75 research outputs found

    Molecular mechanisms driving the microgels behaviour: a Raman spectroscopy and Dynamic Light Scattering study

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    Responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) exhibit peculiar behaviours due to the competition between the hydrophilic and hydrophobic interactions of the constituent networks. The interpenetration of poly-acrilic acid (PAAc), a pH-sensitive polymer, within the PNIPAM network, to form Interpenetrated Polymer Network (IPN) microgels, affects this delicate balance and the typical Volume-Phase Transition (VPT) leading to complex behaviours whose molecular nature is still completely unexplored. Here we investigate the molecular mechanism driving the VPT and its influence on particle aggregation for PNIPAM/PAAc IPN microgels by the joint use of Dynamic Light Scattering and Raman Spectroscopy. Our results highlight that PNIPAM hydrophobicity is enhanced by the interpenetration of PAAc promoting interparticle interactions, a crossover concentration is found above which aggregation phenomena become relevant. Moreover we find that, at variance with PNIPAM, for IPN microgels a double-step molecular mechanisms occurs upon crossing the VPT, the first involving the coil-to-globule transition typical of PNIPAM and the latter associated to PAAc steric hindrance.Comment: preprint versio

    The role of iron in anthracycline cardiotoxicity

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    The clinical use of the antitumor anthracycline Doxorubicin is limited by the risk of severe cardiotoxicity. The mechanisms underlying anthracycline-dependent cardiotoxicity are multiple and remain uncompletely understood, but many observations indicate that interactions with cellular iron metabolism are important. Convincing evidence showing that iron plays a role in Doxorubicin cardiotoxicity is provided by the protecting efficacy of iron chelation in patients and experimental models, and studies showing that iron overload exacerbates the cardiotoxic effects of the drug, but the underlying molecular mechanisms remain to be completely characterized. Since anthracyclines generate reactive oxygen species, increased iron-catalyzed formation of free radicals appears an obvious explanation for the aggravating role of iron in Doxorubicin cardiotoxicity, but antioxidants did not offer protection in clinical settings. Moreover, how the interaction between reactive oxygen species and iron damages heart cells exposed to Doxorubicin is still unclear. This review discusses the pathogenic role of the disruption of iron homeostasis in Doxorubicin-mediated cardiotoxicity in the context of current and future pharmacologic approaches to cardioprotection

    Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2

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    Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involvedSupplementary Information: Supplementary Data 1; Supplementary Data 2; Reporting Summary.NHMRC; Women’s and Children’s Hospital Research Foundation; Muir Maxwell Trust; Epilepsy Society; The European Fund for Regional Development; The province of Friesland, Dystonia Medical Research Foundation; Stichting Wetenschapsfonds Dystonie Vereniging; Fonds Psychische Gezondheid; Phelps Stichting; The Italian Ministry of Health; Istituto Superiore di Sanità, Italy; Undiagnosed Disease Network Italy; The Fondation maladies rares, University Hospital Essen and UK Department of Health’s NIHR.https://www.nature.com/ncommspm2020Neurolog

    Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission

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    NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense

    Magnetic Force-Free Theory: Nonlinear Case

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    In this paper, a theory of force-free magnetic field useful for explaining the formation of convex closed sets, bounded by a magnetic separatrix in the plasma, is developed. This question is not new and has been addressed by many authors. Force-free magnetic fields appear in many laboratory and astrophysical plasmas. These fields are defined by the solution of the problem ∇×B=ΛB with some field conditions B∂Ω on the boundary ∂Ω of the plasma region. In many physical situations, it has been noticed that Λ is not constant but may vary in the domain Ω giving rise to many different interesting physical situations. We set Λ=Λ(ψ) with ψ being the poloidal magnetic flux function. Then, an analytic method, based on a first-order expansion of ψ with respect to a small parameter α, is developed. The Grad–Shafranov equation for ψ is solved by expanding the solution in the eigenfunctions of the zero-order operator. An analytic expression for the solution is obtained deriving results on the transition through resonances, the amplification with respect to the gun inflow. Thus, the formation of spheromaks or protosphera structure of the plasma is determined in the case of nonconstant Λ

    1-D Modeling of the Screw-Pinch Plasma in PROTO-SPHERA

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    A simple steady-state model for a 3-species mixture (ions, electrons, and neutrals) in a screw-pinch plasma configuration is developed. The model is applied to the central plasma column of the PROTO-SPHERA experiment. Degree of ionization, azimuthal current density, and azimuthal ion velocity are calculated. Full ionization is found at plasma temperatures above 1.5 eV, with neutrals confined in an outer shell where radial plasma flow develops and drives both azimuthal current and azimuthal flow

    Analysis of MHD instabilities by asymptotic methods

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    The m = 1 resistive mode for a tokamak plasma with large aspect ratio is considered: the dynamic equations in a resistive layer are solved by means of an asymptotic expansion for values of the growth rate in a suitable range. The eigenvalues characterizing the perturbation are found by means of a series expansion and it is shown that the main contribution to the expression of the eigenvalues is given by the first and the second order of this expansion. This method is different from the one used in the paper [G. Ara et al., Ann. Phys. 112, 443 (1978)], and can be applied in more general situations

    Gli effetti dinamici del moto delle campane: il caso del campanile di San Francesco a Pietrasanta

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    Il moto oscillatorio delle campane è in grado di provocare effetti di notevole entità sulle strutture che le accolgono, specialmente se queste si trovano in cattivo stato di conservazione e presentano fenomeni di dissesto. Una valutazione preliminare di queste conseguenze può essere eseguita per mezzo di trattazioni analitiche, dalle quali è possibile conoscere le caratteristiche principali del moto oscillatorio e le azioni che i bronzi sono in grado di trasmettere alle strutture. Dopo un’adeguata fase preliminare di acquisizione informazioni, i campanili possono essere studiati attraverso modelli di calcolo agli elementi finiti, al fine di conoscerne lo stato di salute globale e le proprietà dinamiche. Per mezzo di ulteriori trattazioni analitiche e agli elementi finiti è possibile conoscere gli effetti che il sistema oscillatorio genera sulla struttura di supporto, in modo da valutare la necessità di analisi approfondite, oltre che di eventuali strategie d’intervento
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