555 research outputs found
Biochemodynamic features of metal ions bound by micro- and nano-plastics in aquatic media
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
Screening for subclinical synovial proliferation in haemophilia: A systematic review and meta-analysis comparing physical examination and ultrasound
Introduction: Ultrasound is increasingly used as addition to physical examination for detection of subclinical joint changes in haemophilia. However, the added value of ultrasound to physical examination for detecting synovial proliferation is not fully established. Aim: To determine the diagnostic accuracy of swelling at physical examination for ultrasound-detected synovial proliferation in haemophilia. Methods: PubMed and EMBASE were searched up to 2 August 2022. Studies reporting original data on occurrence of swelling at physical examination and synovial proliferation on ultrasound of index joints in persons with haemophilia were included. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Diagnostic accuracy parameters of swelling at physical examination for ultrasound-detected synovial proliferation were determined. Summary sensitivity and specificity were calculated using a bivariate random-effects model. Results: Fifteen studies reporting on swelling at physical examination and synovial proliferation on ultrasound in 2890 joints of 627 patients were included. Prevalence of subclinical synovial proliferation ranged between 0% and 55%. Sensitivity of swelling was low [summary estimate.34; 95% confidence interval (CI).24-.46], while specificity was high (summary estimate.97; CI.92-.99). Predictive values varied widely due to inter-study differences in prevalence of synovial proliferation. Conclusion: Joint swelling has low sensitivity for presence of ultrasound-detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. Consequently, ultrasound screening may generate important information on synovial changes which would otherwise remain undetected
Sensitizing thermochemotherapy with a PARP1-inhibitor
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
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
First measurement of production in pp collisions at = 7 TeV
The production of the charm-strange baryon is measured for
the first time at the LHC via its semileptonic decay into e
in pp collisions at TeV with the ALICE detector. The transverse
momentum () differential cross section multiplied by the branching
ratio is presented in the interval 1 8 GeV/ at
mid-rapidity, 0.5. The transverse momentum dependence of the
baryon production relative to the D 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 = 2.76$ TeV
In ultrarelativistic heavy-ion collisions, the event-by-event variation of
the elliptic flow 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 TeV. The
two-particle correlator ,
calculated for different combinations of charges and , is
almost independent of (for a given centrality), while the three-particle
correlator
scales almost linearly both with the event 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
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
Energy dependence of exclusive photoproduction off protons in ultra-peripheral p-Pb collisions at = 5.02 TeV
The ALICE Collaboration has measured the energy dependence of exclusive
photoproduction of vector mesons off proton targets in
ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair
TeV. The ee and decay channels
are used to measure the cross section as a function of the rapidity of the
in the range , corresponding to an energy in the
p centre-of-mass in the interval GeV.
The measurements, which are consistent with a power law dependence of the
exclusive 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 D mesons in pp collisions at = 7 TeV
The production of charm jets in proton-proton collisions at a center-of-mass
energy of 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 , collected using a
minimum-bias trigger. Charm jets are identified by the presence of a D
meson among their constituents. The D mesons are reconstructed from their
hadronic decay DK. The D-meson tagged jets are
reconstructed using tracks of charged particles (track-based jets) with the
anti- algorithm in the jet transverse momentum range
and pseudorapidity
. The fraction of charged jets containing a D-meson
increases with from to . The distribution of D-meson tagged jets as a
function of the jet momentum fraction carried by the D meson in the
direction of the jet axis () is reported for two ranges
of jet transverse momenta, and
in the intervals
and , 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
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