3,367 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

    Cobalt(II) Bipyrazolate Metal-Organic Frameworks as Heterogeneous Catalysts in Cumene Aerobic Oxidation: A Tag-Dependent Selectivity

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    "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c00481"[EN] Three metal-organic frameworks with the general formula Co(BPZX) (BPZX(2-) = 3-X-4,4'-bipyrazolate, X = H, NH2, NO2) constructed with ligands having different functional groups on the same skeleton have been employed as heterogeneous catalysts for aerobic liquid-phase oxidation of cumene with O-2 as oxidant. O-2 adsorption isotherms collected at p(O2) = 1 atm and T = 195 and 273 K have cast light on the relative affinity of these catalysts for dioxygen. The highest gas uptake at 195 K is found for Co(BPZ) (3.2 mmol/g (10.1 wt % O-2)), in line with its highest BET specific surface area (926 m(2)/g) in comparison with those of Co(BPZNH(2)) (317 m(2)/g) and Co(BPZNO(2)) (645 m(2)/g). The O-2 isosteric heat of adsorption (Q(2)) trend follows the order Co(BPZ) > Co(BPZNH(2)) > Co(BPZNO(2)). Interestingly, the selectivity in the cumene oxidation products was found to be dependent on the tag present in the catalyst linker: while cumene hydroperoxide (CHP) is the main product obtained with Co(BPZ) (84% selectivity to CHP after 7 h, p(O2) = 4 bar, and T = 363 K), further oxidation to 2-phenyl-2-propanol (PP) is observed in the presence of Co(BPZNH(2)) as the catalyst (69% selectivity to PP under the same experimental conditions).S.G., R.V., and M.M. acknowledge Universita dell'Insubria for partial funding. G.G. thanks the Italian MIUR through the PRIN 2017 Project Multi-e: Multielectron Transfer for the Conversion of Small Molecules: an Enabling Technology for the Chemical Use of Renewable Energy (20179337R7) for financial support. G.G. thanks the TRAINER project (Catalysts for Transition to Renewable Energy Future) ref. ANR-17-MPGA-0017 for support. C.P. thanks the University of Camerino and the Italian MIUR throughout the PRIN 2015 Project Towards a Sustainable Chemistry (20154 x 9ATP_002). This project has also received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 641887 (project acronym: DEFNET) and the Spanish Government through projects MAT2017-82288-C2-1-P and Severo Ochoa (SEV-2016-0683). Professor Norberto Masciocchi (University of Insubria, Como, Italy) is acknowledged for fruitful discussions. 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    Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

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    The Standard Model predictions for WγW\gamma and ZγZ\gamma production are tested using an integrated luminosity of 200 pb1^{-1} of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the WW and ZZ bosons, and photons with transverse energy ET>7E_T>7 GeV that are well separated from leptons. The production cross sections and kinematic distributions for the WγW\gamma and ZγZ\gamma are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

    Measurement of the Lifetime Difference Between B_s Mass Eigenstates

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    We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion
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