Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

STRONG MEDIUM AND COUNTERION EFFECTS UPON THE REDOX POTENTIAL OF THE 12-TUNGSTOCOBALTATE(III/II) COUPLE

The 12-tungstocobaltate(III/II) redox couple, both oxidation states being highly negatively charged (5-/6-), is strongly influenced by the nature of the counterion present. In particular, tetraalkylammonium ions decrease E-degrees[Co(III)/(II)] significantly, relative to that measured in the presence of alkali-metal ions in an organic solvent such as acetonitrile, thus causing large decreases in redox reactivity with respect to oxidation. An increasing proportion of water in the solvent increases E-degrees. The redox properties of the hexachloroiridate(IV)/(III) couple are affected by cations in a similar way

Insight into the Mechanism of Intramolecular Inhibition of the Catalytic Activity of Sirtuin 2 (SIRT2)

Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase that has been associated with neurodegeneration and cancer. SIRT2 is composed of a central catalytic domain, the structure of which has been solved, and N- and C-terminal extensions that are thought to control SIRT2 function. However structural information of these N- and C-terminal regions is missing. Here, we provide the first full-length molecular models of SIRT2 in the absence and presence of NAD+. We also predict the structural alterations associated with phosphorylation of SIRT2 at S331, a modification that inhibits catalytic activity. Bioinformatics tools and molecular dynamics simulations, complemented by in vitro deacetylation assays, provide a consistent picture based on which the C-terminal region of SIRT2 is suggested to function as an autoinhibitory region. This has the capacity to partially occlude the NAD+ binding pocket or stabilize the NAD+ in a non-productive state. Furthermore, our simulations suggest that the phosphorylation at S331 causes large conformational changes in the C-terminal region that enhance the autoinhibitory activity, consistent with our previous findings that phosphorylation of S331 by cyclin-dependent kinases inhibits SIRT2 catalytic activity. The molecular insight into the role of the C-terminal region in controlling SIRT2 function described in this study may be useful for future design of selective inhibitors targeting SIRT2 for therapeutic applications

Reactions of an indolinonic nitroxide with superoxide radical anion in the presence of alkylhalides. Unexpected formation of a reduced transposed product

This study concerns the reactions of 2-methyl-2-phenyl-3-phenylimino-2,3-dihydroindol-l-oxyl and 2,2,6,6-tetramethylpiperidine-1-oxyl with alkylperoxyls, generated from potassium superoxide and a series of alkylhalides, in order to evaluate possible differences in reactivity with primary, secondary and tertiary alkylperoxyls. To better understand the reactivity of the studied indolinonic aminoxyl in alkaline medium, the investigation was extended to its reactions with potassium hydroxide and potassium tert-butoxide in different solvents

Antioxidant activity of pomegranate juices from different geographical origin and cultivar

Punica granatum L. (Punicaceae), commonly known as pomegranate, is a deciduous shrub cultivated throughout the world and in particular in the Mediterranean area. The fruits arils are consumed fresh or transformed into fresh juices, beverages, jellies and flavoring or coloring agents. This fruits has achieved great attention for its health benefits in the last years [1]. In fact, pomegranate juice has shown significant antiatherosclerotic, anti-hypertensive, antioxidant, and anti-inflammatory effects in human subjects and mouse models [1]. A wide variety of compounds, and among these ellagic acid, ellagitannins (including punicalagina), punicic acid, anthocyanins, flavonols, flavan-3-ols and flavones that show a great antioxidant activity appear to be mainly responsible for its beneficial effects, but several factors such as cultivars, agro-climatic conditions, fertilizer, irrigation, fruit maturity, storage and postharvest treatments influence the quality attributes of pomegranate [2]. For these reasons we studied the antioxidant activity of juices obtained pressing aryls or pulps of pomegranate fruits from various cultivars and from different geographic areas. Seventeen samples of pomegranate fruit, were analyzed, which included Mollar (from Italy and Spain), Wonderful (from Israel, Egypt, USA, Peru and Italy), Bhagwa from India, Herskovitz from South Africa, Hicaznar from Turkey, some Italian local accessions and finally one sample from Tunisia with undefined cultivar. Furthermore, for comparison, we also analysed juice obtained from red oranges and bottled orange and pomegranate juices. Total antioxidant capacity by ABTS assay, Oxygen Radical Absorbance Capacity (ORAC), Total Phenolic Content (TPC), Total Anthocyanin Content (TAC) were measured. The results show that the antioxidant content of the pulp juices (peels and membranes) is ≈ 50 times greater than those of the aryls. Differences related to the botanical and geographical origin were also observed

Attività Antiossidante e Colore di Mieli Unifloreali e Multiflorali della Regione Marche.

Il miele è uno degli alimenti più complessi prodotto dalle api (Apis mellifera L.) utilizzando il nettare fornito dai fiori o le secrezioni di alcune piante e insetti. Negli ultimi anni sta crescendo l’interesse nei confronti degli antiossidanti naturali, presenti negli alimenti, utilizzati come protezione efficace contro il danno ossidativo. Tra questi, i composti fenolici presenti nei mieli (soprattutto flavonoidi) costituiscono uno dei gruppi più importanti per le loro proprietà funzionali e preventive. Tuttavia, l'attività antiossidante dei mieli varia notevolmente a seconda dell’origine botanica a causa dell’elevata diversità strutturale dei derivati polifenolici che le api, quando raccolgono il nettare o la melata trasferiscono dalla pianta al miele. Considerando quindi il crescente interesse commerciale per la produzione di mieli uniflorali dovuto all'attenzione dei consumatori per le loro proprietà salutistiche e le diverse caratteristiche organolettiche, abbiamo analizzato il contenuto totale di polifenoli (TPC), l’attività antiossidante (saggi DPPH e ABTS) e il colore (test spettrofotometrico e comparatore ottico) di diversi mieli associati alla loro origine botanica. Sono stati analizzati 123 mieli, 91 millefiori e 32 uniflorali tra cui: girasole (Helianthus annuus L.), robinia (Robinia pseudoacacia L.), castagno (Castanea sativa L.), coriandolo (Coriandrum sativum L.), tiglio (Tilia spp. L.) e melata. L’origine botanica dei campioni è stata testata mediante analisi melissopalinologica e la qualità dei mieli è stata verificata misurando l'umidità relativa e il tenore in idrossimetilfurfurale (HMF). I risultati ottenuti hanno mostrato notevoli differenze in termini di potere antiossidante e contenuto fenolico totale tra i diversi mieli oggetto di analisi, ed una buona correlazione tra il colore e l'origine botanica del miele. Questo studio contribuisce quindi a migliorare la conoscenza dei potenziali effetti benefici di questo alimento sulla salute e suggerisce come il colore del miele di qualità potrebbe essere utilizzato come parametro per una rapida identificazione del suo contenuto in antiossidanti

Geographical characterisation of multifloral honeys from the Marche region (Italy) according to their antioxidant activity and colour using a chemometric approach

Multifloral honeys produced in the Marche region (Italy) were analysed leading to the antioxidant and colour characterisation of this type of regional honeys: the antioxidant activity was determined measuring total phenolic content (TPC), and using ABTS and DPPH assays. The elaboration of data with multivariate analyses enabled differentiation of the geographical origin of honey samples, namely as coming from the Mid/Coastal Hilly or from the High Hilly/Submountain belt of the Marche region. The cluster analysis applied to a selection of samples divided honeys belonging to the Mid/Coastal Hilly belt into three groups showing low, medium and high antioxidant activity and in part located in different areas of the region. Finally, using data of unifloral honeys from the Marche region previously determined, it was possible to have an indication of the prevalent nectar contained in most of the multifloral honey samples harvested in 2012 in the Marche region