High-spectral-purity laser system for the AURIGA detector optical readout

We describe a low-frequency-noise laser system conceived for the readout of small mechanical vibrations. The system consists of a Nd:YAG source stabilized to a high-finesse Fabry–Perot cavity and achieves the best performance in the range 1–10 kHz with a minimum residual noise of 4×10-3 Hz/Hz. We perform an extended characterization of the frequency stability by means of an independent optical cavity and we also measure the residual fluctuations after transmission through an optical fiber. Our apparatus is optimized for use in an optical readout for the gravitational wave detector AURIGA, where a laser system with the characteristics reported here will allow an improvement of one order of magnitude in the detector sensitivity

Neutron Star Radius-to-mass Ratio from Partial Accretion Disc Occultation as Measured through Fe Kα\alpha Line Profiles

We present a new method to measure the radius-to-mass ratio (R/M) of weakly magnetic, disc-accreting neutron stars by exploiting the occultation of parts of the inner disc by the star itself. This occultation imprints characteristic features on the X-ray line profile that are unique and are expected to be present in low mass X-ray binary systems seen under inclinations higher than ~65 degrees. We analyse a NuSTAR observation of a good candidate system, 4U 1636-53, and find that X-ray spectra from current instrumentation are unlikely to single out the occultation features owing to insufficient signal-to-noise. Based on an extensive set of simulations we show that large-area X-ray detectors of the future generation could measure R/M to ~2{\div}3% precision over a range of inclinations. Such is the precision in radius determination required to derive tight constraints on the equation of state of ultradense matter and it represents the goal that other methods too aim to achieve in the future.Comment: 17 pages, 8 figures; this is a pre-print edition of an article that has been accepted for publication in the Astrophysical Journa

A folded Fabry-Perot cavity for optical sensing in gravitational wave detectors

Abstract The sensitivity of standard optical schemes for the readout of weak vibrations is limited thermal and radiation pressure fluctuations induced by the small interrogation area. We propose and analyze an optical configuration allowing to overcome this problem and optimize the sensitivity of the new generation of massive gravitational wave detectors

Invasive Candida infection: epidemiology, clinical and therapeutic aspects of an evolving disease and the role of rezafungin

Introduction: Invasive Candida Infections (ICIs) have undergone a series of significant epidemiological, pathophysiological, and clinical changes during the last decades, with a shift toward non-albicans species, an increase in the rate of exogenous infections and clinical manifestations ranging from candidemia to an array of highly invasive and life-threatening clinical syndromes. The long-acting echinocandin rezafungin exhibits potent in-vitro activity against most wild-type and azole-resistant Candida spp. including C. auris. Areas covered: The following topics regarding candidemia only and ICIs were reviewed and addressed: i) pathogenesis; ii) epidemiology and temporal evolution of Candida species; iii) clinical approach; iv) potential role of the novel long-acting rezafungin in the treatment of ICIs. Expert opinion: Authors' expert opinion focused on considering the potential role of rezafungin in the evolving context of ICIs. Rezafungin, which combines a potent in-vitro activity against Candida species, including azole-resistant strains and C. auris, with a low likelihood of drug-drug interactions and a good safety profile, may revolutionize the treatment of candidemia/ICI. Indeed, it may shorten the length of hospital stays when clinical conditions allow and extend outpatient access to treatment of invasive candidiasis, especially when prolonged treatment duration is expected

Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells

The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors

Prediction of body composition in anorexia nervosa: Results from a retrospective study

Summary Background & aims The assessment of body composition is crucial in evaluating nutritional status in female subjects with anorexia nervosa (AN) and improving their clinical management. The aim of this retrospective study was to assess the accuracy of selected BIA (bioimpedance analysis) equations for fat-free mass (FFM) in female AN subjects and to formulate a specific equation for these subjects. Methods Eighty-two restrictive female AN subjects (age 20.5 ± 3.7 yrs, BMI 15.7 ± 1.7 kg/m 2 ) were studied. Body composition was determined with dual-energy X-ray absorptiometry (DXA) and estimated by BIA using five different equations. Linear correlation analysis was carried out to evaluate the association of FFM with selected variables. Multiple regression analysis was used to formulate specific equations to predict FFM in AN. Results All predictive equations underestimated FFM at the population level with a bias from −5.6 to −11.7%, while the percentage of accurate predictions varied from 12.2% to 35.4%. More interestingly, multiple regression analysis clearly indicates that, in addition to weight, ZI 100 or RI also emerged as independent predictors of DXA-derived FFM, increasing the prediction power of the equation well above that observed with anthropometric characteristics only. Conclusions This study shows that the selected predictive BIA equations considered exhibit an insufficient accuracy at the population and the individual level. Predictive formulas based on body weight plus BIA parameters such as RI and ZI 100 offer a rather accurate prediction of FFM (with high R squared)

An optical readout scheme for advanced acoustic GW detectors

We have recently proposed a large reading area, optical readout scheme for advanced acoustic gravitational wave (GW) detectors. In this work we focus the analysis on a dual-cylinder detector. A specific configuration is designed and the expected performance is calculated

ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors

Background: ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which provides metabolic intermediates to sustain cell proliferation. The aim of our study is to elucidate the role of ATM in the regulation of glucose metabolism in oncogene-driven cancer cells and to test whether ATM may be a suitable target for anticancer therapy. Methods: Two oncogene-driven NSCLC cell lines, namely H1975 and H1993 cells, were treated with ATM inhibitor, KU55933, alone or in combination with oncogene driver inhibitors, WZ4002 or crizotinib. Key glycolytic enzymes, mitochondrial complex subunits (OXPHOS), cyclin D1, and apoptotic markers were analyzed by Western blotting. Drug-induced toxicity was assessed by MTS assay using stand-alone or combined treatment with KU55933 and driver inhibitors. Glucose consumption, pyruvate, citrate, and succinate levels were also analyzed in response to KU55933 treatment. Both cell lines were transfected with ATM-targeted siRNA or non-targeting siRNA and then exposed to treatment with driver inhibitors. Results: ATM inhibition deregulates and inhibits glucose metabolism by reducing HKII, p-PKM2Tyr105, p-PKM2Ser37, E1α subunit of pyruvate dehydrogenase complex, and all subunits of mitochondrial complexes except ATP synthase. Accordingly, glucose uptake and pyruvate concentrations were reduced in response to ATM inhibition, whereas citrate and succinate levels were increased in both cell lines indicating the supply of alternative metabolic substrates. Silencing of ATM resulted in similar changes in glycolytic cascade and OXPHOS levels. Furthermore, the driver inhibitors amplified the effects of ATM downregulation on glucose metabolism, and the combined treatment with ATM inhibitors enhanced the cytotoxic effect of driver inhibitors alone by increasing the apoptotic response. Conclusions: Inhibition of ATM reduced both glycolytic enzymes and OXPHOS levels in oncogene-driven cancer cells and enhanced apoptosis induced by driver inhibitors thus highlighting the possibility to use ATM and the driver inhibitors in combined regimens of anticancer therapy in vivo

Comb-assisted cavity ring-down spectroscopy of a buffer-gas-cooled molecular beam

We demonstrate continuous-wave cavity ring-down spectroscopy of a partially hydrodynamic molecular beam emerging from a buffer-gas-cooling source. Specifically, the (ν1 + ν3) vibrational overtone band of acetylene (C2H2) around 1.5 μm is accessed using a narrow-linewidth diode laser stabilized against a GPS-disciplined rubidium clock via an optical frequency comb synthesizer. As an example, the absolute frequency of the R(1) component is measured with a fractional accuracy of ∼1 × 10(-9). Our approach represents the first step towards the extension of more sophisticated cavity-enhanced interrogation schemes, including saturated absorption cavity ring-down or two-photon excitation, to buffer-gas-cooled molecular beams