Role of plasma-induced defects in the generation of 1/f noise in graphene

It has already been reported that 1/f noise in graphene can be dominated by fluctuations of charge carrier mobility. We show here that the increasing damage induced by oxygen plasma on graphene samples result in two trends: at low doses, the magnitude of the 1/f noise increases with the dose; and at high doses, it decreases with the dose. This behaviour is interpreted in the framework of 1/f noise generated by carrier mobility fluctuations where the concentration of mobility fluctuation centers and the mean free path of the carriers are competing factors. Published by AIP Publishing

Realization of the farad from the dc quantum Hall effect with digitally-assisted impedance bridges

A new traceability chain for the derivation of the farad from dc quantum Hall effect has been implemented at INRIM. Main components of the chain are two new coaxial transformer bridges: a resistance ratio bridge, and a quadrature bridge, both operating at 1541 Hz. The bridges are energized and controlled with a polyphase direct-digital-synthesizer, which permits to achieve both main and auxiliary equilibria in an automated way; the bridges and do not include any variable inductive divider or variable impedance box. The relative uncertainty in the realization of the farad, at the level of 1000 pF, is estimated to be 64E-9. A first verification of the realization is given by a comparison with the maintained national capacitance standard, where an agreement between measurements within their relative combined uncertainty of 420E-9 is obtained.Comment: 15 pages, 11 figures, 3 table

Impact of resistance mutations on virological efficacy of DTG-based maintenance two-drug regimens: an ARCA cohort study

Background: Two-drug regimens (2DR) are largely prescribed as maintenance therapy, nowadays mainly based on DTG. While many data have been reported about PI-based 2DR, the impact of resistance mutations and duration of virological suppression on DTG-based 2DR remains to be clarified. The aim of this study was to evaluate the impact of resistance mutations on virological outcome of DTG-based 2DR maintenance ART. Material and methods: Virologically suppressed patients (pts) switching to DTG+3TC or DTG+RPV with pre-baseline (time of switch=baseline, BL) resistance genotype (at least PR/RT) were selected from the ARCA database. Primary endpoint was virological failure (VF: an HIV-RNA, VL, >200 cps/mL or 2 consecutive >50 cps/mL). The probability of VF was estimated by Kaplan-Meier analysis. Resistance to 2DR was defined as occurrence of at least Stanford HIVdb (v.8.5) low-level resistance (LLR) to at least one drug included in the current 2DR, based on cumulative genotype. CD4 changes were assessed using Student’s t- test for paired samples. A secondary analysis comparing 2DR with DTG-based 3D regimens was also performed. Results: A total of 318 2DR pts were analysed: 260 (82%) switching to DTG+3TC, 58 (18%) to DTG+RPV; 68% were males, median age was 51 (44-56) years, 12 (6-23) years of HIV infection, 5 (3-8) years of virological suppression, nadir CD4 231 (121-329), 5 (3-9) previous ARV lines, 59% previously exposed to INSTI, 11% with resistance to current 2DR. The integrase sequence was available in 14% of patients, none harbouring resistance to DTG. 20 VF were observed, of whom 4 (3/17 VF in DTG+3TC, 1/3 in DTG+RPV) in patients with at least LLR at BL (M184V+K219Q; D67N+K70R+K219Q; D67N+K70R+T215Y+219Q; E138A), in a median FU of 1.3 years (IQR 0.6-2). The 2-year estimated probability of VF was 8.7% (95% CI 4.4;13); 8.6% (4.1;13.1) in those without resistance and 9.7% (-4.4;23.8) in those with resistance (Log rank: p=ns, figure 1). No factor was significantly associated with VF at multivariate analysis, but in pts with <6 years of virological suppression, BL resistance was associated with a higher probability of VF (p=0.003). After 48 weeks, a statistically significant increase in CD4+ was detected (+56 cells/mmc, p<0.001), independently from baseline resistance. The 2-year estimated probability of VF in the reference 3DR group (n=564) was not different from that for the 2DR group: 8.8% (5.9;11.7) in the whole case file and 9.7% (6.6;12.8) in the presence of baseline resistance. Longer time of virological suppression was the only factor associated with a lower risk of VF in the 3DR dataset. Conclusions: DTG-based 2DRs show high virological efficacy, even in the context of predicted incomplete activity, at least within a short-term follow-up. A longer duration of virological suppression seems to decrease the impact of resistance on virological outcome, however further studies are warranted to confirm this hypothesis and possibly define a clinically useful threshold

High-throughput confocal imaging of differentiated 3D liver-like spheroid cellular stress response reporters for identification of drug-induced liver injury liability

Adaptive stress response pathways play a key role in the switch between adaptation and adversity, and are important in drug-induced liver injury. Previously, we have established an HepG2 fluorescent protein reporter platform to monitor adaptive stress response activation following drug treatment. HepG2 cells are often used in high-throughput primary toxicity screening, but metabolizing capacity in these cells is low and repeated dose toxicity testing inherently difficult. Here, we applied our bacterial artificial chromosome-based GFP reporter cell lines representing Nrf2 activation (Srxn1-GFP and NQO1-GFP), unfolded protein response (BiP-GFP and Chop-GFP), and DNA damage response (p21-GFP and Btg2-GFP) as long-term differentiated 3D liver-like spheroid cultures. All HepG2 GFP reporter lines differentiated into 3D spheroids similar to wild-type HepG2 cells. We systematically optimized the automated imaging and quantification of GFP reporter activity in individual spheroids using high-throughput confocal microscopy with a reference set of DILI compounds that activate these three stress response pathways at the transcriptional level in primary human hepatocytes. A panel of 33 compounds with established DILI liability was further tested in these six 3D GFP reporters in single 48 h treatment or 6 day daily repeated treatment. Strongest stress response activation was observed after 6-day repeated treatment, with the BiP and Srxn1-GFP reporters being most responsive and identified particular severe-DILI-onset compounds. Compounds that showed no GFP reporter activation in two-dimensional (2D) monolayer demonstrated GFP reporter stress response activation in 3D spheroids. Our data indicate that the application of BAC-GFP HepG2 cellular stress reporters in differentiated 3D spheroids is a promising strategy for mechanism-based identification of compounds with liability for DILI

Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis

BackgroundGiven that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset.MethodsData from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that.ResultsA total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively).ConclusionsWe identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis

Response to isolated limb perfusion and chemotherapy with epirubicin plus ifosfamide in a metastatic malignant ossifying fibromyxoid tumor

Background: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain lineage and intermediate biological potential. It is more common in middle-aged men, usually arising from the deep tissues of the extremities. It is now established that it is a translocation related tumor, most often marked by translocation of PHF1 gene. Surgery is the mainstay of treatment and proves usually curative, although, in rarer cases the disease shows malignant features and tendency to recur both locally and at distant sites. In such cases, no standard treatment exists. Case presentation: We report on a case of malignant advanced OFMT of the hand with lung metastases responding to isolated limb perfusion with human recombinant tumor necrosis factor and melphalan and chemotherapy with epirubicin and ifosfamide. Conclusions: To our knowledge, this is the first report of activity of soft tissue sarcoma-oriented chemotherapy in advanced OFMT

A Comparison of Four Probability-Based Online and Mixed-Mode Panels in Europe

Inferential statistics teach us that we need a random probability sample to infer from a sample to the general population. In online survey research, however, volunteer access panels, in which respondents self-select themselves into the sample, dominate the landscape. Such panels are attractive due to their low costs. Nevertheless, recent years have seen increasing numbers of debates about the quality, in particular about errors in the representativeness and measurement, of such panels. In this article, we describe four probability-based online and mixed-mode panels for the general population, namely, the Longitudinal Internet Studies for the Social Sciences (LISS) Panel in the Netherlands, the German Internet Panel (GIP) and the GESIS Panel in Germany, and the Longitudinal Study by Internet for the Social Sciences (ELIPSS) Panel in France. We compare them in terms of sampling strategies, offline recruitment procedures, and panel characteristics. Our aim is to provide an overview to the scientific community of the availability of such data sources to demonstrate the potential strategies for recruiting and maintaining probability-based online panels to practitioners and to direct analysts of the comparative data collected across these panels to methodological differences that may affect comparative estimates

Experimental Characterization of RF-SQUIDs Based Josephson Traveling Wave Parametric Amplifier Exploiting Resonant Phase Matching Scheme

This study presents recent advancements in Josephson Traveling Wave Parametric Amplifiers (JTWPAs) developed and tested at Istituto Nazionale di Ricerca Metrologica within the Detector Array Readout with Traveling Wave AmplifieRS project framework. Combining Josephson junctions with superconducting coplanar waveguides, JTWPAs offer advanced capabilities for quantum-limited broadband microwave amplification and the emission of non-classical microwave radiation. The work delves into the architecture, optimization, and experimental characterization of a JTWPA with a Resonant Phase-Matching mechanism, highlighting signal gains and idler conversion factors in relation to pump power and signal frequency