Critical Temperature tuning of Ti/TiN multilayer films suitable for low temperature detectors

We present our current progress on the design and test of Ti/TiN Multilayer for use in Kinetic Inductance Detectors (KIDs). Sensors based on sub-stoichiometric TiN film are commonly used in several applications. However, it is difficult to control the targeted critical temperature $T_C$, to maintain precise control of the nitrogen incorporation process and to obtain a production uniformity. To avoid these problems we investigated multilayer Ti/TiN films that show a high uniformity coupled with high quality factor, kinetic inductance and inertness of TiN. These features are ideal to realize superconductive microresonator detectors for astronomical instruments application but also for the field of neutrino physics. Using pure Ti and stoichiometric TiN, we developed and tested different multilayer configuration, in term of number of Ti/TiN layers and in term of different interlayer thicknesses. The target was to reach a critical temperature $T_C$ around $(1\div 1.5)$ K in order to have a low energy gap and slower recombination time (i.e. low generation-recombination noise). The results prove that the superconductive transition can be tuned in the $(0.5\div 4.6)$ K temperature range properly choosing the Ti thickness in the $(0\div 15)$ nm range, and the TiN thickness in the $(5\div 100)$ nm rang

Detection and distribution of European stone fruit yellows (ESFY) in apricot cv. ‘Bergeron’ and epidemiological studies in the province of Trento (Italy)

The aim was to investigate the performance of ‘Bergeron’ on ‘Wavit’ in 4 experimental fields, in the province of Trento (Italy), where European stone fruit yellows (ESFY) caused by “Candidatus Phytoplasma prunorum” has been constantly spreading since 2000.This included visual inspections for typical symptoms (early bud-break during dormancy and premature leaf-roll) and a highly sensitive Real time-PCR (Rt-PCR) assay. 25 % of the propagation material was checked with this method and found to be healthy, before planting in 2005.The epidemiology of the disease was also studied by focusing on: the presence of the vector Cacopsylla pruni (Scopoli) on conifers, the detection of “Ca. P. prunorum” in psyllid eggs and the transmission efficiency at different stages. This was done by exposing apricot trees in 2 locations, during 2 periods from January to July, to the overlapping presence in the orchards of the re-immigrants and the new generation of C. pruni. The results obtained demonstrated that ‘Bergeron’ seems to be highly susceptible to ESFY: typical bud-break was rarely observed, but up to 20-30% of the plants showed premature leaf-roll, fruit deformation and dieback. C. pruni was caught only once on Picea abies during winter; “Ca. P. prunorum” was found in 4 egg samples from 2 locations and the preliminary results on the exposed trees confirmed that the re-immigrants could be the most efficient vectors at least on apricot.Keywords: Prunus armeniaca, cultivar ‘Bergeron’, Real time-PCR, “Candidatus Phytoplasma prunorum”,epidemiolog

Understanding ligand binding selectivity in a prototypical GPCR family

Adenosine receptors are involved in many pathological conditions and are thus promising drug targets. However, developing drugs that target this GPCR subfamily is a challenging task. A number of drug candidates fail due to lack of selectivity which results in unwanted side effects. The extensive structural similarity of adenosine receptors complicates the design of selective ligands. The problem of selective targeting is a general concern in GPCRs and in this respect adenosine receptors are a prototypical example. Here we use enhanced sampling simulations to decipher the determinants of selectivity of ligands in A2a and A1 adenosine receptors. Our model shows how small differences in the binding pocket and in the water network around the ligand can be leveraged to achieve selectivity

Design, Synthesis and Discovery of N,N'-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

The recent outbreaks of Zika virus (ZIKV) infection worldwide make the discovery of novel antivirals against flaviviruses a research priority. This work describes the identification of novel inhibitors of ZIKV through a structure‐based virtual screening approach using the ZIKV NS5‐MTase. A novel series of molecules with a carbazoyl‐aryl‐urea structure has been discovered and a library of analogues has been synthesized. The new compounds inhibit ZIKV MTase with IC50 between 23–48 μM. In addition, carbazoyl‐aryl‐ureas also proved to inhibit ZIKV replication activity at micromolar concentration

Accounting for risk of non linear portfolios: a novel Fourier approach

The presence of non linear instruments is responsible for the emergence of non Gaussian features in the price changes distribution of realistic portfolios, even for Normally distributed risk factors. This is especially true for the benchmark Delta Gamma Normal model, which in general exhibits exponentially damped power law tails. We show how the knowledge of the model characteristic function leads to Fourier representations for two standard risk measures, the Value at Risk and the Expected Shortfall, and for their sensitivities with respect to the model parameters. We detail the numerical implementation of our formulae and we emphasizes the reliability and efficiency of our results in comparison with Monte Carlo simulation.Comment: 10 pages, 12 figures. Final version accepted for publication on Eur. Phys. J.

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

FUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. Our results unravel new pathomechanisms of FUS-ALS and identify a novel paradigm by which mutations in one RBP favor the formation of condensates sequestering other RBPs, affecting crucial biological functions, such as protein translation