57 research outputs found

    カンキョウケイエイ ト ジョウホウギジュツ ノ ソウゴサヨウ ニヨル シンカ ノ ケンキュウ

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    本稿は、企業における環境問題について、経営と情報技術を対象にしている。まず、「企業を取り巻く環境問題はどのように変化を遂げてきたか」を踏まえて、先行研究の環境経営の概念(コンセプト)を整理した上で「環境経営がどのような歴史的変遷と進化を辿り、進化の要因は何か、またその中で経営戦略の重要性がどのように高まってきたか」について検討を加える。続いて、環境問題と科学技術の関わりを述べた上で、「情報技術が他の技術に比べてどのような特質があり、それが環境経営にどのような影響を与えたか」、「情報技術の環境経営への先進活用にはどのような事例があるか」を論究する。そして、環境経営と情報技術がどのように影響を相互に与えて進化をしてきたのかを明らかにする。分析及び考察にあたっては、環境経営が進化する上で、経営上のニーズが情報技術の活用を必要とし(環境経営→技術(情報技術))、シーズとしての情報技術がそれにどのように応えてきたか(情報技術→環境経営)について焦点を当てた。そして、環境経営と情報技術の相互作用による浸透が環境経営の進化をもたらしていることを明らかにし、併せて情報技術を環境負荷の減少に使うか増大に使うかは、使うものの知恵に大きく依存していることを示す

    C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers

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    Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration

    Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

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    Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial

    Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]

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    Sequence-Specific Recognition of Double-Stranded DNA by Using Only PNAs in Parallel with Natural Nucleobases

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    The sequence-specific recognition of double-stranded DNA (dsDNA) is a key property for the control of DNA function. Peptide nucleic acid (PNA) can be utilised for the direct recognition of dsDNA via the formation of a unique invasion complex. Strand invasion by PNA induces local changes in the structure of dsDNA and is useful for the regulation of gene expression and genome editing. However, the fact that nucleobases modification is required for efficient invasion, has stymied the wide-spread application of PNA. Herein, we succeeded in the efficient recognition of target dsDNA sequences via formation of invasion complex by utilising only parallel-stranded and unmodified PNAs. This approach also streamlines synthesis by permitting the use of a peptide synthesiser rather than the manual synthesis we had been dependent upon for nucleobase-modified PNAs. Our new method also exhibited high sequence specificity and flexibility for target dsDNA sequences

    Extracellular Signal-Regulated Protein Kinase 2 Is Required for Efficient Generation of B Cells Bearing Antigen-Specific Immunoglobulin G

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    Activation of extracellular signal-regulated protein kinase (ERK) has been implicated in proliferation as well as differentiation in a wide variety of cell types. Using B-cell-specific gene-targeted mice, we report here that in T-cell-dependent immune responses, ERK2 is required to generate efficient immunoglobulin G (IgG) production. In its absence, the proportion of antigen-specific surface IgG1-bearing cells and the subsequent number of IgG1 antibody-secreting cells were decreased, despite apparently unimpaired class switch recombination. Notably, this defect was countered by overexpression of the antiapoptotic factor Bcl-2. Together, our results suggest that ERK2 plays a key role in efficient generation of antigen-specific IgG-bearing B cells by promoting their survival

    Effect of relativistically intense laser pulse in a tokamak plasma: Results of scaled simulations and experiments in cold gas limit

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    Existing methods for diagnostics and control are still insufficient to deal with the various kinds of instabilities and collective dynamics that occur in magnetically confined fusion plasmas, which may impact the missions of the ITER and DEMO projects. Using small-scale laser experiments on J-KAREN-P, numerical simulations on the JFRS-1 supercomputer and theoretical analyses, we are investigating whether short pulses (ps-fs) of a high power laser (TW-PW) may be used to address some of these issues. The object of interest is the electron-free positively charged plasma wake channel that is carved out by a laser pulse with relativistic intensity. Using the relativistic PIC codes EPOCH and REMP, we simulate the long-time evolution of such wake channels in the presence of a strong magnetic field (~2T) as is typical for tokamaks. We demonstrate that there exists a parameter window where the after-glow dynamics of the magnetized wake channels are effectively independent of the laser wavelength. This justifies scaled simulations with artificially increased wavelengths, which reduces the computational expenses to the point where long-time 3D simulations become feasible. We compare the results of recent 2D and 3D simulations and examine the effects of the plasma density and magnetic field strength via parameter scans. In particular, we will report our observations regarding particle acceleration, charge separation and the generation of magnetic vortices. First insights concerning the role of thermal motion will be discussed along with possible implications for tokamak plasma control and diagnostics.5th Kyoto U.-UNIST Worksho
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