549 research outputs found

    Biochemodynamic features of metal ions bound by micro- and nano-plastics in aquatic media

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    A simple model, based on spherical geometry, is applied to the description of release kinetics of metal species from nano- and micro-plastic particles. Compiled literature data show that the effective diffusion coefficients, Deff, for metal species within plastic polymer bodies are many orders of magnitude lower than those applicable for metal ions in bulk aqueous media. Consequently, diffusion of metal ions in the aqueous medium is much faster than that within the body of the plastic particle. So long as the rate of dissociation of any inner-sphere metal complexes is greater than the rate of diffusion within the particle body, the latter process is the limiting step in the overall release kinetics of metal species that are sorbed within the body of the plastic particle. Metal ions that are sorbed at the very particle/medium interface and/or associated with surface-sorbed ligands do not need to traverse the particle body and thus in the diffusion-limiting case, their rate of release will correspond to the rate of diffusion in the aqueous medium. Irrespective of the intraparticulate metal speciation, for a given diffusion coefficient, the proportion of metal species released from plastic particles within a given time frame increases dramatically as the size of the particle decreases. The ensuing consequences for the chemodynamics and bioavailability of metal species associated with plastic micro- and nano-particles in aquatic systems are discussed and illustrated with practical examples

    Sensitizing thermochemotherapy with a PARP1-inhibitor

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    Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects

    Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia

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    Background: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results: The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods: Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of γ-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions: Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status

    Energy dependence of exclusive J/ψJ/\psi photoproduction off protons in ultra-peripheral p-Pb collisions at sNN\sqrt{s_{\rm{NN}}} = 5.02 TeV

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    The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of J/ψJ/\psi vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02\sqrt{s_{\rm NN}} = 5.02 TeV. The e+^+e^- and μ+μ\mu^+\mu^- decay channels are used to measure the cross section as a function of the rapidity of the J/ψJ/\psi in the range 2.5<y<2.7-2.5 < y < 2.7, corresponding to an energy in the γ\gammap centre-of-mass in the interval 40<Wγp<55040 < W_{\gamma\mathrm{p}}<550 GeV. The measurements, which are consistent with a power law dependence of the exclusive J/ψJ/\psi photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.Comment: 25 pages, 3 captioned figures, 3 tables, authors from page 19, published version, figures at http://alice-publications.web.cern.ch/node/455

    Measurement of the production of charm jets tagged with D0^{0} mesons in pp collisions at s\sqrt{s}= 7 TeV

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    The production of charm jets in proton-proton collisions at a center-of-mass energy of s=7\sqrt{s}=7 TeV was measured with the ALICE detector at the CERN Large Hadron Collider. The measurement is based on a data sample corresponding to a total integrated luminosity of 6.236.23 nb1{\rm nb}^{-1}, collected using a minimum-bias trigger. Charm jets are identified by the presence of a D0^0 meson among their constituents. The D0^0 mesons are reconstructed from their hadronic decay D0^0\rightarrowKπ+^{-}\pi^{+}. The D0^0-meson tagged jets are reconstructed using tracks of charged particles (track-based jets) with the anti-kTk_{\mathrm{T}} algorithm in the jet transverse momentum range 5<pT,jetch<305<p_{\rm{T,jet}}^{\mathrm{ch}}<30 GeV/c{\rm GeV/}c and pseudorapidity ηjet<0.5|\eta_{\rm jet}|<0.5. The fraction of charged jets containing a D0^0-meson increases with pT,jetchp_{\rm{T,jet}}^{\rm{ch}} from 0.042±0.004(stat)±0.006(syst)0.042 \pm 0.004\, \mathrm{(stat)} \pm 0.006\, \mathrm{(syst)} to 0.080±0.009(stat)±0.008(syst)0.080 \pm 0.009\, \rm{(stat)} \pm 0.008\, \rm{(syst)}. The distribution of D0^0-meson tagged jets as a function of the jet momentum fraction carried by the D0^0 meson in the direction of the jet axis (zchz_{||}^{\mathrm{ch}}) is reported for two ranges of jet transverse momenta, 5<pT,jetch<155<p_{\rm{T,jet}}^{\rm{ch}}<15 GeV/c{\rm GeV/}c and 15<pT,jetch<3015<p_{\rm{T,jet}}^{\rm{ch}}<30 GeV/c{\rm GeV/}c in the intervals 0.2<zch<1.00.2<z_{||}^{\rm{ch}}<1.0 and 0.4<zch<1.00.4<z_{||}^{\rm{ch}}<1.0, respectively. The data are compared with results from Monte Carlo event generators (PYTHIA 6, PYTHIA 8 and Herwig 7) and with a Next-to-Leading-Order perturbative Quantum Chromodynamics calculation, obtained with the POWHEG method and interfaced with PYTHIA 6 for the generation of the parton shower, fragmentation, hadronisation and underlying event.Comment: 29 pages, 8 captioned figures, 3 tables, authors from page 24, published version, figures at http://alice-publications.web.cern.ch/node/525

    First measurement of Ξc0\Xi_{\rm c}^0 production in pp collisions at s\mathbf{\sqrt{s}} = 7 TeV

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    The production of the charm-strange baryon Ξc0\Xi_{\rm c}^0 is measured for the first time at the LHC via its semileptonic decay into e+Ξνe^+\Xi^-\nu_{\rm e} in pp collisions at s=7\sqrt{s}=7 TeV with the ALICE detector. The transverse momentum (pTp_{\rm T}) differential cross section multiplied by the branching ratio is presented in the interval 1 << pTp_{\rm T} << 8 GeV/cc at mid-rapidity, y|y| << 0.5. The transverse momentum dependence of the Ξc0\Xi_{\rm c}^0 baryon production relative to the D0^0 meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio.Comment: 22 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/412

    Constraining the magnitude of the Chiral Magnetic Effect with Event Shape Engineering in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76$ TeV

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    In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow v2v_2 reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb-Pb collisions at sNN=2.76\sqrt{s_{_{\rm NN}}} =2.76 TeV. The two-particle correlator cos(φαφβ)\langle \cos(\varphi_\alpha - \varphi_\beta) \rangle, calculated for different combinations of charges α\alpha and β\beta, is almost independent of v2v_2 (for a given centrality), while the three-particle correlator cos(φα+φβ2Ψ2)\langle \cos(\varphi_\alpha + \varphi_\beta - 2\Psi_2) \rangle scales almost linearly both with the event v2v_2 and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on v2v_2 points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10-50% centrality interval is found to be 26-33% at 95% confidence level.Comment: 20 pages, 6 captioned figures, 1 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/382
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