Robot-assisted intermanual transfer of handwriting skills

n/

Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines

BACKGROUND: Thymidylate synthase (TS), one of the key enzymes for thymidine synthesis, is a target of pemetrexed (PEM), a key agent for the systemic therapy of malignant pleural mesothelioma (MPM) and its overexpression has been correlated to PEM-resistance. In MPM, experimental data report activation of the c-SRC tyrosine kinase suggesting it as a potential target to be further investigated. RESULTS: MPM cell lines showed different sensitivity, being MSTO the most and REN the least sensitive to PEM. REN cells showed high levels of both TS and SRC: dasatinib inhibited SRC activation and suppressed TS protein expression, starting from 100 nM dose, blocking the PEM-induced up regulation of TS protein levels. Dasatinib treatment impaired cells migration, and both sequential and co-administration with PEM significantly increased apoptosis. Dasatinib pretreatment improved sensitivity to PEM, downregulated TS promoter activity and, in association with PEM, modulated the downstream PI3K-Akt-mTOR signaling. CELL LINES AND METHODS: In three MPM cell lines (MPP89, REN and MSTO), the effects of c-SRC inhibition, in correlation with TS expression and PEM sensitivity, were evaluated. PEM and dasatinib, a SRC inhibitor, were administered as single agents, in combination or sequentially. Cell viability, apoptosis and migration, as well as TS expression and SRC activation have been assessed. CONCLUSIONS: These data indicate that dasatinib sensitizes mesothelioma cells to PEM through TS down-regulation

Simulations and measurements of cleaning with 100 MJ beams in the LHC

The CERN Large Hadron Collider is routinely storing proton beam intensities of more than 100 MJ, which puts extraordinary demands on the control of beam losses to avoid quenches of the superconducting magnets. Therefore, a detailed understanding of the LHC beam cleaning is required. We present tracking and shower simulations of the LHC's multi-stage collimation system and compare with measured beam losses, which allow us to conclude on the predictive power of the simulations.Asian Committee for Future Accelerators (ACFA),American Physical Society Division of Physics of Beams (APS-DPB),Chinese Academy of Sciences (CAS),European Physical Society Accelerator Group (EPS-AG)peer-reviewe

Simulations and measurements of beam loss patterns at the CERN Large Hadron Collider

The CERN Large Hadron Collider (LHC) is designed to collide proton beams of unprecedented energy, in order to extend the frontiers of high-energy particle physics. During the first very successful running period in 2010-2013, the LHC was routinely storing protons at 3.5-4 TeV with a total beam energy of up to 146 MJ, and even higher stored energies are foreseen in the future. This puts extraordinary demands on the control of beam losses. An uncontrolled loss of even a tiny fraction of the beam could cause a superconducting magnet to undergo a transition into a normal-conducting state, or in the worst case cause material damage. Hence a multistage collimation system has been installed in order to safely intercept high-amplitude beam protons before they are lost elsewhere. To guarantee adequate protection from the collimators, a detailed theoretical understanding is needed. This article presents results of numerical simulations of the distribution of beam losses around the LHC that have leaked out of the collimation system. The studies include tracking of protons through the fields of more than 5000 magnets in the 27 km LHC ring over hundreds of revolutions, and Monte Carlo simulations of particle-matter interactions both in collimators and machine elements being hit by escaping particles. The simulation results agree typically within a factor 2 with measurements of beam loss distributions from the previous LHC run. Considering the complex simulation, which must account for a very large number of unknown imperfections, and in view of the total losses around the ring spanning over 7 orders of magnitude, we consider this an excellent agreement. Our results give confidence in the simulation tools, which are used also for the design of future accelerators.peer-reviewe

Planck 2018 results. XII. Galactic astrophysics using polarized dust emission

We present 353 GHz full-sky maps of the polarization fraction p, angle \u3c8, and dispersion of angles S of Galactic dust thermal emission produced from the 2018 release of Planck data. We confirm that the mean and maximum of p decrease with increasing NH. The uncertainty on the maximum polarization fraction, pmax=22.0% at 80 arcmin resolution, is dominated by the uncertainty on the zero level in total intensity. The observed inverse behaviour between p and S is interpreted with models of the polarized sky that include effects from only the topology of the turbulent Galactic magnetic field. Thus, the statistical properties of p, \u3c8, and S mostly reflect the structure of the magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map S 7p, looking for residual trends. While p decreases by a factor of 3--4 between NH=1020 cm 122 and NH=2 71022 cm 122, S 7p decreases by only about 25%, a systematic trend observed in both the diffuse ISM and molecular clouds. Second, we find no systematic trend of S 7p with the dust temperature, even though in the diffuse ISM lines of sight with high p and low S tend to have colder dust. We also compare Planck data with starlight polarization in the visible at high latitudes. The agreement in polarization angles is remarkable. Two polarization emission-to-extinction ratios that characterize dust optical properties depend only weakly on NH and converge towards the values previously determined for translucent lines of sight. We determine an upper limit for the polarization fraction in extinction of 13%, compatible with the pmax observed in emission. These results provide strong constraints for models of Galactic dust in diffuse gas

Planck 2018 results. XII. Galactic astrophysics using polarized dust emission

We present 353 GHz full-sky maps of the polarization fraction $p$, angle $\psi$, and dispersion of angles $S$ of Galactic dust thermal emission produced from the 2018 release of Planck data. We confirm that the mean and maximum of $p$ decrease with increasing $N_H$. The uncertainty on the maximum polarization fraction, $p_\mathrm{max}=22.0$% at 80 arcmin resolution, is dominated by the uncertainty on the zero level in total intensity. The observed inverse behaviour between $p$ and $S$ is interpreted with models of the polarized sky that include effects from only the topology of the turbulent Galactic magnetic field. Thus, the statistical properties of $p$, $\psi$, and $S$ mostly reflect the structure of the magnetic field. Nevertheless, we search for potential signatures of varying grain alignment and dust properties. First, we analyse the product map $S \times p$, looking for residual trends. While $p$ decreases by a factor of 3--4 between $N_H=10^{20}$ cm$^{-2}$ and $N_H=2\times 10^{22}$ cm$^{-2}$, $S \times p$ decreases by only about 25%, a systematic trend observed in both the diffuse ISM and molecular clouds. Second, we find no systematic trend of $S \times p$ with the dust temperature, even though in the diffuse ISM lines of sight with high $p$ and low $S$ tend to have colder dust. We also compare Planck data with starlight polarization in the visible at high latitudes. The agreement in polarization angles is remarkable. Two polarization emission-to-extinction ratios that characterize dust optical properties depend only weakly on $N_H$ and converge towards the values previously determined for translucent lines of sight. We determine an upper limit for the polarization fraction in extinction of 13%, compatible with the $p_\mathrm{max}$ observed in emission. These results provide strong constraints for models of Galactic dust in diffuse gas

Collimation for the LHC high intensity beams

The unprecedented design intensities of the LHC require several important advances in beam collimation. With its more than 100 collimators, acting on various planes and beams, the LHC collimation system is the biggest and most performing such system ever designed and constructed. The solution for LHC collimation is explained, the technical components are introduced and the initial performance is presented. Residual beam leakage from the system is analysed. Measurements and simulations are presented which show that collimation efficiencies of better than 99.97 % have been measured with the 3.5 TeV proton beams of the LHC, in excellent agreement with expectations.peer-reviewe

Antiphospholipid syndrome and the heart: A case series and literature review

Antiphospholipid syndrome is a rare autoimmune disease characterised by a high tendency of developing thrombotic events. It is diagnosed in the presence of specific laboratory criteria (positivity for lupus anticoagulant, and the presence of anticardiolipin and a\u3b22GPI antibodies) and clinical criteria such as thrombosis in any district (arterial or venous) and pregnancy morbidity. Being a multisystem disease, heart is commonly affected by direct (autoimmune mediated action) or indirect (thrombosis) pathological mechanisms. Heart valve lesions are the most frequent manifestations; however, the haemodynamic significance is quite uncommon but when it occurs it may require surgery that further complicates the picture due to the high risk of thrombosis. Coronary arteries and myocardium are also affected leading to ischaemic heart disease and left ventricular dysfunction. Other findings include chronic thromboembolic pulmonary hypertension and accelerated atherosclerosis. The consequences of heart involvement may be significant in overt disease. The treatment of cardiac complications is challenging and requires an in depth knowledge of the disease

What have we learned about antiphospholipid syndrome from patients and antiphospholipid carrier cohorts?

Venous or arterial thrombosis or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL) define the antiphospholipid syndrome (APS). In terms of accepted APS criteria, aPL are detected by one coagulation test (lupus anticoagulant; LAC) and two immunoassays (anticardiolipin antibodies and anti-beta(2)-glycoptrotein I antibodies). In patients with APS, a single positive test carries a much lower risk of thrombosis recurrence or new pregnancy loss than does multiple (or triple) positivity. The same holds true for aPL carriers, namely subjects with laboratory tests but without clinical criteria for APS. Thus, very different risk categories exist among patients with APS as well as in carriers of aPL. Triple positivity apparently identifies the pathogenic autoantibody (antidomain I-II of beta(2)-glycoptrotein I); it is in this category of patients that trials on new therapeutic strategies should focus