68 research outputs found
SBML Level 3: an extensible format for the exchange and reuse of biological models
Get PDFAbstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution
SBML Level 3: an extensible format for the exchange and reuse of biological models
Get PDFSystems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.journal articl
国際機構条約法条約における国際機構の法的地位に関する一考察(二・完) : 条約締結能力に対する制限と同意の有効性
No full text2000-12-25departmental bulletin pape
Synthesis of the D-3 Series of Phosphatidylinositol Phosphates
No full textThe 3-mono-, 3,4-bis-, and 3,4,5-trisphosphates of
l-α-phosphatidyl-d-myo-inositol
have been
synthesized in their optically active forms from the two enantiomers of
1,2:5,6-di-O-cyclohexylidene-myo-inositol. These chiral precursors were prepared by a
facile biocatalytic resolution, in which
the 4-butyryl ester of the racemic compound was subjected to
enantioselective hydrolysis by porcine
pancreatic lipase in a biphasic system. The overall yield from
individual chiral precursors ranged
from 32% for the 3,4,5-trisphosphate to 39% for the
monophosphate
Total Syntheses of the Histone Deacetylase Inhibitors Largazole and 2-<i>epi</i>-Largazole: Application of <i>N</i>-Heterocyclic Carbene Mediated Acylations in Complex Molecule Synthesis
No full textDetails of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting γ,δ-unsaturated-α,β-epoxy-aldehydes and a thiazole-thiazoline containing ω-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole’s structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the α-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines
Hieronymi Davidis Gaubii ... Libellus de methodo concinnandi formulas medicamentorum.
No full textMode of access: Internet.Sign.: *8, A-2E8, 2F4
Pharmacological Exploitation of the α1-Adrenoreceptor Antagonist Doxazosin to Develop a Novel Class of Antitumor Agents That Block Intracellular Protein Kinase B/Akt Activation
No full textThe α1-adrenoreceptor antagonist doxazosin induces apoptosis in malignant cells with moderate
potency via an α1-adrenoreceptor-independent mechanism. Here, we demonstrate that the
ability of doxazosin to induce apoptosis in PC-3 prostate cancer cells was, in part, attributable
to the inhibition of protein kinase B (PKB)/Akt activation. The separation of the effect of
doxazosin on apoptosis from its original pharmacological activity provides molecular underpinnings to develop novel antitumor agents. Replacement of the (2,3-dihydro-benzo[1,4]dioxane)-carbonyl moiety of doxazosin with aryl-sulfonyl functions dramatically improves the potency
in facilitating Akt deactivation and inducing apoptosis. The optimal compounds, 33 and 44,
were effective in apoptosis induction at low micromolar concentrations irrespective of androgen
dependency and p53 functional status. Both agents were active in suppressing the growth of
a panel of 60 cancer-cell lines with IC50 values of 2.2 and 1.5 μM, respectively. Together, these
in vitro efficacy data suggest the translational potential of these agents in prostate cancer
treatment
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