High‐tuning‐range CMOS band‐pass IF filter based on a low‐Q cascaded biquad optimization technique

A design procedure for high‐order continuous‐time intermediate‐frequency band‐pass filters based on the cascade of low‐Q biquadratic cells is presented. The approach is well suited for integrated‐circuit fabrication, as it takes into account the maximum capacitance spread dictated by the available technology and maximum acceptable sensitivity to component variations. A trade‐off between noise and maximum linear range is also met. A novel, wide‐tuning‐range transconductor topology is also described. Based on these results, a 10‐pole band‐pass filter for a code division multiple‐access satellite receiver has been designed and tested. The filter provides tunable center frequency (f₀) from 10 to 70 MHz and exhibits a 28‐MHz bandwidth around f₀ = 70 MHz with more than 39‐dB attenuation at f₀/2 and 2f₀. Third‐order harmonic rejection is higher than 60 dB for a 1‐Vpp 70‐MHz input, and equivalent output noise is lower than 1 mV_rms. The circuit is fabricated in a 0.25‐µm complementary metal oxide semiconductor process, and the core consumes 12 mA from a 2.5‐V supply, offering the best current/pole ratio figure. The die area resulted to be 0.9 × 1.1 mm². Copyright © 2014 John Wiley & Sons, Ltd.     

Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Efficient estimation of extreme quantiles using adaptive kriging and importance sampling

This study considers an efficient method for the estimation of quantiles associated to very small levels of probability (up to O(10⁻⁹)), where the scalar performance function J is complex (eg, output of an expensive-to-run finite element model), under a probability measure that can be recast as a multivariate standard Gaussian law using an isoprobabilistic transformation. A surrogate-based approach (Gaussian Processes) combined with adaptive experimental designs allows to iteratively increase the accuracy of the surrogate while keeping the overall number of J evaluations low. Direct use of Monte-Carlo simulation even on the surrogate model being too expensive, the key idea consists in using an importance sampling method based on an isotropic-centered Gaussian with large standard deviation permitting a cheap estimation of small quantiles based on the surrogate model. Similar to AK-MCS as presented in the work of Schöbi et al., (2016), the surrogate is adaptively refined using a parallel infill criterion of an algorithm suitable for very small failure probability estimation. Additionally, a multi-quantile selection approach is developed, allowing to further exploit high-performance computing architectures. We illustrate the performances of the proposed method on several two to eight-dimensional cases. Accurate results are obtained with less than 100 evaluations of J on the considered benchmark cases.     

Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.     

An Innovative Science Gateway for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is currently building the next generation, ground-based, very high-energy gamma-ray instrumentation. CTA is expected to collect very large datasets (in the order of petabytes) which will have to be stored, managed and processed. This paper presents a graphical user interface built inside a science gateway aiming at providing CTA-users with a common working framework. The gateway is WS-PGRADE/gUSE workflow-oriented and is equipped with a flexible SSO (based on SAML) to control user access for authentication and authorization. An interactive desktop environment is provided, called Astronomical & Physics Cloud Interactive Desktop (ACID). Users are able to exploit the graphical interface as provided natively by the tools included in ACID. A cloud data service shares and synchronizes data files and output results between the user desktop and the science gateway. Our solution is a first attempt towards an ecosystem of new technologies with a high level of flexibility to suit present and future requirements of the CTA community.     

Influence of free carbon on the Young's modulus and hardness of polymer-derived silicon oxycarbide glasses

Silicon oxycarbide (SiOC) glasses in the form of thin, dense, and crack-free samples were fabricated according to the polymer pyrolysis route starting from cross-linked polysiloxane. The amount of free carbon in the final SiOC materials was varied in the range 18-60 vol%. The mechanical properties of the SiOC glasses were measured by nanoindentaion technique and revealed that both the Young's modulus and the hardness decrease with increase in the free carbon content and follow a simple rule of mixtures model.