University of Salento

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Author(s): Collaboration, The ATLAS; Aad, G; Abat, E; Abdallah, J; Abdelalim, AA; Abdesselam, A; Abdinov, O; Abi, BA; Abolins, M; Abramowicz, H; Acerbi, E; Acharya, BS; Achenbach, R; Ackers, M; Adams, DL; Adamyan, F; Addy, TN; Aderholz, M; Adorisio, C; Adragna, P; Aharrouche, M; Ahlen, SP; Ahles, F; Ahmad, A; Ahmed, H; Aielli, G; Åkesson, PF; Åkesson, TPA; Akimov, AV; Alam, SM; Albert, J; Albrand, S; Aleksa, M; Aleksandrov, IN; Aleppo, M; Alessandria, F; Alexa, C; Alexander, G; Alexopoulos, T; Alimonti, G; Aliyev, M; Allport, PP; Allwood-Spiers, SE; Aloisio, A; Alonso, J; Alves, R; Alviggi, MG; Amako, K; Amaral, P; Amaral, SP; Ambrosini, G; Ambrosio, G; Amelung, C; Ammosov, VV; Amorim, A; Amram, N; Anastopoulos, C; Anderson, B; Anderson, KJ; Anderssen, EC; Andreazza, A; Andrei, V; Andricek, L; Andrieux, M-L; Anduaga, XS; Anghinolfi, F; Antonaki, A; Antonelli, M; Antonelli, S; Apsimon, R; Arabidze, G; Aracena, I; Arai, Y; Arce, ATH; Archambault, JP; Arguin, J-F; Arik, E; Arik, M; Arms, KE; Armstrong, SR; Arnaud, M; Arnault, C; Artamonov, A; Asai, S; Ask, S

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

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J; L; P; P; J; M; T; L; M; J; V; K; I; J; D; T; P; T; Z; J; Z; V; V; R; S; V; T; K; J; M; V; B; I; V; P; V; Z; J; T; J; Z; Z; P; P; P; R; J; P; D; M; M; P; Z; S; V; I; D; R; J E; M; H; D; M; A; K; G; E; E; A; M; D; L J; A; G; E; M; M; V; L; L P; A S; R; A; Silva, P V M; M A B; C; F; A A; M; J M; F; P; G; P; R; Di Ciaccio, A; B; A; A; R; C; A; P; F; Di S; S; A; E; M; D; A; F; F; F; E; L; C; A; P; C; C; R; A; A; G; De D; De A; De G; Di A; Di A; C; S; P; S; S; E K; F; C; L; F; G; M; A; P; E; E; L; M; S; S; A; E F; P; R; S; M; H; F; C; N; M; M; L; A; de X; E; M; D; J; A I; Fleischmann, P; A; V; P F; C; S; C; W; E; J F; M; B; C; J P; R; A; D M; P; J; P; J; Z; P; M; D; V V; A; N I; S V; A G; S P; V N; R M; A B; V A; S N; S A; S V; V N; V N; A V; V V; A N; A G; A M; S V; V; V A; M E; A S; V V; A V; M S; A A; G Y; A M; A G; A V; A N; V; A A; V; E A; M; A P; A S; V G; A M; A V; V V; Booth, C N; Booth, P; D; Dawson, I; S D; R; R S; C; R; M C; P; P; N; M; S; D; R; E; K; D R; S; Zhu, H Z; S; P; I; K; M; I; M; V; T; W; U; M; I; R; S; S; S; C; D W; A; A; D; C; R K; K; B; A; D; H K; He, P; J; Y; R; D; A; R; Z; T; Lu, L; P; R R; R; A; Yang, J C; J; P; L; V; V; S; A; V P; S; L G; V P; S Y; F; V A; E; D M; I; A K; S M; B; S; F; L; A; B; R; G; J J; K; A; R L; M; J L; M; A; K J; P; B; Y; E; S; C; C; D; K; S; A; S O; Johansen, M; K E; K; J; D A; T; M; B; S B; J S H; L S; A F; K E; A T; M L; S; S C; Z; S C; D; Z; P K; S; Y; L; T; J; M; E G; H; G; N; G; M; O; Y; E; E; J; Y; Y; E; A; E; K; R; A; H; H; J; P; N; R; M; B; A; White, A; Yu, J; C; K; K; I A; A; A; C; D; I; U; C; S; M; M; N; M; Y; T; T; T; T; H; H; H; H; H; J; I; S; D C; A; P A; L S; B; K K; N K; P; Le C; Ma, L L; F K; J K; R; R S; Rosenbaum, G A; P; P; R J; W; K; Y; Y; T; Y; M; K; H; O; S; J; M; T; T; Y; Y; A; K; K; M; S; K; O; T; K; S; S; J; K; S; Y; A; H; Y; K; K; S H; T; A; Y; K; Y; F; W A; A; S; K; S; B S; D; M; De B; C; M P; H; L; L; C; N; R; E; T; M; M; C J; L; R; J; F; J; S; E; D; F; Segura, F; J; V; J V; M J; C S; C; F; A; 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Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.

A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is m_{H}=125.09±0.21 (stat)±0.11 (syst) GeV.

Over the last few years, the convincing forward steps in the development of Internet of Things (IoT)-enabling solutions are spurring the advent of novel and fascinating applications. Among others, mainly radio frequency identification (RFID), wireless sensor network (WSN), and smart mobile technologies are leading this evolutionary trend. In the wake of this tendency, this paper proposes a novel, IoT-aware, smart architecture for automatic monitoring and tracking of patients, personnel, and biomedical devices within hospitals and nursing institutes. Staying true to the IoT vision, we propose a smart hospital system (SHS), which relies on different, yet complementary, technologies, specifically RFID, WSN, and smart mobile, interoperating with each other through a Constrained Application Protocol (CoAP)/IPv6 over low-power wireless personal area network (6LoWPAN)/representational state transfer (REST) network infrastructure. The SHS is able to collect, in real time, both environmental conditions and patients’ physiological parameters via an ultra-low-power hybrid sensing network (HSN) composed of 6LoWPAN nodes integrating UHF RFID functionalities. Sensed data are delivered to a control center where an advanced monitoring application (MA) makes them easily accessible by both local and remote users via a REST web service. The simple proof of concept implemented to validate the proposed SHS has highlighted a number of key capabilities and aspects of novelty, which represent a significant step forward compared to the actual state of the art.

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented.

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{−1}$ at $\sqrt{s}$=7 TeV and 20 fb−1 at $\sqrt{s}$=8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

Abstract Electrospun nanofibers are extensively studied and their potential applications are largely demonstrated. Today, electrospinning equipment and technological solutions, and electrospun materials are rapidly moving to commercialization. Dedicated companies supply laboratory and industrial‐scale components and apparatus for electrospinning, and others commercialize electrospun products. This paper focuses on relevant technological approaches developed by research, which show perspectives for scaling‐up and for fulfilling requirements of industrial production in terms of throughput, accuracy, and functionality of the realized nanofibers. A critical analysis is provided about technological weakness and strength points in combination with expected challenges from the market. magnified image

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCCee) and an energy-frontier hadron collider (FCC-hh), which could,
\nsuccessively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also
\ninvestigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

The small GTP binding protein Rab7 has a role in the late endocytic pathway and lysosome biogenesis. The role of mammalian Rab7 in autophagy is, however, unknown. We have addressed this by inhibiting Rab7 function with RNA interference and overexpression of dominant negative Rab7. We show here that Rab7 was needed for the formation of preferably perinuclear, large aggregates, where the autophagosome marker LC3 colocalised with Rab7 and late endosomal and lysosomal markers. By electron microscopy we showed that these large aggregates corresponded to autophagic vacuoles surrounding late endosomal or lysosomal vesicles. Our experiments with quantitative electron microscopy showed that Rab7 was not needed for the initial maturation of early autophagosomes to late autophagic vacuoles, but that it participated in the final maturation of late autophagic vacuoles. Finally, we showed that the recruitment of Rab7 to autophagic vacuoles was retarded in cells deficient in the lysosomal membrane proteins Lamp1 and Lamp2, which we have recently shown to accumulate late autophagic vacuoles during starvation. In conclusion, our results showed a role for Rab7 in the final maturation of late autophagic vacuoles.

The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above 10 17 eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water Cherenkov particle detector stations spread over 3000 km 2 overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km 2 , 61-detector infilled array with 750 m spacing. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km 2 sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Observatory.

Hydrogels are macromolecular networks able to absorb and release water solutions in a reversible manner, in response to specific environmental stimuli. Such stimuli-sensitive behaviour makes hydrogels appealing for the design of ‘smart’ devices, applicable in a variety of technological fields. In particular, in cases where either ecological or biocompatibility issues are concerned, the biodegradability of the hydrogel network, together with the control of the degradation rate, may provide additional value to the developed device. This review surveys the design and the applications of cellulose-based hydrogels, which are extensively investigated due to the large availability of cellulose in nature, the intrinsic degradability of cellulose and the smart behaviour displayed by some cellulose derivatives.

and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

The final results of the search for the lepton flavour violating decay $$\mathrm {\mu }^+ \rightarrow \mathrm {e}^+ \mathrm {\gamma }$$ based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and totalling $$7.5\times 10^{14}$$ stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of $$ \mathcal{B} (\mu ^+ \rightarrow \mathrm{e}^+ \gamma ) < 4.2 \times 10^{-13}$$ (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.

We present the first results from the science demonstration phase for the Hi-GAL survey, the <i>Herschel<i/> key program that will map the inner Galactic plane of the Milky Way in 5 bands. We outline our data reduction strategy and present some science highlights on the two observed 2° × 2° tiles approximately centered at <i>l<i/> = 30° and <i>l<i/> = 59°. The two regions are extremely rich in intense and highly structured extended emission which shows a widespread organization in filaments. Source SEDs can be built for hundreds of objects in the two fields, and physical parameters can be extracted, for a good fraction of them where the distance could be estimated. The compact sources (which we will call cores' in the following) are found for the most part to be associated with the filaments, and the relationship to the local beam-averaged column density of the filament itself shows that a core seems to appear when a threshold around <i>A<i/><sub><i>V<i/><sub/> ~ 1 is exceeded for the regions in the <i>l<i/> = 59° field; a <i>A<i/><sub><i>V<i/><sub/> value between 5 and 10 is found for the <i>l<i/> = 30° field, likely due to the relatively higher distances of the sources. This outlines an exciting scenario where diffuse clouds first collapse into filaments, which later fragment to cores where the column density has reached a critical level. In spite of core L/M ratios being well in excess of a few for many sources, we find <i>core<i/> surface densities between 0.03 and 0.5 g cm<sup>-2<sup/>. Our results are in good agreement with recent MHD numerical simulations of filaments forming from large-scale converging flows.

Over the last decade, cadmium telluride (CdTe) and cadmium zinc telluride (CdZnTe) wide band gap semiconductors have attracted increasing interest as X-ray and gamma ray detectors. Among the traditional high performance spectrometers based on silicon (Si) and germanium (Ge), CdTe and CdZnTe detectors show high detection efficiency and good room temperature performance and are well suited for the development of compact and reliable detection systems. In this paper, we review the current status of research in the development of CdTe and CdZnTe detectors by a comprehensive survey on the material properties, the device characteristics, the different techniques for improving the overall detector performance and some major applications. Astrophysical and medical applications are discussed, pointing out the ongoing Italian research activities on the development of these detectors.

Hybrid halide perovskites represent one of the most promising solutions toward the fabrication of all solid nanostructured solar cells, with improved efficiency and long-term stability. This article aims at investigating the structural properties of iodide/chloride mixed-halide perovskites and correlating them with their photovoltaic performances. We found out that, independent of the components ratio in the precursor solution, Cl incorporation in an iodide-based structure, is possible only at relatively low concentration levels (below 3–4%). However, even if the material band gap remains substantially unchanged, the Cl doping dramatically improves the charge transport within the perovskite layer, explaining the outstanding performances of meso-superstructured solar cells based on this material.