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Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree Π_X of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock.

AimsTo assess visual field (VF) pseudoprogression related to face mask use.MethodsWe reviewed a total of 307 VFs performed with a face mask (FPP2/KN95 or surgical masks) and compared them with prior VFs, performed before the pandemic. VFs with suspected pseudoprogression due to mask artefacts (VF test 1) were repeated with a surgical mask and an adhesive tape on its superior border (VF test 2) to distinguish from true VF loss. Several parameters including reliability indices, test duration, VF index (VFI), mean defect (MD) and pattern deviation probability plots were compared among last pre-COVID VFs, VF tests 1 and VF tests 2, using the Wilcoxon signed-rank test.ResultsWe identified 18 VFs with suspected progression artefact due to masks (5.8%). In all of them, the median VFI and MD significantly improved after fitting the superior border of the mask, showing no significant differences with pre-COVID tests. The median fixation losses were significantly higher when wearing the unfitted mask (13% vs 6%,p=0.047). The inferior hemifield was the most affected, either as a new scotoma or as an enlargement of a prior defect.ConclusionUnfitted masks can simulate VF progression in around 6% of cases, mainly in the inferior hemifield, and increase significantly the rate of fixation losses. A similar rate of artefacts was observed using FPP2/KN95 or surgical masks. The use of a surgical mask with an adhesive tape covering the superior border may reduce mask-related artefacts, although concomitant progression cannot be ruled out in all cases.

The cytoskeletal protein vimentin plays a key role in positioning of organelles within the cytosol and has been linked to the regulation of numerous cellular processes including autophagy, however, how vimentin regulates autophagy remains relatively unexplored. Here we report that inhibition of vimentin using the steroidal lactone Withaferin A (WFA) causes vimentin to aggregate, and this is associated with the relocalisation of organelles including autophagosomes and lysosomes from the cytosol to a juxtanuclear location. Vimentin inhibition causes autophagosomes to accumulate, and we demonstrate this results from modulation of mechanistic target of rapamycin (mTORC1) activity, and disruption of autophagosome-lysosome fusion. We suggest that vimentin plays a physiological role in autophagosome and lysosome positioning, thus identifying vimentin as a key factor in the regulation of mTORC1 and autophagy.

Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immunosuppressed and exacerbations of pre-existing pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Many of these conditions can place significant economic costs upon healthcare infrastructure. There is currently no licensed vaccine for rhinovirus, as the large variety of rhinovirus serotypes has posed significant challenges for research. In this review, we discuss current knowledge around antiviral drugs and small molecule inhibitors of rhinovirus infection, as well as antiviral host defense peptides as exciting prospects to approach the development of novel therapeutics which target human rhinovirus.

Background: File fracture during root canal treatment in endodontics is a major concern for clinicians. The strength of the file is strongly dependent on its geometry, material, and working conditions; finite element simulations are used to understand these failure mechanisms. One limitation of the models used for these simulations is the approximate geometric representation typically obtained by rotating and scaling a specific cross-section shape along the file length. Given the influence of file geometry on file strength, a more realistic representation based on the manufacturing method is needed. Methods: A computerized method was developed to generate the file geometry by simulating the flute grinding manufacturing process. This method generates the 3D geometry of the file starting from a blank and reproducing the motions of the file and grinding wheel. Results: The cross-section of the resulting geometry does not involve simple rotation and scaling but changes from the shank to the tip. The tilt angle of the grinding wheel affects the final geometry, thus altering the convexity of the cross-section. Several other parameters, such as the pitch and the radius of the grinding disc tip, impact the final geometry. Conclusions: The proposed computational method allows for the generation of endodontic file geometries that match those produced via the actual flute grinding method. This tool may help researchers and tool designers in the preparation of finite element models to assess the strength of realistic files.

In this article, the effects of cross-section and pitch on the mechanical response of NiTi endodontic files is studied by means of finite element analyses. The study was conducted over a set of eight endodontic rotary files, whose geometry was obtained from combinations of two cross-sections (square and triangular) and four pitches. Each file was subjected to bending and torsional analyses, simulating the testing conditions indicated in the ISO 3630 Standard, in order to assess their stiffness and mechanical strength. The results indicate that endodontic files with a square cross-section have double the stiffness of those with triangular cross-sections, both in terms of bending and torsion. For both loading modes, endodontic files with a triangular cross-section can undergo larger deformations before overload failure than those with a square cross-section: up to 20% more in bending and 40% in torsion. Moreover, under equivalent boundary conditions, endodontic files with triangular cross-sections present a higher fatigue life than those with square cross-sections: up to more than 300% higher for small pitches. The effect of pitch on the stiffness and strength of the file is smaller than that of the cross-section shape, but smaller pitches could be beneficial when using a triangular cross-section, as they increase the bending flexibility, fatigue life, and torsion stiffness. These results suggest a clinical recommendation for the use of files with a triangular-shaped cross-section and a small pitch in order to minimize ledging and maximize fatigue life. Finally, in this study, we reveal the sensitivity of the orientation of files with respect to the bending direction, which must be taken into account when designing, reporting, and interpreting test results under such loading conditions.

Endodontic rotary file geometries are often obtained using computed tomography (CT) scans, which produce 3D models comprising point clouds and triangulated surfaces. Despite being widely used, this approach has significant limitations; scanned geometries may deviate from the theoretical design due to physical deformation during manipulation, inaccuracies due to the scanner resolution, and the non-parametric nature of the resulting mesh, preventing design modification or parameter extraction. This study proposes a methodology to overcome these limitations by recognizing and reconstructing the scanned geometry. This process involves correcting deformation caused by flexion, applying filtering techniques to minimize scan-induced noise, and identifying key geometric parameters. This enables the generation of a manipulable and accurate CAD model which not only preserves the original design intention but also allows for parametric modifications and advanced finite element analysis. The proposed method bridges the gap between real geometry acquisition and design-based simulation, providing a powerful tool for endodontic instrument evaluation and optimization.

Human rhinoviruses (HRV) are the most common cause of viral respiratory tract infections. While normally mild and self-limiting in healthy adults, HRV infections are associated with bronchiolitis in infants, pneumonia in immunocompromised patients, and exacerbations of asthma and COPD. The human cathelicidin LL-37 is a host defense peptide (HDP) with broad immunomodulatory and antimicrobial activities that has direct antiviral effects against HRV. However, LL-37 is known to be susceptible to the enzymatic activity of peptidyl arginine deiminases (PAD), and exposure of the peptide to these enzymes results in the conversion of positively charged arginines to neutral citrullines (citrullination). Here, we demonstrate that citrullination of LL-37 reduced its direct antiviral activity against HRV. Furthermore, while the anti-rhinovirus activity of LL-37 results in dampened epithelial cell inflammatory responses, citrullination of the peptide, and a loss in antiviral activity, ameliorates this effect. This study also demonstrates that HRV infection upregulates PAD2 protein expression, and increases levels of protein citrullination, including histone H3, in human bronchial epithelial cells. Increased gene expression and HDP citrullination during infection may represent a novel viral evasion mechanism, likely applicable to a wide range of pathogens, and should therefore be considered in the design of therapeutic peptide derivatives.

Automation of wrist rotations in upper limb prostheses allows simplification of the human–machine interface, reducing the user’s mental load and avoiding compensatory movements. This study explored the possibility of predicting wrist rotations in pick-and-place tasks based on kinematic information from the other arm joints. To do this, the position and orientation of the hand, forearm, arm, and back were recorded from five subjects during transport of a cylindrical and a spherical object between four different locations on a vertical shelf. The rotation angles in the arm joints were obtained from the records and used to train feed-forward neural networks (FFNNs) and time-delay neural networks (TDNNs) in order to predict wrist rotations (flexion/extension, abduction/adduction, and pronation/supination) based on the angles at the elbow and shoulder. Correlation coefficients between actual and predicted angles of 0.88 for the FFNN and 0.94 for the TDNN were obtained. These correlations improved when object information was added to the network or when it was trained separately for each object (0.94 for the FFNN, 0.96 for the TDNN). Similarly, it improved when the network was trained specifically for each subject. These results suggest that it would be feasible to reduce compensatory movements in prosthetic hands for specific tasks by using motorized wrists and automating their rotation based on kinematic information obtained with sensors appropriately positioned in the prosthesis and the subject’s body.

The HIV regulatory protein Tat enhances viral transcription and also modifies host gene expression, affecting cell functions like cell cycle and apoptosis. Residual expression of Tat protein is detected in blood and other tissues even under antiretroviral treatment. Cohort studies have indicated that, despite virologic suppression, people with HIV (PWH) are at increased risk of comorbidities linked to chronic inflammation, accelerated immune ageing, and cellular senescence, sometimes associated with abnormal genomic methylation patterns. We analysed whether Tat influences DNA methylation and subsequently impacts the transcriptional signature, contributing to inflammation and accelerated ageing. We transfected Jurkat cells with full-length Tat (Tat101), Tat's first exon (Tat72), or an empty vector (TetOFF). We assessed DNA methylation modifications via the Infinium MethylationEPIC array, and we evaluated transcriptomic alterations through RNA-Seq. Methylation levels in gene promoters or body regions were correlated to their expression data, and subsequently, we performed an overrepresentation analysis to identify the biological terms containing differentially methylated and expressed genes. Tat101 expression caused significant hyper- and hypomethylation changes at individual CpG sites, resulting in slightly global DNA hypermethylation. Methylation changes at gene promoters and bodies resulted in altered gene expression, specifically regulating gene transcription in 5.1% of differentially expressed genes (DEGs) in Tat101- expressing cells. In contrast, Tat72 had a minimal impact on this epigenetic process. The observed differentially methylated and expressed genes were involved in inflammatory responses, lipid antigen presentation, and apoptosis. Tat expression in HIV infection may constitute a key epigenetic modelling actor that contributes to HIV pathogenesis and chronic inflammation. Clinical interventions targeting Tat blockade may reduce chronic inflammation and cellular senescence related to HIV infection comorbidities.