Amyloids are insoluble protein fibrillar aggregates. The importance of characterizing their aggregation has steadily increased because of their link to human diseases and material science ...applications. In particular, misfolding and aggregation of the Josephin domain of ataxin-3 is implicated in spinocerebellar ataxia-3. Infrared nanospectroscopy, simultaneously exploiting atomic force microscopy and infrared spectroscopy, can characterize at the nanoscale the conformational rearrangements of proteins during their aggregation. Here we demonstrate that we can individually characterize the oligomeric and fibrillar species formed along the amyloid aggregation. We describe their secondary structure, monitoring at the nanoscale an α-to-β transition, and couple these studies with an independent measurement of the evolution of their intrinsic stiffness. These results suggest that the aggregation of Josephin proceeds from the monomer state to the formation of spheroidal intermediates with a native structure. Only successively, these intermediates evolve into misfolded aggregates and into the final fibrils.
The widespread misuse of drugs has increased the number of multiresistant bacteria, and this means that tools that can rapidly detect and characterize bacterial response to antibiotics are much ...needed in the management of infections. Various techniques, such as the resazurin-reduction assays, the mycobacterial growth indicator tube or polymerase chain reaction-based methods, have been used to investigate bacterial metabolism and its response to drugs. However, many are relatively expensive or unable to distinguish between living and dead bacteria. Here we show that the fluctuations of highly sensitive atomic force microscope cantilevers can be used to detect low concentrations of bacteria, characterize their metabolism and quantitatively screen (within minutes) their response to antibiotics. We applied this methodology to Escherichia coli and Staphylococcus aureus, showing that live bacteria produced larger cantilever fluctuations than bacteria exposed to antibiotics. Our preliminary experiments suggest that the fluctuation is associated with bacterial metabolism.
Abstract High failure rates of femoropopliteal artery reconstruction are commonly attributed to complex 3D arterial deformations that occur with limb movement. The purpose of this study was to ...develop a method for accurate assessment of these deformations. Custom-made stainless-steel markers were deployed into 5 in situ cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were acquired with each limb in the straight and acutely bent states. Image segmentation and 3D reconstruction allowed comparison of the relative locations of each intra-arterial marker position for determination of the artery’s bending, torsion and axial compression. After imaging, each artery was excised for histological analysis using Verhoeff–Van Gieson staining. Femoropopliteal arteries deformed non-uniformly with highly localized deformations in the proximal superficial femoral artery, and between the adductor hiatus and distal popliteal artery. The largest bending (11±3–6±1 mm radius of curvature), twisting (28±9–77±27°/cm) and axial compression (19±10–30±8%) were registered at the adductor hiatus and the below knee popliteal artery. These deformations were 3.7, 19 and 2.5 fold more severe than values currently reported in the literature. Histology demonstrated a distinct sub-adventitial layer of longitudinally oriented elastin fibers with intimal thickening in the segments with the largest deformations. This endovascular intra-arterial marker technique can quantify the non-uniform 3D deformations of the femoropopliteal artery during knee flexion without disturbing surrounding structures. We demonstrate that 3D arterial bending, torsion and compression in the flexed lower limb are highly localized and are substantially more severe than previously reported.
•This paper is the first study of the atmospheric entry of grains made of mixed carbonatic composition.•Such compositions have never been considered in previous studies while they are gaining ...visibility as mineral phases associated to organic matter in Space.•The study shows that carbonates undergo total conversion to oxides at high altitude for most entry conditions but some carbonate survives for grazing scenarios.•These results are important in the context of organic matter delivery from Space to Earth.
Current models allow to reliably simulate mechanical and thermal phenomena associated with a micrometeor passage through the Earth’s atmosphere. However, these models have rarely been applied to materials other than those most common in meteorites, such as silicates and metals. A particular case that deserves attention is the one of micrograins made of minerals, in particular carbonates, which have been associated, in meteorites, with organic molecules. Carbonates are known for their decomposition in vacuum at moderate temperatures, and they might contribute to the thermal protection of organic matter. In this work, a model with non isothermal atmosphere, power balance, evaporation, ablation, radiation losses and stoichiometry, is proposed. This paper includes the very first calculations for meteoroids with a mixed carbonate composition. Results show that the carbonate fraction of these objects always go to zero at high altitudes except for grazing entries, where the reached temperature is lower and some carbonate remains unreacted. For all entry conditions, peculiar temperature curves are obtained due to the decomposition process. Furthermore, a significant impact of decomposition cooling on the temperature peak is observed for some grazing entry cases. Although specific solutions used in these calculations can be improved, this work sets a definite model and a basis for future research on sub-mm grains of relatively volatile minerals entering the Earth’s atmosphere.
Introduction
During the last decade, a growing digitalization allowed to implement technologies in daily life activities. Conversely, the increased use of technologies in general population, ...particularly in youths, facilitated the emergence of new web-based psychopathologies, including Pathological Internet use (PIU).
Objectives
Our study aims at investigating the relationship between PIU and boredom as well as loneliness dimensions in youths, by also focusing on the association with the main psychopathological symptomatology (i.e., depression, anxiety and stress).
Methods
A nationwide population-based cross-sectional case-control study was conducted by recruiting a sample of Italian young adults (aged 18-24), using a snowball sampling strategy. After data cleaning, only 1,643 participants were selected for analysis based on age and classified according to the presence/absence of PIU/non-PIU. Linear regression analyses as well as Pearson correlation analyses were conducted to check for possible associations and correlations between PIU and stress/anxiety/depression. Subsequently, mediation analyses regarding boredom and loneliness were conducted on these relationships.
Results
Participants were predominantly females (68.7%; n = 1,129). The mean age was 21.8 years (SD = 1.7), particularly ranging 20-24 years-old (88.5%; n = 1454). Around 41.7% (n = 685) of the sample declared previous psychological issues without a history of professional support (psychological and/or psychiatric), while 32.7% (n = 538) stated that they had an overt mental disorder and were currently receiving professional support. Mediation analysis demonstrated that both boredom and loneliness act as mediators in the association between PIU and depression.
Conclusions
Further studies are needed to evaluate how boredom and loneliness dimensions could be managed in order to alleviate the emergence of PIU in youths with clinically relevant depressive symptomatology.
Disclosure of Interest
None Declared
A variety of fundamental astrophysical science topics require the determination of very accurate photometric redshifts (photo-z). A wide plethora of methods have been developed, based either on ...template models fitting or on empirical explorations of the photometric parameter space. Machine-learning-based techniques are not explicitly dependent on the physical priors and able to produce accurate photo-z estimations within the photometric ranges derived from the spectroscopic training set. These estimates, however, are not easy to characterize in terms of a photo-z probability density function (PDF), due to the fact that the analytical relation mapping the photometric parameters on to the redshift space is virtually unknown. We present METAPHOR (Machine-learning Estimation Tool for Accurate PHOtometric Redshifts), a method designed to provide a reliable PDF of the error distribution for empirical techniques. The method is implemented as a modular workflow, whose internal engine for photo-z estimation makes use of the MLPQNA neural network (Multi Layer Perceptron with Quasi Newton learning rule), with the possibility to easily replace the specific machine-learning model chosen to predict photo-z. We present a summary of results on SDSS-DR9 galaxy data, used also to perform a direct comparison with PDFs obtained by the LE PHARE spectral energy distribution template fitting. We show that METAPHOR is capable to estimate the precision and reliability of photometric redshifts obtained with three different self-adaptive techniques, i.e. MLPQNA, Random Forest and the standard K-Nearest Neighbors models.
ABSTRACT
We study the nuclear (AGN) activity in the local Universe (z < 0.33) and its correlation with the host galaxy properties, derived from a Sloan Digital Sky Survey sample with spectroscopic ...star-formation rate (SFR) and stellar mass determination. To quantify the level of AGN activity we used the XMM-Newton Serendipitous Source Catalogue. Applying multiwavelength selection criteria (optical BPT-diagrams, X-ray/optical ratio etc), we found that 24 per cent of the detected sources are efficiently-accreting AGN with moderate-to-high X-ray luminosity, twice as likely to be hosted by star-forming galaxies than by quiescent ones. The distribution of the specific Black Hole accretion rate (λsBHAR) shows that nuclear activity in local, non-AGN dominated galaxies peaks at very low accretion rates (−4 ≲ log λsBHAR ≲ −3) in all stellar mass ranges. We observe systematically larger values of λsBHAR for galaxies with active star formation than for quiescent ones, and an increase of the mean λsBHAR with SFR for both star-forming and quiescent galaxies. These finding confirm the decrease in AGN activity with cosmic time and are consistent with a scenario where both star-formation and AGN activity are fuelled by a common gas reservoir.
The Multi Layer Perception with Quasi Newton Algorithm (MLPQNA) is a machine learning method that can be used to cope with regression and classification problems on complex and massive data sets. In ...this paper, we give a formal description of the method and present the results of its application to the evaluation of photometric redshifts for quasars. The data set used for the experiment was obtained by merging four different surveys (Sloan Digital Sky Survey, GALEX, UKIDSS, and WISE), thus covering a wide range of wavelengths from the UV to the mid-infrared. The method is able (1) to achieve a very high accuracy, (2) to drastically reduce the number of outliers and catastrophic objects, and (3) to discriminate among parameters (or features) on the basis of their significance, so that the number of features used for training and analysis can be optimized in order to reduce both the computational demands and the effects of degeneracy. The best experiment, which makes use of a selected combination of parameters drawn from the four surveys, leads, in terms of Delta z sub(norm) (i.e., (z sub(spec) - z sub(phot))/(1 + z sub(spec))), to an average of Delta z sub(norm) = 0.004, a standard deviation of sigma - 0.069, and a median absolute deviation, MAD = 0.02, over the whole redshift range (i.e., z sub(spec) < or =, slant 3.6), defined by the four-survey cross-matched spectroscopic sample. The fraction of catastrophic outliers, i.e., of objects with photo-z deviating more than 2sigma from the spectroscopic value, is <3%, leading to sigma = 0.035 after their removal, over the same redshift range. The method is made available to the community through the DAMEWARE Web application.
The protein kinase Syk is a key mediator of proximal B-cell receptor (BCR) signaling. Following antigen stimulation, Syk is recruited to the BCR and becomes activated by phosphorylation at Y352. ...Recently, Syk was found to be constitutively phosphorylated in several common B-cell lymphoma subtypes, indicating a role for antigen-independent Syk activation in the pathogenesis of these diseases. We now report that Syk is constitutively phosphorylated on the activating Y352 residue in chronic lymphocytic leukemia (CLL) B cells. To examine the effects of constitutive Syk activity on intracellular signaling and leukemic cell survival, we performed in vitro studies with the Syk inhibitor R406. Treatment with R406 induced leukemic cell apoptosis in the majority of investigated cases and affected the basal activity or expression of several pro-survival molecules regulated by Syk, including the Akt and extracellular signal-regulated (ERK) kinases, and the anti-apoptotic protein Mcl-1. In addition, R406 prevented the increase in leukemic cell viability induced by sustained BCR engagement and inhibited BCR-induced Akt activation and Mcl-1 upregulation. Collectively, these data identify Syk as a potential target for CLL treatment and suggest that inhibition of this kinase could provide a double therapeutic benefit by disrupting both antigen-dependent and antigen-independent signaling pathways that regulate leukemic cell survival.
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