Experimental and modelling studies for the validation of the mechanistic basis of the Local Effect Model

This review will summarize results obtained in the recent years applying the Local Effect Model (LEM) approach to the study of basic radiobiological aspects, as for instance DNA damage induction and repair, and charged particle track structure. The promising results obtained using different experimental techniques and looking at different biological end points, support the relevance of the LEM approach for the description of radiation effects induced by both lowand high-LET radiation. Furthermore, they suggest that nowadays the appropriate combination of experimental and modelling tools can lead to advances in the understanding of several open issues in the field of radiation biology

Proton beam characterization in the experimental room of the Trento Proton Therapy facility

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106–109 particles/s down to 101–105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments

Fiscal sustainability and policy implications for the euro area.

In this paper we examine the sustainability of euro area public finances against the backdrop of population ageing. We critically assess the widely used projections of the Working Group on Ageing Populations (AWG) of the EU's Economic Policy Committee and argue that ageing costs may be higher than projected in the AWG reference scenario. Taking into account adjusted headline estimates for ageing costs, largely based upon the sensitivity analysis carried out by the AWG, we consider alternative indicators to quantify sustainability gaps for euro area countries. With respect to the policy implications, we assess the appropriateness of different budgetary strategies to restore fiscal sustainability taking into account intergenerational equity. Our stylised analysis based upon the lifetime contribution to the government's primary balance of different generations suggests that an important degree of pre-funding of the ageing costs is necessary to avoid shifting the burden of adjustment in a disproportionate way to future generations. For many euro area countries this implies that the medium-term targets defined in the context of the revised stability and growth pact would ideally need to be revised upwards to significant surpluses.Population Ageing ; Fiscal Sustainability ; Generational Accounting ; Medium-term Objectives for Fiscal Policy

10-GHz fully differential Sallen–Key lowpass biquad filters in 55nm SiGe BICMOS technology

Multi-GHz lowpass filters are key components for many RF applications and are required for the implementation of integrated high-speed analog-to-digital and digital-to-analog converters and optical communication systems. In the last two decades, integrated filters in the Multi-GHz range have been implemented using III-V or SiGe technologies. In all cases in which the size of passive components is a concern, inductorless designs are preferred. Furthermore, due to the recent development of high-speed and high-resolution data converters, highly linear multi-GHz filters are required more and more. Classical open loop topologies are not able to achieve high linearity, and closed loop filters are preferred in all applications where linearity is a key requirement. In this work, we present a fully differential BiCMOS implementation of the classical Sallen Key filter, which is able to operate up to about 10 GHz by exploiting both the bipolar and MOS transistors of a commercial 55-nm BiCMOS technology. The layout of the biquad filter has been implemented, and the results of post-layout simulations are reported. The biquad stage exhibits excellent SFDR (64 dB) and dynamic range (about 50 dB) due to the closed loop operation, and good power efficiency (0.94 pW/Hz/pole) with respect to comparable active inductorless lowpass filters reported in the literature. Moreover, unlike other filters, it exploits the different active devices offered by commercial SiGe BiCMOS technologies. Parametric and Monte Carlo simulations are also included to assess the robustness of the proposed biquad filter against PVT and mismatch variations

An improved reversed miller compensation technique for three-stage CMOS OTAs with double pole-zero cancellation and almost single-pole frequency response

This paper presents an improved reversed nested Miller compensation technique exploiting a single additional feed-forward stage to obtain double pole-zero cancellation and ideally single-pole behavior, in a three-stage Miller amplifier. The approach allows designing a three-stage operational transconductance amplifier (OTA) with one dominant pole and two (ideally) mutually cancelling pole-zero doublets. We demonstrate the robustness of the proposed cancellation technique, showing that it is not significantly influenced by process and temperature variations. The proposed design equations allow setting the unity-gain frequency of the amplifier and the complex poles' resonance frequency and quality factor. We introduce the notion of bandwidth efficiency to quantify the OTA performance with respect to a telescopic cascode OTA for given load capacitance and power consumption constraints and demonstrate analytically that the proposed approach allows a bandwidth efficiency that can ideally approach 100%. A CMOS implementation of the proposed compensation technique is provided, in which a current reuse scheme is used to reduce the total current consumption. The OTA has been designed using a 130-nm CMOS process by STMicroelectronics and achieves a DC gain larger than 120 dB, with almost single-pole frequency response. Monte Carlo simulations have been performed to show the robustness of the proposed approach to process, voltage, and temperature (PVT) variations and mismatches

An ultra-low-voltage class-AB OTA exploiting local CMFB and body-to-gate interface

In this work a novel bulk-driven (BD) ultra-low-voltage (ULV) class-AB operational transconductance amplifier (OTA) which exploits local common mode feedback (LCMFB) strategies to enhance performance and robustness against process, voltage and temperature (PVT) variations has been proposed. The amplifier exploits body-to-gate (B2G) interface to increase the slew rate and attain class-AB behaviour, whereas two pseudo-resistors have been employed to increase the common mode rejection ratio (CMRR). The architecture has been extensively tested through Monte Carlo and PVT simulations, results show that the amplifier is very robust in terms of gain-bandwidth-product (GBW), power consumption and slew rate. A wide comparison against state-of-the-art has pointed out that best small-signal figures of merit are attained and good large-signal performance is guaranteed, also when worst-case slew rate is considered

Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

The aim of this study was to determine whether low prevalence human papillomavirus (HPV) 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS) stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis) and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein