evaluate anti-tumor efficacy and toxicity profile of FTY720 in vivo. Results: We show that FTY720 significantly suppressed MM cell viability and anchorage-independent growth without affecting normal HM cells. FTY720 inhibited the phosphatase activity of PP2A by displacement of SET protein, which appeared overexpressed in MM, as compared to HM cells. FTY720 promoted AKT dephosphorylation and Bcl-2 degradation, leading to induction of programmed cell death, as demonstrated by caspase-3 and PARP activation, as well as by cytochrome c and AIF intracellular translocation. Moreover, FTY720 administration in vivo effectively reduced tumor burden in mice without apparent toxicity. Conclusions: Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment

Studi Potensi Jumlah Penumpang Bus Pemadu Moda Rute Malang – Bandar Udara Juanda Pp

Bandar Udara Malang yang belum melayani banyak tujuan penerbangan membuat pengguna moda pesawat memilih Bandar Udara Juanda. Disisi lain angkutan yang melayani rute Malang-Juanda PP hanya angkutan travel. Untuk itu dibutuhkan moda lain yang lebih ekonomis dan memiliki kapasitas lebih banyak dibandingkan angkutan travel. Bus pemadu moda adalah moda alternatif yang dapat memenuhi kebutuhan tersebut.Pengumpulan data dilakukan dengan penyebaran kuisioner karakteristik sosial-ekonomi, karakteristik perjalanan serta kuisioner dengan teknik penyusunan stated preference. Stated preference memiliki atribut biaya perjalanan, waktu tempuh dan frekuensi keberangkatan. Sedangkan untuk prediksi tarif bus pemadu moda yang direncanakan diperoleh dari perhitungan BOK. Tarif yang telah diperoleh dari perhitungan BOK dibandingkan dengan nilai ATP dan WTP yang diperoleh dari kuisioner yang telah disebarkan. Sehingga didapatkan tarif ideal yang akan diberlakukan apabila bus pemadu moda tersebut direalisasikan.Setelah melakukan perhitungan tarif berdasarkan BOK diperoleh tarif sebesar Rp 23.374,- serta berdasarkan ATP dan WTP diperoleh tarif sebesar Rp 43.675,-. Dengan demikian perkiraan awal tarif bus pemadu moda sebesar Rp 40.000,- dapat diberlakukan. Hasil dari pemodelan pemilihan moda dengan metode stated preference untuk selisih biaya perjalanan Malang-Juanda: dan Juanda-Malang : , untuk selisih waktu tempuh perjalanan () rute Malang-Juanda : dan rute Juanda-Malang : , sedangkan untuk selisih Frekuensi Keberangkatan () rute Malang-Juanda : dan rute Juanda-Malang : .Potensi perpindahan pengguna travel ke bus pemadu moda rute Malang-Juanda sebanyak 705 orang per hari (83,97%). Sedangkan untuk rute Juanda-Malang sebanyak 1516 orang per hari (90,24%)

EAVN Astrometry toward the Extreme Outer Galaxy: Kinematic distance with the proper motion of G034.84-00.95

We aim to reveal the structure and kinematics of the Outer-Scutum-Centaurus (OSC) arm located on the far side of the Milky Way through very long baseline interferometry (VLBI) astrometry using KaVA, which is composed of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We report the proper motion of a 22 GHz H$_{2}$O maser source, which is associated with the star-forming region G034.84$-$00.95, to be ($\mu_{\alpha} \rm{cos}\delta$, $\mu_{\delta}$) = ($-$1.61$\pm$0.18, $-$4.29$\pm$0.16) mas yr$^{-1}$ in equatorial coordinates (J2000). We estimate the 2D kinematic distance to the source to be 18.6$\pm$1.0 kpc, which is derived from the variance-weighted average of kinematic distances with LSR velocity and the Galactic-longitude component of the measured proper motion. Our result places the source in the OSC arm and implies that G034.84$-$00.95 is moving away from the Galactic plane with a vertical velocity of $-$38$\pm$16 km s$^{-1}$. Since the H I supershell GS033+06$-$49 is located at a kinematic distance roughly equal to that of G034.84$-$00.95, it is expected that gas circulation occurs between the outer Galactic disk around G034.84$-$00.95 with a Galactocentric distance of 12.8$^{+1.0}_{-0.9}$ kpc and halo. We evaluate possible origins of the fast vertical motion of G034.84$-$00.95, which are (1) supernova explosions and (2) cloud collisions with the Galactic disk. However, neither of the possibilities are matched with the results of VLBI astrometry as well as spatial distributions of H II regions and H I gas.Comment: Accepted for publication in PASJ. 14 figures; 8 table

Co(III)/Zn(II)-catalyzed dearomatization of indoles and coupling with carbenes from ene-yne ketones via intramolecular cyclopropanation

A straightforward and efficient protocol for dearomatizing indoles is described. The reaction, catalyzed by an inexpensive Co(III)/Zn(II) catalyst, starts from easily accessible N-pyrimidinyl indoles and ene-yne ketones. Mild reaction conditions, high diastereoselectivity, a broad substrate scope, effective functional group tolerance, and reasonable to remarkable yields were observed. (C) 2018, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved

coiiizniicatalyzeddearomatizationofindolesandcouplingwithcarbenesfromeneyneketonesviaintramolecularcyclopropanation

二氢吲哚骨架被广泛用作不对称合成中的关键结构单元和手性助剂,也广泛存在于具有多种生物活性的生物碱和其他天然产物中.其中2,3位取代的吲哚啉衍生物因其存在的广泛性和生物活性良好而备受关注.手性环丙烷可通过开环或环扩展转化为有价值的合成中间体,构建类似天然产物Lundurines的包含三个季碳立体中心的二氢吲哚并环丙烷结构是很有吸引力的目标.传统构建此类化合物的方法包括过渡金属催化和经典的Simmons-Smith反应等.然而,更有效、环境友好和原子经济性的生成卡宾前体的催化方法研究仍然非常有限.目前由羰基炔化合物和锌盐催化合成多功能性锌-呋喃卡宾的研究引起了人们的关注.而Cp*Co(III)由于其地球丰度、成本效益、低毒性和独特的催化活性已引起越来越多的注意,但Cp*Co(III)作为路易斯酸用于催化反应的报道仍然较少.本文报道了吲哚与烯炔酮通过Zn(II)/Co(III)呋喃卡宾可以实现分子内环丙烷化,得到一系列具有三维环状结构的二氢吲哚化合物.研究从Co(III)/Zn(II)催化N-嘧啶吲哚与烯炔酮偶联反应开始,条件筛选实验验证了Co(III)/Zn(II)催化联合使用的强大功能.反应体系中不加Co(III)导致目标产物的痕量形成,而排除Zn(II)会使收率降低.本文共完成了30个不同官能团取代的二氢吲哚并环丙烷骨架结构的合成,目标产物收率从中等到良好,最高收率可达94%.反应有较好的普适性,吲哚基底物不局限于N-吡啶,N-酰基反应也进行得很顺利,达到90%的收率.为了提高反应的实用性,我们进行了放大实验.结果表明,当嘧啶吲哚用量由0.2增大至5 mmol时,反应仍能以较高的收率(90%)得到目标产物.此外,目标产物还可以进一步衍生转化为其他杂环类化合物,如在Pd(PPh3)4作用下发生Suzuki偶联反应.总之,我们在Co(III)/Zn(II)催化下成功实现了吲哚的分子内环丙烷化,合成了一系列含有三个季碳立体中心的二氢吲哚并环丙烷化合物,为新药开发奠定了基础.该催化体系反应条件温和,底物适用范围广,非对映体选择性高,催化效率高

coiiizniicatalyzeddearomatizationofindolesandcouplingwithcarbenesfromeneyneketonesviaintramolecularcyclopropanation

二氢吲哚骨架被广泛用作不对称合成中的关键结构单元和手性助剂,也广泛存在于具有多种生物活性的生物碱和其他天然产物中.其中2,3位取代的吲哚啉衍生物因其存在的广泛性和生物活性良好而备受关注.手性环丙烷可通过开环或环扩展转化为有价值的合成中间体,构建类似天然产物Lundurines的包含三个季碳立体中心的二氢吲哚并环丙烷结构是很有吸引力的目标.传统构建此类化合物的方法包括过渡金属催化和经典的Simmons-Smith反应等.然而,更有效、环境友好和原子经济性的生成卡宾前体的催化方法研究仍然非常有限.目前由羰基炔化合物和锌盐催化合成多功能性锌-呋喃卡宾的研究引起了人们的关注.而Cp*Co(III)由于其地球丰度、成本效益、低毒性和独特的催化活性已引起越来越多的注意,但Cp*Co(III)作为路易斯酸用于催化反应的报道仍然较少.本文报道了吲哚与烯炔酮通过Zn(II)/Co(III)呋喃卡宾可以实现分子内环丙烷化,得到一系列具有三维环状结构的二氢吲哚化合物.研究从Co(III)/Zn(II)催化N-嘧啶吲哚与烯炔酮偶联反应开始,条件筛选实验验证了Co(III)/Zn(II)催化联合使用的强大功能.反应体系中不加Co(III)导致目标产物的痕量形成,而排除Zn(II)会使收率降低.本文共完成了30个不同官能团取代的二氢吲哚并环丙烷骨架结构的合成,目标产物收率从中等到良好,最高收率可达94%.反应有较好的普适性,吲哚基底物不局限于N-吡啶,N-酰基反应也进行得很顺利,达到90%的收率.为了提高反应的实用性,我们进行了放大实验.结果表明,当嘧啶吲哚用量由0.2增大至5 mmol时,反应仍能以较高的收率(90%)得到目标产物.此外,目标产物还可以进一步衍生转化为其他杂环类化合物,如在Pd(PPh3)4作用下发生Suzuki偶联反应.总之,我们在Co(III)/Zn(II)催化下成功实现了吲哚的分子内环丙烷化,合成了一系列含有三个季碳立体中心的二氢吲哚并环丙烷化合物,为新药开发奠定了基础.该催化体系反应条件温和,底物适用范围广,非对映体选择性高,催化效率高

Integrated analysis of transcriptome-wide m6A methylation in a Cd-induced kidney injury rat model

Background: Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in a variety of diseases. However, the specific functions of m6A in CdCl2-induced kidney injury remain unclear. Objective: Here, we investigate a transcriptome-wide map of m6A modifications and explore the effects of m6A on Cd-induced kidney injury. Materials and methods: The rat kidney injury model was constructed by subcutaneous injection of CdCl2 (0.5, 1.0, and 2.0 mg/kg). The m6A levels were measured by colorimetry. The level of expression of m6A-related enzymes were detected by reverse transcription quantitative real-time PCR analysis. Transcriptome-wide m6A methylome in CdCl2 (2.0 mg/kg) and the control group were profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Subsequently, the sequencing data were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) confirmed the functional enrichment pathways of sequencing genes. In addition, a protein-protein interaction (PPI) network was applied to select hub genes. Results: The levels of m6A and m6A regulators (METTL3, METTL14, WTAP, YTHDF2) were significantly increased in CdCl2 groups. We identified a total of 2615 differentially expressed m6A peaks, 868 differentially expressed genes and 200 genes with significant changes in both m6A modification and gene expression levels. GO, KEGG, and GSEA analyses indicated that these genes were mainly enriched in inflammation and metabolism-related pathways such as in IL-17 signaling and fatty acid metabolism. According the result of the conjoint analysis, we identified the top ten hub genes (Fos, Hsp90aa1, Gata3, Fcer1g, Cftr, Cspg4, Atf3, Cdkn1a, Ptgs2, and Npy) which may be regulated by m6A and involve in CdCl2-induced kidney damage. Conclusion: This study established a m6A transcriptional map in a CdCl2-induced kidney injury model and suggested that m6A may affect CdCl2 induced kidney injury via regulated the inflammation and metabolism related gene