6,018 research outputs found

    Tetrazine-Triggered Release of Carboxylic-Acid-Containing Molecules for Activation of an Anti-inflammatory Drug.

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    In addition to its use for the study of biomolecules in living systems, bioorthogonal chemistry has emerged as a promising strategy to enable protein or drug activation in a spatially and temporally controlled manner. This study demonstrates the application of a bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction to cleave trans-cyclooctene (TCO) and vinyl protecting groups from carboxylic acid-containing molecules. The tetrazine-mediated decaging reaction proceeded under biocompatible conditions with fast reaction kinetics (<2 min). The anti-inflammatory activity of ketoprofen was successfully reinstated after decaging of the nontoxic TCOprodrug in live macrophages. Overall, this work expands the scope of functional groups and the application of decaging reactions to a new class of drugs

    Targeting cancer cells overexpressing folate receptors with new terpolymer-based nanocapsules: Toward a novel targeted dna delivery system for cancer therapy

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    Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies

    Misuse and Artifact in Factor Analytic Research

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    The theory of factor analysis has been developed for incorporating mathematical statistical theories such as the maximum likelihood method and asymptotic methods. However, there have been several instances of misuse while employing procedures for factor analysis studies. In several studies, factor analysis has been performed by deleting items exhibiting the ceiling effect or floor effect. The number of samples required for factor analysis is not well known. Kaiser-Guttman criterion cannot be applied for determining the number of factors. Furthermore, various studies have employed Scree Graphs and Parallel Analysis for the said purpose, but no definitive method exists for the same. Orthogonal rotation methods such as Varimax cannot be considered as a conclusive solution. However, Geomin has been considered as a better rotation method not only for simple structure but also for more complex factor configuration. Simple structure and bifactor structure are discussed in connection to factor rotation problem. Although there are various artifacts associated with the usage of factor analysis, this issue can be addressed by verifying factorial invariance through multi-group simultaneous analysis incorporated by SEM programs such as Mplus and R Package.因子分析の理論は、最尤法と漸近的方法のような数理統計学的理論を組み込んだ形で発展してきた。しかしながら、因子分析研究の手順にはまだ誤用がみられる。いくつかの研究において、天井効果や床効果を示す項目を削除して因子分析が行われている。因子分析に必要なサンプル数は明確ではない。因子の数を決定するためにKaiser-Guttman 基準は使うことはできない。そして、この目的でScree Graph とParallel Analysis を使用している研究は数多くあるが、そのための決定的な方法はない。Varimax のような直交回転は最終的な解と考えることはできない。しかしながら、Geomin は単純構造だけでなくより複雑な因子の布置に対しても優れた回転方法と考えられている。因子回転問題を考慮した単純構造とbifactor 構造について議論した。因子分析の使い方には多くのartifacts があるが、この問題は、Mplus やR Package などのSEMプログラムによって組み込まれた複数集団の同時分析によって因子的不変性を検証することによって対処することができる

    The Microchannel X-ray Telescope for the Gamma-Ray Burst mission SVOM

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    We present the Microchannel X-ray Telescope, a new light and compact focussing telescope that will be flying on the Sino-French SVOM mission dedicated to Gamma-Ray Burst science. The MXT design is based on the coupling of square pore micro-channel plates with a low noise pnCCD. MXT will provide an effective area of about 50 cmsq, and its point spread function is expected to be better than 3.7 arc min (FWHM) on axis. The estimated sensitivity is adequate to detect all the afterglows of the SVOM GRBs, and to localize them to better then 60 arc sec after five minutes of observation.Comment: 12 pages, 8 figures, to be published in SPIE Astronomical Telescopes + Instrumentation, Montreal, June 201

    Semi-kinematic mount of the FIREBALL large optics

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    In the context of the NASA CNES FIREBALL balloon borne experiment, we present the design of a semi-kinematic mount to hold the 1 meter class mirrors of this mission. To maintain these large optics in a reasonable mass and price budgets we choose thin ULE mirrors with a thickness over diameter ratio of 1/16. Such thin mirrors require a multi support mount to reduce self weight deflection. Classical multi support mount used for ground based telescope would not survive the level of shock observed in a balloon experiment either at parachute opening or landing. To firmly maintain these mirrors in several points without noticeably deforming them we investigated the design of a two stages semi-kinematic mount composed of 24 monopods. We present the detailed design of this innovative mirror mount, the finite element modeling with the deduced optical wavefront deformation. During the FIREBALL integration and flight campaign in July 2007 at CSBF, we confirmed the validity of the mechanical concept by obtaining an image quality well within the required specifications. Variants of this approach are potentially applicable to large thin mirrors on ground-based observatories

    Tuning Carbon Dioxide Adsorption Affinity of Zinc(II) MOFs by Mixing Bis(pyrazolate) Ligands with N-Containing Tags

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    The four zinc(II) mixed-ligand metal-organic frameworks (MIXMOFs) Zn(BPZ)x(BPZNO2)1-x, Zn(BPZ)x(BPZNH2)1-x, Zn(BPZNO2)x(BPZNH2)1-x, and Zn(BPZ)x(BPZNO2)y(BPZNH2)1-x-y (H2BPZ = 4,4′-bipyrazole; H2BPZNO2 = 3-nitro-4,4′-bipyrazole; H2BPZNH2 = 3-amino-4,4′-bipyrazole) were prepared through solvothermal routes and fully investigated in the solid state. Isoreticular to the end members Zn(BPZ) and Zn(BPZX) (X = NO2, NH2), they are the first examples ever reported of (pyr)azolate MIXMOFs. Their crystal structure is characterized by a three-dimensional open framework with one-dimensional square or rhombic channels decorated by the functional groups. Accurate information about ligand stoichiometric ratio was determined (for the first time on MIXMOFs) through integration of selected ligands skeleton resonances from 13C cross polarized magic angle spinning solid-state NMR spectra collected on the as-synthesized materials. Like other poly(pyrazolate) MOFs, the four MIXMOFs are thermally stable, with decomposition temperatures between 708 and 726 K. As disclosed by N2 adsorption at 77 K, they are micro-mesoporous materials with Brunauer-Emmett-Teller specific surface areas in the range 400-600 m2/g. A comparative study (involving also the single-ligand analogues) of CO2 adsorption capacity, CO2 isosteric heat of adsorption (Qst), and CO2/N2 selectivity in equimolar mixtures at p = 1 bar and T = 298 K cast light on interesting trends, depending on ligand tag nature or ligand stoichiometric ratio. In particular, the amino-decorated compounds show higher Qst values and CO2/N2 selectivity vs the nitro-functionalized analogues; in addition, tag "dilution" [upon passing from Zn(BPZX) to Zn(BPZ)x(BPZX)1-x] increases CO2 adsorption selectivity over N2. The simultaneous presence of amino and nitro groups is not beneficial for CO2 uptake. Among the compounds studied, the best compromise among uptake capacity, Qst, and CO2/N2 selectivity is represented by Zn(BPZ)x(BPZNH2)1-x