The origin of the high-velocity cloud complex C

High-velocity clouds consist of cold gas that appears to be raining down from the halo to the disc of the Milky Way. Over the past fifty years, two competing scenarios have attributed their origin either to gas accretion from outside the Galaxy or to circulation of gas from the Galactic disc powered by supernova feedback (galactic fountain). Here we show that both mechanisms are simultaneously at work. We use a new galactic fountain model combined with high-resolution hydrodynamical simulations. We focus on the prototypical cloud complex C and show that it was produced by an explosion that occurred in the Cygnus-Outer spiral arm about 150 million years ago. The ejected material has triggered the condensation of a large portion of the circumgalactic medium and caused its subsequent accretion onto the disc. This fountain-driven cooling of the lower Galactic corona provides the low-metallicity gas required by chemical evolution models of the Milky Way's disc.Comment: 6 pages, 4 figures, 1 table; accepted by MNRA

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

The angular momentum of disc galaxies at z=1

We investigate the relation between stellar mass and specific stellar angular momentum, or `Fall relation', for a sample of 17 isolated, regularly rotating disc galaxies at z=1. All galaxies have a) rotation curves determined from Halpha emission-line data; b) HST imaging in optical and infrared filters; c) robust determinations of their stellar masses. We use HST images in f814w and f160w filters, roughly corresponding to rest-frames B and I bands, to extract surface brightness profiles for our systems. We robustly bracket the specific angular momentum by assuming that rotation curves beyond the outermost Halpha rotation point stay either flat or follow a Keplerian fall-off. By comparing our measurements with those determined for disc galaxies in the local Universe, we find no evolution in the Fall relation in the redshift range 0<z<1, regardless of the band used and despite the uncertainties in the stellar rotation curves at large radii. This result holds unless stellar masses at z=1 are systematically underestimated by more than 50%. Our findings are compatible with expectations based on a LCDM cosmological framework and support a scenario where both the stellar Tully-Fisher and mass-size relations for spirals do not evolve significantly in this redshift range.Comment: 11 pages, 4 figures, 1 table. Accepted by A&

Clinical presentation of celiac disease and diagnosis accuracy in a single-center european pediatric cohort over 10 years

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD

Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein.

BACKGROUND: Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals. RESULTS: We show the identification of a Lactobacillus plantarum LM3 cell surface protein (48 kDa), which specifically binds to human fibronectin (Fn), an extracellular matrix protein. By means of mass spectrometric analysis this protein was identified as the product of the L. plantarum enoA1 gene, coding the EnoA1 alfa-enolase. Surface localization of EnoA1 was proved by immune electron microscopy. In the mutant strain LM3-CC1, carrying the enoA1 null mutation, the 48 kDa adhesin was not anymore detectable neither by anti-enolase Western blot nor by Fn-overlay immunoblotting assay. Moreover, by an adhesion assay we show that LM3-CC1 cells bind to fibronectin-coated surfaces less efficiently than wild type cells, thus demonstrating the significance of the surface displaced EnoA1 protein for the L. plantarum LM3 adhesion to fibronectin. CONCLUSION: Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. We demonstrated the involvement of the L. plantarum Eno A1 alfa-enolase in Fn-binding, by studying LM3 and LM3-CC1 surface proteins. Isolation of LM3-CC1 strain was possible for the presence of expressed enoA2 gene in the L. plantarum genome, giving the possibility, for the first time to our knowledge, to quantitatively compare adhesion of wild type and mutant strain, and to assess doubtless the role of L. plantarum Eno A1 as a fibronectin binding protein

Predictive factors for hepatocellular carcinoma recurrence after curative treatments

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm worldwide. Recurrence of HCC after resection or loco-regional therapies represents an important clinical issue as it affects up to 70% of patients. This can be divided into early or late, if it occurs within or after 24 months after treatment, respectively. While the predictive factors for early recurrence are mainly related to tumour biology (local invasion and intrahepatic metastases), late recurrences are mainly related to de novo tumour formation. Thus, it is important to recognize these factors prior to any treatment in each patient, in order to optimize the treatment strategy and follow-up after treatment. The aim of this review is to summarize the current evidence available regarding predictive factors for the recurrence of HCC, according to the different therapeutic strategies available. In particular, we will discuss the role of new ultrasound-based techniques and biological features, such as tumor-related and circulating biomarkers, in predicting HCC recurrence. Recent advances in imaging-related parameters in computed-tomography scans and magnetic resonance imaging will also be discussed

ADVANCED DEEP LEARNING COMPARISONS FOR NON-INVASIVE TUNNEL LINING ASSESSMENT FROM GROUND PENETRATING RADAR PROFILES

Innovative, automated, and non-invasive techniques have been developed by scientific community to indirectly assess structural conditions and support the decision-making process for a worthwhile maintenance schedule. Nowadays, machine learning tools are in the spotlight because of their outstanding capabilities to deal with data coming from even heterogeneous sources and their ability to extract information from the structural systems, providing highly effective, reliable, and efficient damage classification tools. In the current study, a supervised multi-level damage classification strategy has been developed regarding Ground Penetrating Radar (GPR) profiles for the assessment of tunnel lining conditions. In previous research, the authors firstly considered a convolutional neural network (CNN), adopting the quite popular ResNet-50, initialized through transfer learning. In the present work, further enhancements have been attempted by adopting two configurations of the newest state-of-art advanced neural architectures: the neural transformers. The foremost is the original Vision Transformer (ViT), whose core is an encoder entirely based on the innovative self-attention mechanism and does not rely on convolution at all. The second is an improvement of ViT which merges convolution and self-attention, the Compact Convolution Transformer (CCT). In conclusion, a critical discussion of the different pros and cons of adopting the above-mentioned different architectures is finally provided, highlighting the actual powerfulness of these technologies in the future civil engineering paradigm nevertheless

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life

Skeletonized internal thoracic artery harvesting reduces chest wall dysesthesia after coronary bypass surgery

ObjectiveA pain syndrome related to intercostal nerve injury during internal thoracic artery harvesting causes significant morbidity after coronary bypass surgery. We hypothesized that its incidence and severity might be reduced by using skeletonized internal thoracic artery harvesting rather than pedicled harvesting.MethodsIn a prospective double-blind clinical trial, 41 patients undergoing coronary bypass were randomized to receive either unilateral pedicled or skeletonized internal thoracic artery harvesting. Patients were assessed 7 (early) and 21 (late) weeks postoperatively with reproducible sensory stimuli used to detect chest wall sensory deficits (dysesthesia) and with a pain questionnaire used to assess neuropathic pain.ResultsAt 7 weeks postoperatively, the area of harvest dysesthesia (percentage of the chest) in the skeletonized group (n = 21) was less (median, 0%; interquartile range, 0–0) than in the pedicled group (n = 20) (2.8% [0–13], P = .005). The incidence of harvest dysesthesia at 7 weeks was 14% in the skeletonized group versus 50% in the pedicled group (P = .02). These differences were not sustained at 21 weeks, as the median area of harvest dysesthesia in both groups was 0% (P = .89) and the incidence was 24% and 25% in the skeletonized and pedicled groups, respectively (P = 1.0). The incidence of neuropathic pain in the skeletonized group compared with the pedicled group was 5% versus 10% (P = .6) at 7 weeks and 0% versus 0% (P = 1.0) at 21 weeks.ConclusionsCompared with pedicled harvesting, skeletonized harvesting of the internal thoracic artery provides a short-term reduction in the extent and incidence of chest wall dysesthesia after coronary bypass, consistent with reduced intercostal nerve injury and therefore the reduced potential for neuropathic chest pain

Shaken, not blown: the gentle baryonic feedback of nearby starburst dwarf galaxies

Baryonic feedback is expected to play a key role in regulating the star formation of low-mass galaxies by producing galaxy-scale winds associated with mass-loading factors $\beta\!\sim\!1\!-\!50$. We have tested this prediction using a sample of 19 nearby systems with stellar masses $10^7\!<\!M_\star/{\rm M}_{\odot}\!<\!10^{10}$, mostly lying above the main sequence of star-forming galaxies. We used MUSE@VLT optical integral field spectroscopy to study the warm ionised gas kinematics of these galaxies via a detailed modelling of their H$\alpha$ emission line. The ionised gas is characterised by irregular velocity fields, indicating the presence of non-circular motions of a few tens of km/s within galaxy discs, but with intrinsic velocity dispersion of $40$-$60$ km/s that are only marginally larger than those measured in main-sequence galaxies. Galactic winds, defined as gas at velocities larger than the galaxy escape speed, encompass only a few percent of the observed fluxes. Mass outflow rates and loading factors are strongly dependent on $M_\star$, star formation rate (SFR), SFR surface density and specific SFR. For $M_\star$ of $10^8$ M$_\odot$ we find $\beta\simeq0.02$, which is more than two orders of magnitude smaller than the values predicted by theoretical models of galaxy evolution. In our galaxy sample, baryonic feedback stimulates a gentle gas cycle rather than causing a large-scale blow out.Comment: 20 pages, 11 figures, submitted to A&A. Comments are welcome