Q-Value and Half-Lives for the Double-Beta-Decay Nuclide 110Pd

The 110Pd double-beta decay Q-value was measured with the Penning-trap mass spectrometer ISOLTRAP to be Q = 2017.85(64) keV. This value shifted by 14 keV compared to the literature value and is 17 times more precise, resulting in new phase-space factors for the two-neutrino and neutrinoless decay modes. In addition a new set of the relevant matrix elements has been calculated. The expected half-life of the two-neutrino mode was reevaluated as 1.5(6) E20 yr. With its high natural abundance, the new results reveal 110Pd to be an excellent candidate for double-beta decay studies

Probing the N = 32 shell closure below the magic proton number Z = 20: Mass measurements of the exotic isotopes 52,53K

The recently confirmed neutron-shell closure at N = 32 has been investigated for the first time below the magic proton number Z = 20 with mass measurements of the exotic isotopes 52,53K, the latter being the shortest-lived nuclide investigated at the online mass spectrometer ISOLTRAP. The resulting two-neutron separation energies reveal a 3 MeV shell gap at N = 32, slightly lower than for 52Ca, highlighting the doubly-magic nature of this nuclide. Skyrme-Hartree-Fock-Boguliubov and ab initio Gorkov-Green function calculations are challenged by the new measurements but reproduce qualitatively the observed shell effect.Comment: 5 pages, 5 figure

Pharmacokinetic Modeling of an Induction Regimen for In Vivo Combined Testing of Novel Drugs against Pediatric Acute Lymphoblastic Leukemia Xenografts

Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL), or for re-induction post relapse, use a combination of vincristine (VCR), a glucocorticoid, and l-asparaginase (ASP) with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX) and ASP (VXL) against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL

Cetuximab Augments Cytotoxicity with Poly (ADP-Ribose) Polymerase Inhibition in Head and Neck Cancer

Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of head and neck cancers and confers increased resistance and inferior survival rates. Despite targeted agents against EGFR, such as cetuximab (C225), almost half of treated patients fail this therapy, necessitating novel therapeutic strategies. Poly (ADP-Ribose) polymerase (PARP) inhibitors (PARPi) have gained recent attention due to their unique selectivity in killing tumors with defective DNA repair. In this study, we demonstrate that C225 enhances cytotoxicity with the PARPi ABT-888 in UM-SCC1, UM-SCC6, and FaDu head and neck cancer cells. The mechanism of increased susceptibility to C225 and PARPi involves C225-mediated reduction of non-homologous end-joining (NHEJ)- and homologous recombination (HR)-mediated DNA double strand break (DSB) repair, the subsequent persistence of DNA damage, and activation of the intrinsic apoptotic pathway. By generating a DSB repair deficiency, C225 can render head and neck tumor cells susceptible to PARP inhibition. The combination of C225 and the PARPi ABT-888 can thus be an innovative treatment strategy to potentially improve outcomes in head and neck cancer patients. Furthermore, this strategy may also be feasible for other EGFR overexpressing tumors, including lung and brain cancers

Charge radii and electromagnetic moments of 195-211At

Hyperfine-structure parameters and isotope shifts of At195-211 have been measured for the first time at CERN-ISOLDE, using the in-source resonance-ionization spectroscopy method. The hyperfine structures of isotopes were recorded using a triad of experimental techniques for monitoring the photo-ion current. The Multi-Reflection Time-of-Flight Mass Spectrometer, in connection with a high-resolution electron multiplier, was used as an ion-counting setup for isotopes that either were affected by strong isobaric contamination or possessed a long half-life; the ISOLDE Faraday cups were used for cases with high-intensity beams; and the Windmill decay station was used for short-lived, predominantly α-decaying nuclei. The electromagnetic moments and changes in the mean-square charge radii of the astatine nuclei have been extracted from the measured hyperfine-structure constants and isotope shifts. This was only made possible by dedicated state-of-the-art large-scale atomic computations of the electronic factors and the specific mass shift of atomic transitions in astatine that are needed for these extractions. By comparison with systematics, it was possible to assess the reliability of the results of these calculations and their ascribed uncertainties. A strong deviation in the ground-state mean-square charge radii of the lightest astatine isotopes, from the trend of the (spherical) lead isotopes, is interpreted as the result of an onset of deformation. This behavior bears a resemblance to the deviation observed in the isotonic polonium isotopes. Cases for shape coexistence have been identified in At197,199, for which a significant difference in the charge radii for ground (9/2-) and isomeric (1/2+) states has been observed

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Inverse odd-even staggering in nuclear charge radii and possible octupole collectivity in $^217,218,219At revealed by in-source laser spectroscopy

International audienceHyperfine-structure parameters and isotope shifts for the 795-nm atomic transitions in $^{217,218,219}$At have been measured at CERN-ISOLDE, using the in-source resonance-ionization spectroscopy technique. Magnetic dipole and electric quadrupole moments, and changes in the nuclear mean-square charge radii, have been deduced. A large inverse odd-even staggering in radii, which may be associated with the presence of octupole collectivity, has been observed. Namely, the radius of the odd-odd isotope $^{218}$At has been found to be larger than the average of its even-$N$ neighbors, $^{217,219}$At. The discrepancy between the additivity-rule prediction and experimental data for the magnetic moment of $^{218}$At also supports the possible presence of octupole collectivity in the considered nuclei

The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years