PacDOCK: A Web Server for Positional Distance-Based and Interaction-Based Analysis of Docking Results

Molecular docking is a key method for structure-based drug design used to predict the conformations assumed by small drug-like ligands when bound to their target. However, the evaluation of molecular docking studies can be hampered by the lack of a free and easy to use platform for the complete analysis of results obtained by the principal docking programs. To this aim, we developed PacDOCK, a freely available and user-friendly web server that comprises a collection of tools for positional distance-based and interaction-based analysis of docking results, which can be provided in several file formats. PacDOCK allows a complete analysis of molecular docking results through root mean square deviation (RMSD) calculation, molecular visualization, and cluster analysis of docked poses. The RMSD calculation compares docked structures with a reference structure, also when atoms are randomly labelled, and their conformational and positional differences can be visualised. In addition, it is possible to visualise a ligand into the target binding pocket and investigate the key receptor-ligand interactions. Moreover, PacDOCK enables the clustering of docking results by identifying a restrained number of clusters from many docked poses. We believe that PacDOCK will contribute to facilitating the analysis of docking results to improve the efficiency of computer-aided drug design

How the italian residential sector could contribute to load flexibility in demand response activities: a methodology for residential clustering and developing a flexibility strategy

This work aims at exploring the potential contribution of the Italian residential sector in implementing load flexibility for Demand Response activities. In detail, by combining experimental and statistical approaches, a method to estimate the load profile of a dwelling cluster of 751 units has been presented. To do so, 14 dwelling archetypes have been defined and the algorithm to categorise the sample units has been built. Then, once the potential flexible loads for each archetype have been evaluated, a control strategy for applying load time shifting has been implemented. That strategy accounts for both the power demand profile and the hourly electricity price. Specifically, it has been assumed that end users access a pricing mechanism following the hourly trend of electricity economic value, which is traded day by day in the Italian spot market, instead of the current Time of Use (TOU) system. In such a way, it is possible to flatten the dwellings cluster profile, limiting undesired and unexpected results on the balancing market. In the end, monthly and yearly flexibility indexes have been defined along with the strategy effectiveness parameter. From calculations, it emerges that a dwelling cluster for the Italian residential sector is characterised by a flexibility index of 10.3% and by a strategy effectiveness equal to 34%. It is noteworthy that the highest values for flexibility purpose have been registered over the heating season (winter) for the weekends

Surgical management of adult Brainstem Gliomas: a systematic review and meta-analysis

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy

Particle profiling of EV‐lipoprotein mixtures by AFM nanomechanical imaging

The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one of the main obstacles for the isolation and characterization of these pervasive biogenic lipid nanoparticles. We herein present the application of an atomic force microscopy (AFM)-based quantitative morphometry assay to the rapid nanomechanical screening of mixed LPs and EVs samples. The method can determine the diameter and the mechanical stiffness of hundreds of individual nanometric objects within few hours. The obtained diameters are in quantitative accord with those measured via cryo-electron microscopy (cryo-EM); the assignment of specific nanomechanical readout to each object enables the simultaneous discrimination of co-isolated EVs and LPs even if they have overlapping size distributions. EVs and all classes of LPs are shown to be characterised by specific combinations of diameter and stiffness, thus making it possible to estimate their relative abundance in EV/LP mixed samples in terms of stoichiometric ratio, surface area and volume. As a side finding, we show how the mechanical behaviour of specific LP classes is correlated to distinctive structural features revealed by cryo-EM. The described approach is label-free, single-step and relatively quick to perform. Importantly, it can be used to analyse samples which prove very challenging to assess with several established techniques due to ensemble-averaging, low sensibility to small particles, or both, thus providing a very useful tool for quickly assessing the purity of EV/LP isolates including plasma- and serum-derived preparations

Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy

Probabilistic tsunami forecasting for early warning

Tsunami warning centres face the challenging task of rapidly forecasting tsunami threat immediately after an earthquake, when there is high uncertainty due to data deficiency. Here we introduce Probabilistic Tsunami Forecasting (PTF) for tsunami early warning. PTF expli- citly treats data- and forecast-uncertainties, enabling alert level definitions according to any predefined level of conservatism, which is connected to the average balance of missed-vs- false-alarms. Impact forecasts and resulting recommendations become progressively less uncertain as new data become available. Here we report an implementation for near-source early warning and test it systematically by hindcasting the great 2010 M8.8 Maule (Chile) and the well-studied 2003 M6.8 Zemmouri-Boumerdes (Algeria) tsunamis, as well as all the Mediterranean earthquakes that triggered alert messages at the Italian Tsunami Warning Centre since its inception in 2015, demonstrating forecasting accuracy over a wide range of magnitudes and earthquake types

Il Centro Allerta Tsunami (CAT) dell’INGV

The Tsunami Alert Centre of the INGV (CAT-INGV) was created with the aim of contributing to the mitigation of the risk due to tsunamis triggered by earthquakes on the Italian and Mediterranean coasts. Tsunamis of seismic origin, in addition to being the most frequent, are those that can be detected more quickly. Seismic waves, in fact, travel in the crust with a much higher speed than that of tsunami waves. With effective seismic networks connected in real time, an "Early Warning" system can be implemented, i.e. a system capable of sending an alert signal before the arrival of the tsunami waves, at least from a certain distance from the source. The CAT-INGV has two main tasks. The first one is to provide alerts to the competent authorities in the event of potential tsunamigenic earthquakes in the Mediterranean, taking into account the criteria defined by the Department of Civil Protection for this purpose. The second one consists in carrying out the necessary studies for the definition of the probabilistic danger of tsunamis for the Italian coasts, starting from those of seismic origin (Seismic Probabili-stic Tsunami Hazard Analysis, SPTHA). In this contribution the first aspect is described, while the realization of the studies on hazard at the Mediterranean scale is the subject of research described in various recent articles (Lorito et al., 2015; Grezio et al., 2017; Selva et al., 2017a; Selva et al., 2017b). The TSUMAPS-NEAM project, funded by the European Commission and concluded at the end of 2017, provided the first hazard map for the Mediterranean region and the north-east Atlantic (Basili et al., 2017).Published91-975T. Modelli di pericolosità sismica e da maremotoN/A or not JC

MYC Rearranged Aggressive B-Cell Lymphomas: A Report on 100 Patients of the Fondazione Italiana Linfomi (FIL)

Supplemental Digital Content is available in the text

The Italian Earthquakes and Tsunami Monitoring and Surveillance Systems

The Osservatorio Nazionale Terremoti (ONT) is the Italian seismic operational centre for monitoring earthquake, it is part of Istituto Nazionale di Geofisica e Vulcanologia (INGV) the largest Italian research institution, with focus in Earth Sciences. INGV runs the Italian National Seismic Network (network code IV) and other networks at national scale for monitoring earthquakes and tsunami. INGV is a primary node of European Integrated Data Archive (EIDA) for archiving and distributing, continuous, quality checked seismic waveforms (strong motion and weak motion recordings). ONT designed the data acquisition system to accomplish, in near-real-time, automatic earthquake detection, hypocentre and magnitude determination and evaluation of moment tensors, shake maps and other products. Database archiving of all parametric results are closely linked to the existing procedures of the INGV seismic monitoring environment and surveillance procedures. ONT organize the Italian earthquake surveillance service and the tsunami alert service (INGV is Tsunami Service Provider of the ICG/NEAM for the entire Mediterranean basin). We provide information to the Dipartimento di Protezione Civile (DPC) and to several Mediterranean countries. Earthquakes information are revised routinely by the analysts of the Italian Seismic Bulletin. The results are published on the web and are available to the scientific community and the general public.PublishedMontreal1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunam