A Repot of Voluntary Action for Education

departmental bulletin pape

Observation of the DsJ(2317) and DsJ(2457) in B Decays

journal articl

ON EXISTENCE OF SOLUTIONS FOR THE UNILATERAL PROBLEM ASSOCIATED TO THE DEGENERATE KIRCHHOFF EQUATIONS

application/pdfLet ＄￥Omega＄ be a bounded domain in ＄￥mathbb{R}^{N}＄ with smooth boundary ＄￥Gamma,＄ ＄T＄ is a positive real number, ＄￥rho＄ : ＄[0, T]￥times￥overline{￥Omega}￥rightarrow ￥mathbb{R}＄ is a real function. In this paper, we consider the existence of solutions for the following nonlinear unilateral problem: ＄￥rho(t, x)u_{tt}(t, x)-||￥nabla u(t,x)||_{2}^{2￥gamma}￥Delta u(t, x)￥geq|u(t, x)|^{￥alpha}u(t,x)＄ on ＄[0, T]￥times￥Omega＄ , ＄u(t, x)=0＄ on ＄￥sum=[0, T]￥times￥Gamma＄ , ＄u(0, x)=u_{0}(x),＄ ＄u_{t}(0, x)=u_{1}(x)＄ on ＄￥Omega＄ , where ＄￥Delta＄ is the Laplacian in ＄￥mathbb{R}^{N},＄ ＄￥alpha>0＄ and ＄￥gamma￥geq 1＄ .departmental bulletin pape

Sparse Topological Pharmacophore Graphs for Interpretable Scaffold Hopping

The aim of scaffold hopping (SH) is to find compounds consisting of different scaffolds from those in already known active compounds, giving an opportunity for unexplored regions of chemical space. We previously demonstrated the usefulness of pharmacophore graphs (PhGs) for this purpose through proof-of-concept virtual screening experiments. PhGs consist of nodes and edges corresponding to pharmacophoric features (PFs) and their topological distances. Although PhGs were effective in SH, they are hard to interpret as they are complete graphs. Herein, we introduce an intuitive representation of a molecule, termed as sparse pharmacophore graphs (SPhG) by keeping the topological distances among PFs as much as possible while reducing the number of edges in the graphs. Several benchmark calculations quantitatively confirmed the sparseness of the graphs and the preservation of topological distances among pharmacophoric points. As proof-of-concept applications, virtual screening (VS) trials for SH were conducted using active and inactive compounds from ChEMBL and PubChem databases for three biological targets: thrombin, tyrosine kinase ABL1, and κ-opioid receptor. The performances of VS were comparable with using fully connected PhGs. Furthermore, highly ranked SPhGs were interpretable for the three biological targets, in particular for thrombin, for which selected SPhGs were in agreement with the structure-based interpretation.journal articl

Principle of the labeling of influenza vRNPs with transiently expressed NP-mCherry proteins.

Image is not to scale. Neither the real stoechiometry nor the spatial organization of a vRNP is represented. For clarity, only a single NP-mCherry incorporated into an RNP complex is shown, although incorporation of multiple NP-mCherry molecules per RNP might also occur.</p

FLIM-FRET microscopy in live HEK-293T cells.

<p>A. The principle of FLIM-FRET assay with GFP_comp and mCherry as the FRET donor and acceptor, respectively, is schematically drawn; a representative fluorescence decay dataset fitted curve (in red) and residuals for a single pixel within the nucleus of a cell infected with the WSN-PB2-GFP11 virus are shown. B. Fluorescence intensity (left and middle panels) and mean GFP_comp fluorescence lifetime (right panels) images of the infected and/or transfected cells. Graphs to the right of the micrographs show the distributions of mean GFP_comp fluorescence lifetime values (occurrence of pixels with a given mean lifetime) in the nuclei pointed by yellow arrowheads in GFP_comp intensity images (middle right panels). Sketches on the far right show the “observable”, fluorescently labeled species for each sample; virus ideographs indicate viral infection, either with WSN-wt (in positive and negative controls) or with WSN-PB2-GFP11 (in other infected samples).</p

Live Vero cells transfected with GFP1-10 and NP-mCherry and infected with the WSN-PB2-GFP11 virus.

Selected frames from S1 Movie at the indicated times post-infection are shown. Pseudocolors: green, PB2-GFPcomp; red, NP-mCherry. Scale bar, 10 μm. Time-lapse series of single optical slices were acquired with a Nipkow spinning disk microscope.</p

Colocalization of transiently expressed NP-mCherry with vRNPs in infected A549 cells.

<p>Mock-infected cells (top panels) or cells infected with the WSN-wt influenza virus (bottom panels) are shown. Cells were fixed at 6 hpi and stained with the anti-NP monoclonal antibody clone 3/1. Scale bar: 10 μm. Pseudocolors: red, mCherry; green, NP; blue, nuclei staining (DAPI).</p

Detection of proximity between NP-mCherry and vRNPs in infected cells by proximity ligation assay.

<p>The anti-NP monoclonal antibody 3/1 and a rabbit antibody recognizing mCherry were used. Maximal intensity projections of the z-stacks acquired with a laser scanning confocal microscope are shown. Scale bar: 10 μm. Pseudocolors: white, PLA signal; red, mCherry; blue, nuclei staining (DAPI).</p

Fluorescence correlation spectroscopy data for PB2-GFP_comp- and NP-mCherry-labeled species in the nuclei of HEK-293T cells.

<p>Fluorescence correlation spectroscopy data for PB2-GFP_comp- and NP-mCherry-labeled species in the nuclei of HEK-293T cells.</p