Theoretical S1 \u2192S0 Absorption Energies of the Anionic Forms of Oxyluciferin by Variational Monte Carlo and Many-Body Green's Function Theory

The structures of three negatively charged forms (anionic keto-1 and enol-1 and dianionic enol-2) of oxyluciferin (OxyLuc), which are the most probable emitters responsible for the firefly bioluminescence, have been fully relaxed at the variational Monte Carlo (VMC) level. Absorption energies of the S1 \u2190 S0 vertical transition have been computed using different levels of theory, such as TDDFT, CC2, and many-body Green\u2019s function theory (MBGFT). The use of MBGFT, by means of the Bethe\u2013Salpeter (BS) formalism, on VMC structures provides results in excellent agreement with the value (2.26(8) eV) obtained by action spectroscopy experiments for the keto-1 form (2.32 eV). To unravel the role of the quality of the optimized ground-state geometry, BS excitation energies have also been computed on CASSCF geometries, inducing a non-negligible blue shift (0.08 and 0.07 eV for keto-1 and enol-1 forms, respectively) with respect to the VMC ones. Structural effects have been analyzed in terms of over- or undercorrelation along the conjugated bonds of OxyLuc by using different methods for the ground-state optimization. The relative stability of the S1 state for the keto-1 and enol-1 forms depends on the method chosen for the excited-state calculation, thus representing a fundamental caveat for any theoretical study on these systems. Finally, Kohn\u2013Sham HOMO and LUMO orbitals of enol-2 are (nearly) bound only when the dianion is embedded into a solvent (water and toluene in the present work); excited-state calculations are therefore meaningful only in the presence of a dielectric medium which localizes the electronic density. The combination of VMC for the ground-state geometry and BS formalism for the absorption spectra clearly outperforms standard TDDFT and quantum chemistry approaches

Wideband dual sphere detector of gravitational waves

We present the concept of a sensitive AND broadband resonant mass gravitational wave detector. A massive sphere is suspended inside a second hollow one. Short, high-finesse Fabry-Perot optical cavities read out the differential displacements of the two spheres as their quadrupole modes are excited. At cryogenic temperatures one approaches the Standard Quantum Limit for broadband operation with reasonable choices for the cavity finesses and the intracavity light power. A molybdenum detector of overall size of 2 m, would reach spectral strain sensitivities of 2x10^-23/Sqrt{Hz} between 1000 Hz and 3000 Hz.Comment: 4 pages, 3 figures. Changed content. To appear in Phys. Rev. Let

Gravitational-Wave Stochastic Background Detection with Resonant-Mass Detectors

In this paper we discuss how the standard optimal Wiener filter theory can be applied, within a linear approximation, to the detection of an isotropic stochastic gravitational-wave background with two or more detectors. We apply then the method to the AURIGA-NAUTILUS pair of ultra low temperature bar detectors, near to operate in coincidence in Italy, obtaining an estimate for the sensitivity to the background spectral density of $\simeq 10^{-49}\ Hz^{-1}$, that converts to an energy density per unit logarithmic frequency of$\simeq 8\times10^{-5}\times\rho_c$with$\rho_c\simeq1.9 \times 10^{-26}\ kg/m^3$the closure density of the Universe. We also show that by adding the VIRGO interferometric detector under construction in Italy to the array, and by properly re- orienting the detectors, one can reach a sensitivity of$\simeq 6 \times10^{-5}\times\rho_c$. We then calculate that the pair formed by VIRGO and one large mass spherical detector properly located in one of the nearby available sites in Italy can reah a sensitivity of$\simeq 2\times10^{-5}\times \rho_c$while a pair of such spherical detectors at the same sites of AURIGA and NAUTILUS can achieve sensitivities of$\simeq 2 \times10^{-6}\rho_c$.Comment: 32 pages, postscript file, also available at http://axln01.lnl.infn.it/reports/stoch.htm

Path-breaking directions of nanotechnology-based chemotherapy and molecular cancer therapy

WP 01/14; A fundamental question is how to detect likely successful anticancer treatments based on nanotechnology. We confront this question here by analyzing the trajectories of nanotechnologies applied to path-breaking cancer treatments, which endeavour to pinpoint ground-breaking and fruitful directions in nanomedicine. Results tend to show two main technological waves of cancer treatments by nanotechnology applications. The early technological wave in the early 2000s was embodied in some types of chemotherapy agents with a broad spectrum, while after 2006, the second technological wave appeared with new nano-technological applications in both chemotherapy agents and molecular target therapy. The present study shows new directions of nanotechnology-based chemotherapy and -molecular cancer therapy in new treatments for breast, lung, brain and colon cancers. A main finding of this study is the recognition that, since the late 2000s, the sharp increase of several technological trajectories of nanotechnologies and anticancer drugs seems to be driven by high rates of mortality of some types of cancers (e.g. pancreatic and brain ones) in order to find more effectiveness anticancer therapies that increase the survival of patients. The study here also shows that worldwide leader countries in these vital research fields and in particular the specialization of some countries in applications of nanotechnology to treat specific cancer (e.g. Switzerland in prostate cancer, Japan in colon, China in ovarian and Greece in pancreatic cancer). These ground-breaking technological trajectories are paving new directions in biomedicine and generating a revolution in clinical practice that may lead to more effective anticancer treatments in a not-too-distant futur

The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival

Background: The role of the CD70-specific antibody and the mechanisms by which it extends transplant survival are not known. Methods: Fully major histocompatibility complex-mismatched heterotopic heart transplantation (BALB/c to C57BL/6) was performed. Treated mice received intraperitoneal injections of wild-type (WT) CD70-specific antibody (FR70) or IgG1 or IgG2a chimeric antibodies on days 0, 2, 4, and 6 posttransplantation. Results: WT FR70 antibody significantly extended heart transplant survival to 19 days compared with untreated mice (median survival time [MST]=10 days). Graft survival using the nondepleting IgG1 antibody was significantly shorter (MST=14 days), whereas the survival using depleting IgG2a antibody (MST=18) was similar to that using WT FR70. The FR70 and IgG2a antibodies demonstrated a greater efficiency of fixing mouse complement over the IgG1 variant in vitro. CD4 and CD8 T-cell graft infiltration was reduced with treatment; however, this was most pronounced with WT FR70 and IgG2a antibody therapy compared with the IgG1 chimeric variant. Circulating donor-specific IgG alloantibodies were initially reduced with WT FR70 treatment (day 8 posttransplantation) but increased at days 15 and 20 posttransplantation to the level detected in untreated controls. Conclusion: We conclude that WT (FR70) and the IgG2a depleting variant of CD70-specific antibody reduce graft infiltrating CD4 and CD8 T cells, transiently reduce serum alloantibody levels, and extend graft survival. In contrast, the nondepleting IgG1 variant of this antibody showed lower efficacy. These data suggest that a depleting mechanism of action and not merely costimulation blockade plays a substantial role in the therapeutic effects of CD70-specific antibody