The stratum corneum represents the first skin barrier against chemical and physical damage. These unique properties are based on its peculiar lipid composition with ceramides (CERs) as the main ...protagonists. In this study, the structural and chemical properties of the α-OH phytosphingosine AP CER class have been investigated. α-OH CERs are present in the stratum corneum in their d-forms; however, in most model systems the diastereomer mixture with the synthetically produced l-form is used. The d-form is well-known to form a hydrogen bonding network that helps to reduce the permeability of the lipid matrix, while the l-form does not show any hydrogen bonding network formation. In this paper, 2D (monolayers) and 3D (aqueous dispersions) models have been used to thoroughly study the physical–chemical behaviors of CERAP diastereomers taking into account how the symmetry of the chain pattern influences the behavior of the molecules. The chains of both diastereomers arrange in an oblique unit cell, but only the d-CERAP forms a supramolecular lattice (subgel phase) in both model systems. Interestingly, the chain pattern does not play any role in structure formation since the hydrogen bonding network dictates the packing properties. The 1:1 mixture of the diastereomers phase separates into two domains: one is composed of practically pure d-form and the other one is composed of a mixture of the l-form with a certain amount of d-form molecules.
Anthocyanins are much more than flavylium cation. At least four other species in moderately acidic solutions are formed constituting a pH reversible network of chemical reactions. The study of this ...network is an indispensable tool to rationalize the colour as well as the reactivity of these molecules. The network of anthocyanins was revisited and the one of related compounds, such as vitisins, described in detail. The colour given by anthocyanins is function of their concentration due to self-aggregation as well as by the possibility of co-pigmentation with other wine components. These phenomena can only be fully understood if the thermodynamic and kinetics of anthocyanins and related compounds are known. In aged red wines, vitisins nicely illustrate the evolution of anthocyanins. These compounds result from the chemical reaction of anthocyanins with other wine components and are very resistant to the hydration lacking the colourless hemiketals formation. This indicates that less colorant is necessary to confer colour to the wine and also explains the colour change from the red-violet in young wines to the red-orange observed in aged wines.
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Upwelling systems are characterised by an intense primary biomass production in the surface (warmest) water after the outcrop of the bottom (coldest) water, which is rich in nutrients. Although it is ...known that the microbial assemblage plays an important role in the food chain of marine systems and that the upwelling systems that occur in southwest Brazil drive the complex dynamics of the food chain, little is known about the microbial composition present in this region.
We carried out a molecular survey based on SSU rRNA gene from the three domains of the phylogenetic tree of life present in a tropical upwelling region (Arraial do Cabo, Rio de Janeiro, Brazil). The aim was to analyse the horizontal and vertical variations of the microbial composition in two geographically close areas influenced by anthropogenic activity (sewage disposal/port activity) and upwelling phenomena, respectively. A lower estimated diversity of microorganisms of the three domains of the phylogenetic tree of life was found in the water of the area influenced by anthropogenic activity compared to the area influenced by upwelling phenomena. We observed a heterogenic distribution of the relative abundance of taxonomic groups, especially in the Archaea and Eukarya domains. The bacterial community was dominated by Proteobacteria, Cyanobacteria and Bacteroidetes phyla, whereas the microeukaryotic community was dominated by Metazoa, Fungi, Alveolata and Stramenopile. The estimated archaeal diversity was the lowest of the three domains and was dominated by uncharacterised marine Crenarchaeota that were most closely related to Marine Group I.
The variety of conditions and the presence of different microbial assemblages indicated that the area of Arraial do Cabo can be used as a model for detailed studies that contemplate the correlation between pollution-indicating parameters and the depletion of microbial diversity in areas close to anthropogenic activity; functional roles and geochemical processes; phylogeny of the uncharacterised diversity; and seasonal variations of the microbial assemblages.
In preparation for the ESA/JAXA BepiColombo mission to Mercury, thematic working groups had been established for coordinating the activities within the BepiColombo Science Working Team in specific ...fields. Here we describe the scientific goals of the Geodesy and Geophysics Working Group (GGWG) that aims at addressing fundamental questions regarding Mercury’s internal structure and evolution. This multidisciplinary investigation will also test the gravity laws by using the planet Mercury as a proof mass. The instruments on the Mercury Planetary Orbiter (MPO), which are devoted to accomplishing the GGWG science objectives, include the BepiColombo Laser Altimeter (BELA), the Mercury orbiter radio science experiment (MORE), and the MPO magnetometer (MPO-MAG). The onboard Italian spring accelerometer (ISA) will greatly aid the orbit reconstruction needed by the gravity investigation and laser altimetry. We report the current knowledge on the geophysics, geodesy, and evolution of Mercury after the successful NASA mission MESSENGER and set the prospects for the BepiColombo science investigations based on the latest findings on Mercury’s interior. The MPO spacecraft of the BepiColombo mission will provide extremely accurate measurements of Mercury’s topography, gravity, and magnetic field, extending and improving MESSENGER data coverage, in particular in the southern hemisphere. Furthermore, the dual-spacecraft configuration of the BepiColombo mission with the
Mio
spacecraft at higher altitudes than the MPO spacecraft will be fundamental for decoupling the internal and external contributions of Mercury’s magnetic field. Thanks to the synergy between the geophysical instrument suite and to the complementary instruments dedicated to the investigations on Mercury’s surface, composition, and environment, the BepiColombo mission is poised to advance our understanding of the interior and evolution of the innermost planet of the solar system.
Purpose This study explores how excellence models can leverage digital transformation on the path to sustainable development in organisations. Design/methodology/approach A survey was used to study ...the different facets of digital capabilities and their impact on sustainable development success of organisations holding an external recognition from the European Foundation for Quality Management (EFQM). Partial Least Squares structural equation modelling (PLS-SEM) combined with Necessary Condition Analysis (NCA) were used to analyse data. Findings Internalising excellence practices is decisive in mediating effective digital capabilities to achieve sustainable development. To achieve high levels of sustainable development success, organisations must achieve high levels of excellence practices internalisation, which are much more important than the excellence model external recognition. Research limitations/implications This study addresses essential issues with theoretical and practical value but is limited to a sample of organisations with EFQM recognition in two countries. Future studies should address different organisations and cultural environments. Practical implications The findings are relevant for organisations facing digital transformation and sustainable development challenges. They are essential for managers leveraging digital capabilities to capitalise on practices and processes and achieve Sustainable Development Goals. Organisations can benefit from a multidimensional approach to digital capabilities when struggling against external challenges. Originality/value This study closes a research gap regarding the impact of digital capabilities on sustainable development success. It is the first empirical study to combine sufficiency and necessity conditions analyses to explore the mediating role of excellence practices internalisation and one of the first to address digital capabilities from a multidimensional perspective.
ABSTRACT
We present a supervised machine learning methodology to classify stellar populations in the Local Group dwarf-irregular galaxy NGC 6822. Near-IR colours (J − H, H − K, and J − K), K-band ...magnitudes and far-IR surface brightness (at 70 and 160 $\mu$m) measured from Spitzer and Herschel images are the features used to train a Probabilistic Random Forest (PRF) classifier. Point-sources are classified into eight target classes: young stellar objects (YSOs), oxygen- and carbon-rich asymptotic giant branch stars, red giant branch and red supergiant stars, active galactic nuclei, massive main-sequence stars, and Galactic foreground stars. The PRF identifies sources with an accuracy of ∼ 90 per cent across all target classes rising to ∼96 per cent for YSOs. We confirm the nature of 125 out of 277 literature YSO candidates with sufficient feature information, and identify 199 new YSOs and candidates. Whilst these are mostly located in known star-forming regions, we have also identified new star formation sites. These YSOs have mass estimates between ∼15 and 50 M⊙, representing the most massive YSO population in NGC 6822. Another 82 out of 277 literature candidates are definitively classified as non-YSOs by the PRF analysis. We characterize the star formation environment by comparing the spatial distribution of YSOs to those of gas and dust using archival images. We also explore the potential of using (unsupervised) t-distributed stochastic neighbour embedding maps for the identification of the same stellar population classified by the PRF.
Emerging evidence supports combining immune checkpoint inhibitors (ICIs) with conventional or targeted therapies to enhance ICI antitumour activity and broaden the spectrum of patients who respond to ...ICIs. Here, we present the safety and preliminary efficacy of ramucirumab, an anti-VEGFR2 IgG1, plus durvalumab, an anti–PD-L1 IgG1, in previously treated patients with advanced non–small-cell lung cancer (NSCLC), gastric/gastro-oesophageal junction adenocarcinoma (gastric/GEJ), or hepatocellular carcinoma (HCC).
A 25-centre, phase Ia/b single-arm, non-randomised, multi-cohort study was undertaken in patients with advanced/metastatic disease, Eastern Cooperative Oncology Group performance status, 0–1, progression on prior therapy, no prior ramucirumab or immunotherapy and any PD-L1 status. Patients received ramucirumab (10 mg/kg) plus durvalumab (1125 mg) intravenously Q3W (NSCLC), or ramucirumab (8 mg/kg) plus durvalumab (750 mg) Q2W (gastric/GEJ, HCC).
Phase Ia treatment was found safe for phase Ib expansion; final enrolment was NSCLC (n = 28), gastric/GEJ (n = 29), HCC (n = 28). Grade ≥3 treatment–related adverse events occurred in 32.1%, 37.9% and 42.9% of patients, respectively. The most common were fatigue (35.7%), hypertension (34.5%) and diarrhoea (28.6%), respectively. Two patients died owing to an adverse event; one was treatment-related (hepatitis acute, HCC cohort). Objective response rate was 11% for NSCLC and HCC and 21% for gastric/GEJ. Median progression-free survival and overall survival were, respectively, 2.7 and 11 months in NSCLC; 2.6 and 12.4 months in gastric/GEJ; 4.4 and 10.7 months in HCC, with more prolonged survival in patients with high PD-L1 expression.
Ramucirumab/durvalumab exhibited manageable safety. The combination showed antitumour activity in all cohorts, particularly in patients with high PD-L1 expression.
•The clinical efficacy of immune checkpoint inhibitor monotherapy appears limited to a subset of patients.•The combination of ramucirumab with durvalumab was well tolerated by patients.•Blockade of both VEGFR2 and PD-L1 pathways can potentially increase clinical benefit.•Dual blockade might expand the subset of patients with non–small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma and hepatocellular carcinoma responding to an immune checkpoint inhibitor.
ABSTRACT
We present a supervised machine learning classification of stellar populations in the Local Group spiral galaxy M 33. The Probabilistic Random Forest (PRF) methodology, previously applied to ...populations in NGC 6822, utilizes both near and far-IR classification features. It classifies sources into nine target classes: young stellar objects (YSOs), oxygen, and carbon-rich asymptotic giant branch stars, red giant branch, and red super-giant stars, active galactic nuclei, blue stars (e.g. O-, B-, and A-type main sequence stars), Wolf–Rayet stars, and Galactic foreground stars. Across 100 classification runs the PRF classified 162 746 sources with an average estimated accuracy of ∼86 per cent, based on confusion matrices. We identified 4985 YSOs across the disc of M 33, applying a density-based clustering analysis to identify 68 star forming regions (SFRs) primarily in the galaxy’s spiral arms. SFR counterparts to known H ii regions were recovered with ∼91 per cent of SFRs spatially coincident with giant molecular clouds identified in the literature. Using photometric measurements, as well as SFRs in NGC 6822 with an established evolutionary sequence as a benchmark, we employed a novel approach combining ratios of Hα/24 μm and 250 μm/500 μm to estimate the relative evolutionary status of all M 33 SFRs. Masses were estimated for each YSO ranging from 6–27M⊙. Using these masses, we estimate star formation rates based on direct YSO counts of 0.63M⊙ yr−1 in M 33’s SFRs, 0.79 ± 0.16M⊙ yr−1 in its centre and 1.42 ± 0.16M⊙ yr−1 globally.
Objectives
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal‐to‐bilateral tonic–clonic seizures ...(FBTCS) are a major risk factor, and centrally‐mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post‐convulsive central apnea (PCCA).
Methods
Seventy‐three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high‐resolution T1‐weighted anatomic and multi‐shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG.
Results
Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort.
Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non‐apnea FBTCpos group (p = 0.004).
Significance
Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.
Abstract
The VISTA near-infrared YJK
s survey of the Magellanic System (VMC) is collecting deep K
s-band time-series photometry of pulsating stars hosted by the two Magellanic Clouds and their ...connecting bridge. Here, we present Y, J, K
s light curves for a sample of 717 Small Magellanic Cloud (SMC) Classical Cepheids (CCs). These data, complemented with our previous results and V magnitude from literature, allowed us to construct a variety of period–luminosity and period–Wesenheit relationships, valid for Fundamental, First and Second Overtone pulsators. These relations provide accurate individual distances to CCs in the SMC over an area of more than 40 deg2. Adopting literature relations, we estimated ages and metallicities for the majority of the investigated pulsators, finding that (i) the age distribution is bimodal, with two peaks at 120 ± 10 and 220 ± 10 Myr; (i) the more metal-rich CCs appear to be located closer to the centre of the galaxy. Our results show that the three-dimensional distribution of the CCs in the SMC is not planar but heavily elongated for more than 25–30 kpc approximately in the east/north-east towards south-west direction. The young and old CCs in the SMC show a different geometric distribution. Our data support the current theoretical scenario predicting a close encounter or a direct collision between the Clouds some 200 Myr ago and confirm the presence of a Counter-Bridge predicted by some models. The high-precision three-dimensional distribution of young stars presented in this paper provides a new test bed for future models exploring the formation and evolution of the Magellanic System.
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