Since the first particle accelerator’s construction in 1931, an exponential spread of these machines occurred worldwide, in different kinds of applications. Nowadays, these are mainly used for ...industrial (60%) and medical (35%) purposes and for scientific research (5%). High energy secondary mixed fields produced by the particle beams interaction with matter imply a complex environmental dosimetry and special radiation protection regulations able to guarantee workers and population safety. In the medical field, this aspect is particularly emphasized in hadrontherapy centres, where high energy charged particles such as protons and carbon ions modify environmental doses, with a significant increase in the neutron contribution. This work proposes a technique to identify points of losses of the primary particle beam around an acceleration ring and has been developed within the radiation protection section at the National Centre for Oncological Hadrontherapy situated in Pavia. In the first part, the radiation field produced by protons and carbon ions interactions with structural materials at different energies was investigated. The main instrument of analysis is the Monte Carlo code for particle transport FLUKA, supported by experimental measurements in the treatment room carried out with the rem counter LUPIN, designed for pulsed neutron fields dosimetry. This first step allowed an analysis of both the angular and energetic instrumental response and a comparison of experimental results with simulations. The second part proposes a description of the technique for beam loss positions reconstruction around the acceleration ring at CNAO based on the application of unfolding codes.
Concern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX ...genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus SA, 50 MSSA, 259 MR S. pseudintermedius SP, 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC ≥64 mg/L (n = 27) fusA and fusE were amplified and sequenced.
FA resistance determinants (fusA mutations n = 24, fusB n = 2, fusC n = 36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (≥1 mg/L), although 4 SP isolates had MICs of 0.06 mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n = 2) and smr (n = 5), which were found in SEUK SA, and SP from NUK and U.S.A.
Increased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy.
Asymmetrical
N
,
N
-bis(alkanol)amine aryl esters (FRA77, GDE6, and GDE19) are potent multidrug resistance (MDR) reversers. Their structures loosely remind that of the Ca
2+
antagonist verapamil. ...Therefore, the aim of this study was to investigate their vascular activity in vitro. Their effects on the mechanical activity of fresh and cultured rat aorta rings on Ca
v
1.2 channel current (
I
Ca1.2
) of A7r5 cells and their cytotoxicity on A7r5 and EA.hy926 cells were analyzed. Docking at the rat α
1C
subunit of the Ca
v
1.2 channel was simulated in silico. Compounds tested were cytotoxic at concentrations >1 μM (FRA77, GDE6, GDE19) and >10 μM (verapamil) in EA.hy926 cells, or >10 μM (FRA77, GDE6, GDE19) and at 100 μM (verapamil) in A7r5 cells. In fresh rings, the three compounds partly antagonized phenylephrine and 60 mM K
+
(K60)-induced contraction at concentrations ≥1 and ≥3 μM, respectively. On the contrary, verapamil fully relaxed rings pre-contracted with both agents. In cultured rings, 10 μM GDE6, GDE19, FRA77, and verapamil significantly reduced the contractile response to both phenylephrine and K60. Similarly to verapamil, the three compounds docked at the α
1C
subunit, interacting with the same amino acids residues. FRA77, GDE6, and GDE19 inhibited
I
Ca1.2
with IC
50
values 1 order of magnitude higher than that of verapamil. FRA77-, GDE6-, and GDE19-induced vascular effects occurred at concentrations that are at least 1 order of magnitude higher than those effectively reverting MDR. Though an unambiguous divergence between MDR reverting and vascular activity is of overwhelming importance, these findings consistently contribute to the design and synthesis of novel and potent chemosensitizers.
► Estrogen-like chemicals at μM–mM concentrations have cytotoxic effects on BeWo and HTR-8/SVneo trophoblast cells. ► Estrogen-like chemicals at non-cytotoxic (pM–nM) concentrations alter β-hCG ...secretion in BeWo trophoblast-like cells. ► BeWo cells are a suitable model for studying the effects of low doses of various environmental chemicals on human placenta.
The identification of reproductive toxicants is a major scientific challenge for human health. We investigated the effects of a selected group of environmental polluting chemicals mostly provided with estrogenic activity on the human trophoblast cell lines BeWo and HTR-8/SVneo. Cells were exposed for 24h to various concentrations (from 0.1pM to 1mM) of atrazine (ATR), diethylstilbestrol (DES), para-nonylphenol (p-NP), resveratrol (RES) and 17 β-estradiol (E2) and assayed for cell viability and human beta-Chorionic Gonadotropin (β-hCG) secretion.
Decrease of cell viability as respect to control, vehicle-treated, cultures was obtained for all chemicals in the concentration range of 1μM–1mM in both cell types.
A parallel decrease of β-hCG secretion was observed in BeWo cells, at 1μM–1mM concentrations, with the only exception of ATR which caused an increase at concentrations up to 1mM. β-hCG release was also unexpectedly inhibited by ATR, DES, p-NP and RES at non-toxic (pM–nM) concentrations.
These findings raise concern about the negative, potential effects of various environmental polluting chemicals on pregnancy success and fetal health.
In order to solve the A-body Schrödinger equation both accurately and efficiently for open-shell nuclei, a novel many-body method coined as Bogoliubov many-body perturbation theory (BMBPT) was ...recently formalized and applied at low orders. Based on the breaking of U(1) symmetry associated with particle-number conservation, this perturbation theory must operate under the constraint that the average number of particles is self-consistently adjusted at each perturbative order. The corresponding formalism is presently detailed with the goal to characterize the behaviour of the associated Taylor series. BMBPT is, thus, investigated numerically up to high orders at the price of restricting oneself to a small, i.e. schematic, portion of Fock space. While low-order results only differ by 2−3% from those obtained via a configuration interaction (CI) diagonalization, the series is shown to eventually diverge. The application of a novel resummation method coined as eigenvector continuation further increases the accuracy when built from low-order BMBPT corrections and quickly converges towards the CI result when applied at higher orders. Furthermore, the numerically-costly self-consistent particle number adjustment procedure is shown to be safely bypassed via the use of a computationally cheap a posteriori correction method. Eventually, the present work validates the fact that low order BMBPT calculations based on an a posteriori (average) particle number correction deliver controlled results and demonstrates that they can be optimally complemented by the eigenvector continuation method to provide results with sub-percent accuracy. This approach is, thus, planned to become a workhorse for realistic ab initio calculations of open-shell nuclei in the near future.
•Low-order BMBPT is validated as a cheap workhorse for singly open-shell nuclei.•Eigenvector continuation presents great potential to achieve high-accuracy results.•Particle-number constraint can be bypassed by low-cost a posteriori correction.
The neon isotopic chain displays a rich phenomenology, ranging from clustering in the ground-state of the self-conjugate doubly open-shell stable
20
Ne isotope to the physics of the island of ...inversion around the neutron-rich
30
Ne isotope. This second (i.e. Paper II) of the present series proposes an extensive ab initio study of neon isotopes based on two complementary many-body methods, i.e. the quasi-exact in-medium no-core shell model (IM-NCSM) and the projected generator coordinate method (PGCM) that is ideally suited to capturing strong static correlations associated with shape deformation and fluctuations. Calculations employ a state-of-the-art generation of chiral effective field theory Hamiltonians and evaluate the associated systematic uncertainties. In spite of missing so-called dynamical correlations, which can be added via the multi-reference perturbation theory proposed in the first paper (i.e. Paper I) of the present series
1
, the PGCM is shown to be a suitable method to tackle the low-lying spectroscopy of complex nuclei. Still, describing the physics of the island of inversion constitutes a challenge that seems to require the inclusion of dynamical correlations. This is addressed in the third paper (i.e. Paper III) of the present series
2
.
In spite of missing dynamical correlations, the projected generator coordinate method (PGCM) was recently shown to be a suitable method to tackle the low-lying spectroscopy of complex nuclei. Still, ...describing absolute binding energies and reaching high accuracy eventually requires the inclusion of dynamical correlations on top of the PGCM. In this context, the present work discusses the first realistic results of a novel multi-reference perturbation theory (PGCM-PT) that can do so within a symmetry-conserving scheme for both ground and low-lying excited states. First, proof-of-principle calculations in a small (
e
max
=
4
) model space demonstrate that exact binding energies of closed- (
16
O
) and open-shell (
18
O
,
20
Ne
) nuclei are reproduced within 0.5–
1.5
%
at second order, i.e. through PGCM-PT(2). Moreover, profiting from the pre-processing of the Hamiltonian via multi-reference in-medium similarity renormalization group transformations, PGCM-PT(2) can reach converged values within smaller model spaces than with an unevolved Hamiltonian. Doing so, dynamical correlations captured by PGCM-PT(2) are shown to bring essential corrections to low-lying excitation energies that become too dilated at leading order, i.e., at the strict PGCM level. The present work is laying the foundations for a better understanding of the optimal way to grasp static and dynamical correlations in a consistent fashion, with the aim of accurately describing ground and excited states of complex nuclei via ab initio many-body methods.
PDF
