Targeted phenolic profile of radler beers by HPLC-ESI-MS/MS: the added value of hesperidin to beer antioxidants

The well-known health beneficial properties of beer are mainly due to phenolic antioxidants. Citrus-flavored beers represent a growing side-market in the beer industry, sparingly investigated to date. The phenolic profile of commercial radler beers (R1, R2) was investigated to evaluate the impact of the lemon juice added to beer in the industrial production. Results were compared to those obtained for opportunely chosen commercial beer (B) and lemonade (L). The study was carried out by an HPLC-MS/MS with an electrospray ionization source in selected ion recording mode, analyzing in a single chromatographic run 26 compounds belonging to the different phenolic classes of hydroxybenzoic, hydroxycinnamic and caffeoylquinic acids, flavonoids and prenylflavonoids. Different phenolic profiles were found for R1 and R2, mainly ascribed to different malt/hop/recipe used for the beer. High to very high level of hesperidin were found in the radlers, so that a major impact on phenolic antioxidants of the radlers was due to the lemon. Similarly, a major impact of the lemon aromas was found, D-limonene being the dominant peak resulting from the GC-MS analysis of the volatile fraction of the radlers. Graphical Abstract: [Figure not available: see fulltext.]

Study of Innovative GO/PBI Composites as Possible Proton Conducting Membranes for Electrochemical Devices

The appeal of combining polybenzimidazole (PBI) and graphene oxide (GO) for the manufacturing of membranes is increasingly growing, due to their versatility. Nevertheless, GO has always been used only as a filler in the PBI matrix. In such context, this work proposes the design of a simple, safe, and reproducible procedure to prepare self-assembling GO/PBI composite membranes characterized by GO-to-PBI (X:Y) mass ratios of 1:3, 1:2, 1:1, 2:1, and 3:1. SEM and XRD suggested a homogenous reciprocal dispersion of GO and PBI, which established an alternated stacked structure by mutual π-π interactions among the benzimidazole rings of PBI and the aromatic domains of GO. TGA indicated a remarkable thermal stability of the composites. From mechanical tests, improved tensile strengths but worsened maximum strains were observed with respect to pure PBI. The preliminary evaluation of the suitability of the GO/PBI X:Y composites as proton exchange membranes was executed via IEC determination and EIS. GO/PBI 2:1 (IEC: 0.42 meq g−1; proton conductivity at 100 °C: 0.0464 S cm−1) and GO/PBI 3:1 (IEC: 0.80 meq g−1; proton conductivity at 100 °C: 0.0451 S cm−1) provided equivalent or superior performances with respect to similar PBI-based state-of-the-art materials

Testing general relativity by means of ring lasers

The paper discusses the optimal conguration of one or more ring lasers to be used for measuring the general relativistic effects of the rotation of the Earth, as manifested on the surface of the planet. The analysis is focused on devices having their normal vector lying in the meridian plane. The crucial role of the evaluation of the angles is evidenced. Special attention is paid to the orientation at the maximum signal, minimizing the sensitivity to the orientation uncertainty. The use of rings at different latitudes is mentioned and the problem of the non-sphericity of the Earth is commented

Testing general relativity by means of ring lasers

The paper discusses the optimal conguration of one or more ring lasers to be used for measuring the general relativistic effects of the rotation of the Earth, as manifested on the surface of the planet. The analysis is focused on devices having their normal vector lying in the meridian plane. The crucial role of the evaluation of the angles is evidenced. Special attention is paid to the orientation at the maximum signal, minimizing the sensitivity to the orientation uncertainty. The use of rings at different latitudes is mentioned and the problem of the non-sphericity of the Earth is commented

Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy

Purpose: Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose combination antibiotic approved in Europe and the United States for patients with hospitalacquired pneumonia, including ventilator-associated pneumonia (HAP/VAP). The economic benefits of a new drug such as CAZ-AVI are required to be assessed against those of available comparators, from the perspective of health care providers and payers, through cost-effectiveness and cost-utility analyses. The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092). Methods: A patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analysis focused on direct medical costs. The time horizon of the model selected was 5 years, with an annual discount rate of 3% on costs and quality-adjusted life-years (QALYs). Clinical inputs for treatment comparisons were mainly obtained from the REPROVE clinical study data. In addition to clinical outcomes observed in the trial, the model incorporated impact of resistance pathogens, based on data from published studies and expert opinion. Certain assumptions were made for some model parameters due to a lack of data. Findings: The analysis demonstrated that the intervention sequence (CAZ-AVI followed by colistin + high-dose meropenem) versus the comparator sequence (meropenem followed by colistin + high-dose meropenem) provided a better clinical cure rate (+13.52%), which led to a shorter hospital stay (−0.40 days per patient), and gains in the number of life-years (+0.195) and QALYs (+0.350) per patient. The intervention sequence had an estimated net incremental total cost of V1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was V3581 ($4000) per QALY gained, well below the willingness-topay threshold of V30,000 ($33,507) per QALY in Italy. Implications: The model results showed that CAZAVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem

Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region

Acknowledgements We thank all members of the Di Virgilio lab for their feedback and discussion; V Delgado-Benito (Di Virgilio lab, MDC, Berlin) for her contribution to the project development; L Keller (Di Virgilio lab, MDC, Berlin) for support with cloning, mutagenesis, and mice genotyping; C Brischetto (Scheidereit Lab, MDC, Berlin) for assistance with confocal microscopy; Aberdeen Proteomics facility (University of Aberdeen) for the mass spec analysis of Aph-induced hRIF1 phosphorylation; and the MDC FACS Core Facility and Dr. HP Rahn for support with cell sorting. Aliquots of ATRi and ATMi were gener- ously provided by AG Henssen (MDC and ECRC, Berlin). Figures 1B and D, 2A, and 4C contain items created with BioRender.com. This work was supported by ERC grant 638897 (to MDV), the Helmholtz- Gemeinschaft Zukunftsthema 'Immunology and Inflammation' ZT-0027 (to MDV), P41 GM109824 and P41 GM103314 (to BTC), and Cancer Research UK awards C1445/A19059 and DRCPGM\100,013 (to ADD and SH).Peer reviewedPublisher PD

A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells

Background: An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials. Methods: Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy. Results: Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent. Conclusion: Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin

GINGER

In this paper, we outline the scientific objectives, the experimental layout, and the collaborations envisaged for the GINGER (Gyroscopes IN GEneral Relativity) project. The GINGER project brings together different scientific disciplines aiming at building an array of Ring Laser Gyroscopes (RLGs), exploiting the Sagnac effect, to measure continuously, with sensitivity better than picorad/ s, large bandwidth (ca. 1 kHz), and high dynamic range, the absolute angular rotation rate of the Earth. In the paper, we address the feasibility of the apparatus with respect to the ambitious specifications above, as well as prove how such an apparatus, which will be able to detect strong Earthquakes, very weak geodetic signals, as well as general relativity effects like Lense-Thirring and De Sitter, will help scientific advancements in Theoretical Physics, Geophysics, and Geodesy, among other scientific fields.Comment: 21 pages, 9 figure

Measuring gravito-magnetic effects by multi ring-laser gyroscope

We propose an under-ground experiment to detect the general relativistic effects due to the curvature of space-time around the Earth (de Sitter effect) and to the rotation of the planet (dragging of the inertial frames or Lense-Thirring effect). It is based on the comparison between the IERS value of the Earth rotation vector and corresponding measurements obtained by a tri-axial laser detector of rotation. The proposed detector consists of six large ring-lasers arranged along three orthogonal axes. In about two years of data taking, the 1% sensitivity required for the measurement of the Lense-Thirring drag can be reached with square rings of 6 m side, assuming a shot noise limited sensitivity (20prad/s/sqrt(Hz). The multi-gyros system, composed of rings whose planes are perpendicular to one or the other of three orthogonal axes, can be built in several ways. Here, we consider cubic and octahedral structures. It is shown that the symmetries of the proposed configurations provide mathematical relations that can be used to ensure the long term stability of the apparatus