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Industry 5.0 has introduced new possibilities for defining key features of the factories of the future. This trend has transformed traditional industrial production by exploiting Digital Twin (DT) models as virtual representations of physical manufacturing assets. In the railway industry, Digital Twin models offer significant benefits by enabling anticipation of developments in rail systems and subsystems, providing insight into the future performance of physical assets, and allowing testing and prototyping solutions prior to implementation. This paper presents our approach for creating a Digital Twin model in the railway domain. We particularly emphasize the critical role of Big Data in supporting decision-making for railway companies and the importance of data in creating virtual representations of physical objects in railway systems. Our results show that the Digital Twin model of railway switch points, based on synthetic data, accurately represents the behavior of physical railway switches in terms of data points.

IntroductionImpaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.MethodsMonocentric, retrospective analysis. Male patients transplanted

The limitations of active noise control (ANC) in coping with low frequencies and of passive noise control (PNC) in coping with middle-high frequencies are objects of research that present the potentialities of hybrid noise control (HBC). It aims at combining both of the behaviours by broadening the range of absorbed frequencies. Among the several application fields, the AEC (architecture, engineering, and construction) market can take advantage for those applications in which the noise conditions are caused by sound sources that tune in a broad frequencies range. In this frame, the paper describes the numerical and experimental validation of the active behaviour of an under-development project of a hybrid noise control-based acoustic bricks. The latter intends to embed the potentialities of active vibrational noise control (AVC) and passive destructive interference (PDI) in a unique design of an easy-to-mount, 3D-printed, customisable smart acoustic blocks. Active vibration control, the object of this paper, is provided by a 5-mm thick aluminium circular plate with an attached piezoelectric patch. The vibration of the latter, depending on a specific control law, defines the vibration of the plate itself achieving an abatement of the reflection coefficient. Through mathematical modelling and tests in an impedance tube, the results show that the control logic can reach an average abatement of the reflection coefficient of 82% in the frequency range 144–1007 Hz.

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Despite the numerous advantages of using natural materials, such as fast-growing, living, and earthen materials, their widespread application in the construction industry remains limited. This research presents a perception survey, which investigates stakeholders' perceptions regarding the market, regulatory barriers, and educational barriers, exploring experiences, motivations, and attitudes toward the adoption of natural materials in construction projects. The results capture variations in current practices and identify patterns for future directions, analyzed in a comparative manner to assess two geographical regions: Europe and North America. The results show that contractor availability, a lack of professional knowledge (mostly in Europe), and cost-to-value perceptions (mostly in the USA) are key barriers to adopting natural materials. The lack of awareness among construction professionals regarding technical aspects highlights the need for targeted training, while the lack of regulatory distinction between living and earth-based materials underscores the need for harmonized policies. By elucidating stakeholders' perspectives and identifying key challenges, this research aims to inform policymaking, industry practices, and research initiatives aimed at promoting the use of a wider lexicon of construction materials. Ultimately, this study hopes to facilitate the development of strategies to overcome scalability challenges and accelerate the transition toward their implementation in mainstream projects. [ABSTRACT FROM AUTHOR]

Autophagy is a critical metabolic process that acts as a major self-digestion and recycling pathway contributing to maintain cellular homeostasis. An emerging field of research supports the therapeutic modulation of autophagy for treating human neurodegenerative disorders, in which toxic aggregates are accumulated in neurons. Our previous study identified Ezrin protein as an inhibitor of autophagy and lysosomal functions in the retina; thus, in turn, identifying it as a potential pharmacological target for increasing retinal cell clearance to treat inherited retinal dystrophies in which misfolded proteins have accumulated. This study aimed to verify the therapeutic inhibition of Ezrin to induce clearance of toxic aggregates in a mouse model for a dominant form of retinitis pigmentosa (i.e., RHOP23H/+). We found that daily inhibition of Ezrin significantly decreased the accumulation of misfolded RHOP23H aggregates. Remarkably, induction of autophagy, by a drug-mediated pulsatile inhibition of Ezrin, promoted the lysosomal clearance of disease-linked RHOP23H aggregates. This was accompanied with a reduction of endoplasmic reticulum (ER)-stress, robust decrease of photoreceptors' cell death, amelioration in both retinal morphology and function culminating in a better preservation of vision. Our study opens new perspectives for a pulsatile pharmacological induction of autophagy as a mutation-independent therapy paving the way toward a more effective therapeutic strategy to treat these devastating retinal disorders due to an accumulation of intracellular toxic aggregates.

Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo A) is one of the most severe lysosomal storage disorder (LSD) caused by the inherited deficiency of sulfamidase, a lysosomal sulfatase enzyme involved in the stepwise degradation of heparan sulfates (HS). MPS-IIIA patients show multisystemic problems, including a strong impairment of central nervous system (CNS), mild somatic involvement, and ocular manifestations that result in significant visual impairment. Despite the CNS and somatic pathology have been well characterized, studies on visual system and function remain partially explored. Here, we characterized the retina morphology and functionality in MPS-IIIA mouse model and analyzed how the SGSH deficiency affects the autophagic flux. MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function. The photoreceptor degeneration was associated with HS accumulation and a block of autophagy pathway. These events caused a reactive microgliosis, and a development of apoptotic processes in MPS-IIIA mouse retina. Overall, this study provides the first phenotypic spectrum of retinal disorders in MPS-IIIA and significantly contributes for diagnosis, counseling, and potential therapies development.

The technological advancements promote the rise of the fourth industrial revolution, where key terms are efficiency, innovation, and enterprises’ digitalization. Market globalization, product mass customization, and more complex products need to reflect on changing the actual design methods and developing business processes and methodologies that have to be data-driven, AI-assisted, smart, and service-oriented. Therefore, there is a great interest in experimenting with emerging technologies and evaluating how they impact the actual business processes. This paper reports a comparison among the major trends in the digitalization of a Factory of the Future, in conjunction with the two major strategic programs of Industry 4.0 and China 2025. We have focused on these two programs because we have had experience with them in the context of the FIRST H2020 project. European industrialists identify the radical change in the traditional manufacturing production process as the rise of Industry 4.0. Conversely, China mainland launched its strategic plan in China 2025 to promote smart manufacturing to digitalize traditional manufacturing processes. The main contribution of this review paper is to report about a study, conducted and part of the aforementioned FIRST project, which aimed to investigate major trends in applying for both programs in terms of technologies and their applications for the factory’s digitalization. In particular, our analysis consists of the comparison between Digital Factory, Virtual Factory, Smart Manufacturing, and Cloud Manufacturing. We analyzed their essential characteristics, the operational boundaries, the employed technologies, and the interoperability offered at each factory level for each paradigm. Based on this analysis, we report the building blocks in terms of essential technologies required to develop the next generation of a factory of the future, as well as some of the interoperability challenges at a different scale, for enabling inter-factories communications between heterogeneous entities.

Currently, various industrial processes are carried out in fluidized bed reactors. Knowing its internal dynamics is fundamental for the intensification of these processes. This work assesses the motion of fluidized calcium alginate spheres under the influence of an upward fluid flow within a 1.2 m high and 0.1 m inner diameter acrylic column. The liquid–solid fluidized bed was compared with a gas–liquid–solid fluidized bed operation mode in terms of mixing behavior. The radioactive particle tracking technique is a proper methodology to study the internal dynamics of these kinds of equipment. Data gathered were analyzed with Shannon entropy as a dynamic mixing measure. Mixing times were found to be between 1 and 2.5 seconds for both fluidization modes. The liquid–solid fluidized bed presents a rather smooth mixing time profile along the column. On the other hand, the gas–liquid–solid fluidized bed showed high sensitivity of entropy production with height, reaching a sharp tendency break at the second quartile of the column. The Glansdorff–Prigogine stability measure can accurately capture flow regime transitions of the gas–liquid–solid fluidized bed, allowing it to be used to construct reliable operative windows for fluidization equipment.

Summary: Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing β1-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties. : In this article, Farrukh and colleagues show that bifunctionalization of hydrogel substrates with polylysine and a 19-mer peptide containing the laminin motif IKVAV promotes neurogenesis from embryonic neuroblasts and adult neural stem cells. Neurogenesis and neurite outgrowth can be further optimized by adjusting gel stiffness in a cell-type-specific manner. Keywords: biomaterials, bioengineering, hydrogels, neural stem cells, cell differentiation, laminin, IKVAV, polylysine, β1-integrin, neurogenesis

Biomass with a large amount of moisture is well-suited to be processed by supercritical water gasification, SCWG. The precipitation of inorganics, together with char formation and re-polymerization, can cause reactor plugging and stop the process operations. When plugging occurs, sudden injections of relatively large mass quantities take place, influencing the mass flow dynamics significantly in the process. Reactor plugging is a phenomenon very well observed during SCWG of industrial feedstock, which hinders scale-up initiatives, and it is seldom studied with precision in the literature. The present study provides an accurate evaluation of continuous tubular reactor dynamics in the event of sudden injections of water. An interpretation of the results regarding water properties at supercritical conditions contributes to comprehending mass and heat transfer when plugging occurs. Experiments are then compared to SCWG of a biomass sample aiming to give key insights into heat transfer and fluid dynamics mechanisms that could help develop operational and control strategies to increase the reliability of SCWG. In addition, a simplified model is presented to assess the effect of material integrity on burst-event likelihood, which states that SCWG is safe to operate, at 250 bar and 610 °C, in tubular reactors made of 0.22 wall thickness-to-diameter ratio Inconel-625 with superficial microfractures smaller than 30 µm. We also suggest improvement opportunities for the safety of SCWG in continuous operation mode.

The skeletal dysplasia spondyloepiphyseal dysplasia tarda (SEDT) is caused by mutations in the TRAPPC2 gene, which encodes Sedlin, a component of the trafficking protein particle (TRAPP) complex that we have shown previously to be required for the export of type II collagen (Col2) from the endoplasmic reticulum. No vertebrate model for SEDT has been generated thus far. To address this gap, we generated a Sedlin knockout animal by mutating the orthologous TRAPPC2 gene (olSedl) of Oryzias latipes (medaka) fish. OlSedl deficiency leads to embryonic defects, short size, diminished skeletal ossification and altered Col2 production and secretion, resembling human defects observed in SEDT patients. Moreover, SEDT knock‐out animals display photoreceptor degeneration and gut morphogenesis defects, suggesting a key role for Sedlin in the development of these organs. Thus, by studying Sedlin function in vivo, we provide evidence for a mechanistic link between TRAPPC2‐mediated membrane trafficking, Col2 export, and developmental disorders. [ABSTRACT FROM AUTHOR]

Solid-liquid dissolution is a central step in many industrial applications such as pharmaceutical, process engineering, and pollution control. Accurate mathematical models are proposed to improve reactor design and process operations. Analytical methods are significantly beneficial in the case of iterative methods used within experimental investigations. In the present study, a detailed analytical solution for the general case of solid particles dissolving in multiphase chemical reaction systems is presented. In this model, the authors consider a formulation that considers the particles’ shape factor. The general case presented could be utilized within different problems of multiphase flows. These methods could be extended to different cases within the chemical engineering area. Examples are illustrated here in relation to limestone dissolution taking place within the Wet Flue Gas Desulfurization process, where calcium carbonate is dissolving in an acidic environment. The method is the most common used technology to abate SO2 released by fuel combustion. Limestone dissolution plays a major role in the process. Nevertheless, there is a need for improvements in the optimization of the WFGD process for scale-up purposes. The mathematical model has been tested by comparison with experimental data from several mild acidic dissolution assays of sedimentary and metamorphic limestone. We have found that R2 ⊂ 0.92 ± 0.06 from dozens of experiments. This fact verifies the model qualifications in capturing the main drivers of the system.