Principles of wide bandwidth acoustic detectors and the single-mass DUAL detector

We apply the standard theory of the elastic body to obtain a set of equations describing the behavior of an acoustic Gravitational Wave detector, fully taking into account the 3-dimensional properties of the mass, the readout and the signal. We show that the advantages given by a Dual detector made by two nested oscillators can also be obtained by monitoring two different acoustic modes of the same oscillator, thus easing the detector realization. We apply these concepts and by means of an optimization process we derive the main figures of such a single-mass Dual detector designed specifically for the frequency interval 2-5kHz. Finally we calculate the SQL sensitivity of this detector.Comment: 29 pages, 10 figure

PO-035 LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitor

Introduction Lung Cancer is the first cause of cancer-related death in the world. The alterations in KRAS oncogene are very frequent (25%), but, unfortunately, this protein is at present undruggable. KRAS mutations determine over-activation of important pathways of growth and proliferation (PI3K-AKT-mTOR and MAPK). KRAS-mutated tumours are also frequently co-mutated in LKB1 (50%), an important regulator of metabolic homeostasis and oxidative stress in the cells. LKB1 modulates catabolic processes through AMPK-mediated mTOR inhibition. Thereafter, the inactivation of LKB1 causes in KRAS mutated-tumours further activation of PI3K-AKT-mTOR and MAPK pathways, making them particularly aggressive. The possibility to specifically target tumours with both KRAS and LKB1 alterations represent an important medical need. Material and methods We generated from the NSCLC cell line NCI-H1299 clones over-expressing KRAS WT or KRAS G12C forms. These clones have been subsequently modified through CRISPR-CAS9 system to obtain deletions in LKB1 gene. We successfully generated isogenic cells differing only for the status of KRAS and LKB1 (KRASwt/LKB1wt, KRASmut/LKB1wt, KRASwt/LKB1mut, KRASmut/LKB1mut). These clones were treated with a panel of inhibitors of MAPK and PI3K pathways. Viability was evaluated with MTS assay. Molecular characterizations were performed by western blot analysis. In vivo antitumor activity was determined after subcutaneous injection of NSCLC cells in immunodeficient mice. Results and discussions Using the isogenic system generated we tested the activity of several inhibitors of MAPK and PI3K pathways. The results highlighted a strong response of the clones with deletion in LKB1 to ERK inhibitor, independently from the KRAS status. These results were confirmed 'in vivo', where tumours with LKB1 deletion showed a significant sensitivity to ERK inhibitor, compared to LKB1 WT tumours. At molecular level we tested the activation of proteins related to MAPK and PI3K pathway such as p70, S6, 4-EBP1, ERK. The results showed that the response to ERK inhibitor was mainly due to mTOR signalling inhibition. Conclusion The results obtained highlight a possible strategy to target NSCLC with KRAS-LKB1 co-mutations, that, at moment are those with a worse prognosis. The sensitivity to ERK inhibitor is remarkable, also in presence of KRAS WT, therefore this strategy could be applied to all LKB1-mutated lung tumours, that represent 30% of all NSCLC. These studies are being confirmed in other NSCLC backgrounds and mouse models

Efficient characterisation of large deviations using population dynamics

We consider population dynamics as implemented by the cloning algorithm for analysis of large deviations of time-averaged quantities. We use the simple symmetric exclusion process with periodic boundary conditions as a prototypical example and investigate the convergence of the results with respect to the algorithmic parameters, focussing on the dynamical phase transition between homogeneous and inhomogeneous states, where convergence is relatively difficult to achieve. We discuss how the performance of the algorithm can be optimised, and how it can be efficiently exploited on parallel computing platforms

Dc superconducting quantum interference device amplifier for gravitational wave detectors with a true noise temperature of 16 μK

We report on the noise characterization of a two-stage dc superconducting quantum interference device (SQUID) amplifier developed for resonant gravitational wave detectors. The back action noise is estimated by coupling the SQUID to an electrical resonator at 1.6 kHz with Q=1.1×106. From measurements of back action and additive SQUID noise, performed in the temperature range 1.5–4.2 K, an upper limit is set on the noise temperature Tn of the device at the resonator frequency. The best value obtained at 1.5 K is Tn⩽16 μK and corresponds to 200 resonator quanta. The thermal component of the noise temperature is found in reasonable agreement with the predicted value

Modelling nonequilibrium macroscopic oscillators of interest to experimentalists

Recent developments in experimental Gravitational Waves (GW) detection have led to the emergence of concerns regarding the inconsistency of treating the appa-rati as equilibrium systems. Nonequilibrium considerations surface, for example, in examining the electronic feedback machinery that is used to damp and to sta-bilize GW oscillator-bar detectors, or when considering temperature gradients produced by high-powered lasers used in interferometric GWdetectors. Either way, the experimental apparatus often consists of an oscillator with a very high quality factor, subjected to some power supply, and capableof extraordinary sensitivity in length displacement. Two theoretical paradigms (with their advan-tages and disadvantages) are presented: one in which the oscillator is described by an ad hoc Langevin equation with memory, and one in which it is modelled by a deterministic one-dimensional chain of anharmonic oscillators. Within both, it is seen that GW experiments suggest entirely novel problems to theorist

Low Noise Opto-Electro-Mechanical Modulator for RF-to-Optical Transduction in Quantum Communications

In this work, we present an Opto-Electro-Mechanical Modulator (OEMM) for RF-to-optical transduction realized via an ultra-coherent nanomembrane resonator capacitively coupled to an rf injection circuit made of a microfabricated read-out able to improve the electro-optomechanical interaction. This device configuration can be embedded in a Fabry-Perot cavity for electromagnetic cooling of the LC circuit in a dilution refrigerator exploiting the opto-electro-mechanical interaction. To this aim, an optically measured steady-state frequency shift of 380 Hz was seen with a polarization voltage of 30 V and a $Q$-factor of the assembled device above $10^6$ at room temperature. The rf-sputtered titanium nitride layer can be made superconductive to develop efficient quantum~transducers.Comment: 14 pages, 8 figure

Nonequilibrium issues in macroscopic experiments

Gravitational wave ( G W) detectors are macroscopic instruments with displacement sensitivity approaching the limit set by the uncertainty principle. To this end, reducing the thermal noise down to negligible levels is often a major challenge to the experimentalists. Moreover , making a detect or with noise of pure stationary Gaussian statistics has proven to be as difficult as making a very sensitive one, these two requirements often being contrasting. From the thermodynamic viewpoint , G W experiments are usually modeled as equilibrium systems, but it is doubtful that this description is justified. We discuss the potential impact of non-equilibrium statistics on the performance of G W detectors. We also outline the research plan of the RareNoise project , which addresses this issue, and show so me experimental results on non-equilibrium macroscopic oscillators

Dual detectors of gravitational waves

In a "Dual" gravitational wave (GW) detector a wide band sensitivity is obtained by measuring the differential displacement, driven by the GW, of the facing surfaces of two nested massive bodies mechanically resonating at different frequencies. A "selective readout" scheme, capable of specifically selecting the signal contributed by the vibrational modes sensitive to the gravitational waves, could then reduce the thermal noise contribution from the not sensitive modes. In a dual detector the sensitivity improvement in the displacement transduction could be pursued by means of mechanical amplification systems. This solution is innovative for the resonant GW detectors and we report about preliminary theoretical and experimental study