137262 research outputs found
Sort by
FGF Signaling Promotes Lysosome Biogenesis in Chondrocytes via the Mannose Phosphate Receptor Pathway
The mannose 6-phosphate (M6P) pathway is critical for lysosome biogenesis, facilitating the trafficking of hydrolases to lysosomes to ensure cellular degradative capacity. Fibroblast Growth Factor (FGF) signaling, a key regulator of skeletogenesis, has been linked to the autophagy-lysosomal pathway in chondrocytes, but its role in lysosome biogenesis remains poorly characterized. Here, using mass spectrometry, lysosome immune-purification, and functional assays, we reveal that RCS (Swarm rat chondrosarcoma cells) lacking FGF receptors 3 and 4 exhibit dysregulations of the M6P pathway, resulting in hypersecretion of lysosomal enzymes and impaired lysosomal function. We found that FGF receptors control the expression of M6P receptor genes in response to FGF stimulation and during cell cycle via the activation of the transcription factors TFEB and TFE3. Notably, restoring M6P pathway—either through gene expression or activation of TFEB—significantly rescues lysosomal defects in FGFR3;4-deficient RCS. These findings uncover a novel mechanism by which FGF signaling regulates lysosomal function, offering insights into the control of chondrocyte catabolism and the understanding of FGF-related human diseases
Effect of fire propagation modelling on structural elements temperature of steel racks
Automated Rack-Supported Warehouses (ARSWs) are a particular type of steel racks that combine the structural efficiency of steel construction with automated machines for handling stored products. This work addressed the fire development in ARSW, by investigating the fire modelling which can be used in a multi-depth ARSW structure, by adopting zone models, and Computational Fluid Dynamics (CFD) ones. Since the traveling fire plays a key role in these peculiar structures, a simplified “multi-cells” fire model that allows vertical and horizontal propagation, is proposed. Starting from the results of an extensive experimental campaign, available in the literature, conducted on steel racks, criteria to evaluate the vertical and horizontal propagation times are provided. Finally, the criteria of the simplified fire model were also compared with the results of advanced CFD analyses, in which the traveling fire was naturally considered, showing a good agreement. This proposed “multi-cells” zone model provides a useful tool for both design and assessment of the fire behaviour of ARSW structures
Mechanical Transitions in Crystals: The Low-Temperature Thermosalient Transition of a Mesogenic Polyphenyl
Thermosalient transitions are a subset of single-crystal-to-single-crystal (SCSC) transitions, in which the change of lattice parameters is highly anisotropic and very fast. As a result, crystals at the transition undergo macroscopic dynamical effects (hopping, jumping, and shattering). These transitions feature a conversion of heat to mechanical energy that can be exploited in the realization of advanced materials. Most thermosalient transitions are observed at temperatures higher than room temperature. Examples of low-temperature thermosalient transitions are rare. We describe a new example of a low-temperature thermosalient transition in a sexiphenyl compound. At about −40 °C, the parent single crystal (phase I) shatters into single crystal fragments of the new phase (phase II). The two phases have been studied by single-crystal X-ray analysis using a synchrotron source, variable-temperature Raman spectroscopy, and computational analysis of lattice normal vibration modes. A mechanism of the transition is proposed. We confirm colossal thermal expansion coefficients and supercells as reliable features of thermosalient transitions and add as a third feature a low-frequency principal optical vibration of the crystal lattice prompting the transition. Based on this, a roadmap for the automated prediction of thermosalient transitions in molecular crystals is also outlined
Assessing Walking Accessibility: A GIS-Based Analysis of Postal Services in the City of Naples
The current patterns of rapid urbanization pose significant challenges to social and economic inclusion. The planning of local services within urban environment is crucial in addressing issues of accessibility. The assessment and resolution of shortcomings depends on holistic assessment of disparities in accessibility.
This paper examines the accessibility of population to local services, with a particular focus on postal services in the city of Naples. In the Italian context, as in many other nations, national posts provide a broad range of essential logistical, financial and social services, making their accessibility a key factor in urban inclusion. In the case of Poste Italiane, in line with obligations under European and national law, the company explicitly states that the strategic positioning of its offices is essential to effective community service.
The study develops a modified Two Step Floating Catchment Area (2SFCA) methodology to measure the levels of accessibility to post offices during both morning and afternoon hours. The research aims to identify spatial disparities in service accessibility and to provide insights into improving urban planning and service distribution, particularly for more vulnerable population groups. The methodology used in this study is based on Geographic Information Systems (GIS) and considers the supply and demand of urban services as well as the mobility patterns and behavioral traits of the population.
The application of the 2SFCA methodology in Naples reveals significant variations in accessibility levels. The findings indicate that substantial portions of the population, particularly in the urban periphery, experience poor accessibility to post offices, and that spatial accessibility to services varies remarkably depending on the setting of opening hours by Poste Italiane.
The study underscores the importance of tailored urban strategies in ensuring equitable access to essential services, thereby enhancing the quality of life
Structure analysis of human gut microbiota associated with single-celled gut protists using NGS sequencing of 16S and 18S rRNA genes
The gut microbiota is a complex microbial ecosystem with a major impact on health and disease. Some gut unicellular eukaryotes (particularly Blastocystis) have been linked to features of intestinal eubiosis. Meanwhile, little is known regarding associations between gut-pathogenic protozoa, such as Giardia, and gut microbiota signatures.
We therefore characterized and compared gut microbiota profiles of 60 Giardia-positive and 31 Giardia-negative Algerian individuals using amplicon-based next-generation sequencing of prokaryotic and eukaryotic ribosomal genes and stratifying for co-colonization with other unicellular eukaryotes, such as species of Archamoebae or Blastocystis.
Overall, we found that alpha and beta microbiota diversity did not differ significantly between Giardia-positive and Giardia-negative individuals, regardless of the presence or absence of Archamoebae, and Entamoeba (p > 0.05). However, significant differences were observed in both alpha and beta diversity between Giardia-positive, Blastocystis-negative and Giardia-positive, Blastocystis-positive individuals (observed richness, p = 0.0016; ANOSIM = 0.001), and similar differences were noticed between Blastocystis-negative and-positive carriers (p 0.05). Conclusively, Giardia-positive individuals may exhibit features of eubiosis, but whether this depends on the presence of Blastocystis should be confirmed by future studies. These findings combined might indicate that Blastocystis could be an active driver of gut microbiota diversity
Nuove e vecchie soluzioni in tema di “access to justice” e progressivo abbandono del simbolismo giudiziario
La relazione ha mira ad individuare il fil rouge che lega due trends apparentemente opposti: quello alla digitalizzazione della giustizia e quello all'approntamento di sistemi di giustizia itinerant
A Multi-Stage Framework Combining Experimental Testing, Numerical Calibration, and AI Surrogates for Composite Panel Characterization
Debris-cloud collision risk assessment with GSOC Collision Avoidance System
With the advancement of space technology, the rate of spacecraft launches has steadily increased, leading to growing congestion in Earth’s orbital environment. As a result, the likelihood of in-orbit break-ups has increased consistently, raising significant safety concerns about the potential collision risk posed by debris clouds to operational spacecraft.
Immediately following a break-up event, the process of tracking and cataloging every fragment begins. However, it takes time before the state of each piece of debris can be accurately estimated. This delay creates a "blackout" period during which satellite operators are unable to take mitigation actions to reduce collision risks. During this time, Conjunction Data Messages (CDMs) cannot be issued, making classical collision risk assessment methods for 1-vs-1 scenarios not suitable. Additionally, very small fragments often go untracked due to technological limitations of current sensors, potentially leading to a dangerous underestimation of the collision risk.
Within this framework, the Flight Dynamics (FD) team at the German Space Operations Center (GSOC) is developing a tool to evaluate the threat of fragmentation events to their assets, enhancing the capabilities of the existing and well-established Collision Avoidance System (CAS).
In detail, the proposed methodology maps the position evolution of a primary spacecraft into the initial spread velocity space at break-up time. This last is a conceptual space, where each point represents a ΔV caused by the break-up event. As the primary moves along its trajectory in physical space, its positions are mapped to the initial velocity a fragment would need at the moment of break-up to reach the primary at that specific location. This mapping is achieved by recursively solving a series of multi-revolution Lambert problems, with boundary conditions determined by the parent object’s position at break-up and the primary’s position at any given time. The collision risk is then calculated integrating all possible ΔVs that might result in a future collision over the initial velocity distribution of the cloud given by NASA’s Standard Break-up Model (SBM).
This results in a cumulative metric over time, which is then compared against a typical maneuvering threshold—a value at which operators would normally act to mitigate a conventional collision event.
The approach is tested on a benchmark case from the literature to demonstrate its effectiveness and applicability to real-world scenarios. Additionally, the sensitivity of the methodology to uncertainties in the break-up epoch is also examined. In particular, multiple break-up times are considered to identify the worst-case scenario in which the Probability of Collision (PoC) exceeds the maneuvering threshold at an earlier time, thereby allowing for a more effective and safer mitigation strategy
T.R.I.C.K. 2.0: Enhanced Vehicle Dynamics Analysis and Estimation Harnessing Advanced Vehicle Sensors
Automotive signal processing is dealt with in several contributions that propose various techniques to make the most out of the available data, typically for enhancing safety, comfort, or performance. Specifically, the accurate estimation of tire–road interaction forces is of high interest in the automotive world. A few years ago the T.R.I.C.K. tool was developed, featuring a vehicle model processing experimental data, collected through various vehicle sensors, to compute several relevant virtual telemetry channels, including interaction forces and slip indices. Following years of further development in collaboration with motorsport companies, this article presents T.R.I.C.K. 2.0, a thoroughly renewed version of the tool. Besides a number of important improvements of the original tool,
including, e.g., the effect of the limited slip differential, T.R.I.C.K. 2.0 features the ability to exploit advanced sensors typically used in motorsport, including laser sensors, potentiometers, and load cells installed on shock absorbers, anti-roll bars, and brake pressure sensors. Such information is harnessed in purposely-devised novel methodologies for estimating key quantities including roll angle, aerodynamic forces, and camber angle, all affecting tire–road interaction forces and friction ellipses. This is made possible by a completely modular structure of the tool able to employ the most accurate formulation depending on the sensors actually available