Circular RNAs (circRNAs) are single-stranded RNA molecules often circularized by backsplicing. Growing evidence implicates circRNAs in the underlying mechanisms of various diseases, such as Alzheimer's and Parkinson's disease (PD) - the first and second most prevalent neurodegenerative disorders. Several circRNAs are associated with brain damage, including circSNCA, circHIPK2, circHIPK3, and circSLC8A1. Gain-of-function and loss-of-function studies on circRNAs have shed light on their roles in the pathobiology of various diseases. Gain-of-function approaches typically employ viral or non-viral vectors that hyperexpress RNA sequences capable of circularizing to form the specific circRNA under investigation. In contrast, loss-of-function studies utilize CRISPR/Cas systems, antisense oligonucleotides (ASOs), or RNAi techniques to knockdown the target circRNA. Given that aberrantly expressed circRNAs have been associated with brain pathologies, a critical question arises: could circRNAs serve as viable targets for neuroprotective treatments? Translating any oligonucleotide-based therapy, including those targeting circRNAs, involves developing adequate brain delivery systems, minimizing off-target effects, and addressing the high costs of treatment. Nonetheless, RNAi-based FDA-approved drugs have entered the market, and circRNAs have attracted significant attention and investment from major pharmaceutical companies. Spanning from bench to bedside, circRNAs present a vast opportunity in biotechnology for oligonucleotide-based therapies designed to slow or even halt the progression of neurodegenerative diseases.

To maintain proteostasis, cells must integrate information and activities that supervise protein synthesis, protein folding, conformational stability, and also protein degradation. Extrinsic and intrinsic conditions can both impact on normal proteostasis, causing the appearance of proteotoxic stress. Initially, proteotoxic stress elicits adaptive responses aimed to restore proteostasis, allowing cells to survival the stress condition. However, if the proteostasis restoration fails, a permanent and sustained proteotoxic stress can be deleterious and cell death ensues. Many cancer cells convive with high levels of proteotoxic stress and this condition could be exploited in a therapeutic perspective. Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.

Several plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in nature and have been utilized by man for pharmaceutical and agrochemical purposes. There are more than 3000 EOs reported in the literature with approximately 300 having commercial use, including the oils from Eucalyptus species. Such oils are rich in monoterpenes and have found applications as pharmaceuticals, agrochemicals, food flavorants and in the perfume industry. Such applications are related to their diverse biological and organoleptic properties. In view of their importance, we review in this article up to date information concerning chemical composition and biological activities of essential oils from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus¸ we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricide, insecticide and herbicide activities, hoping that such information will contribute in the advances of the research in this field. It is also intended that the information herein described can be useful in the rationalization of the use of Eucalyptus EOs as components for new pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

The details of abiogenesis to date remain a matter of debate and constitute a key mystery in science and philosophy. The prevailing scientific hypothesis implies an evolutionary process of increasing complexity on earth starting from (self-) replicating polymers. Defining the cut-off point where life begins is another moot point beyond the scope of this article. We will instead walk through the known evolutionary steps that lead from these first exceptional polymers to the vast network of living biomatter that spans our world today, focusing in particular on perception, from simple biological feedback mechanisms to the complexity that allows for abstract thought. We then will project from the well-known to the unknown to gain a glimpse on what the universe aims to accomplish with living matter, just to find that if the universe had ever planned to be comprehended, evolution still has a long way to go.

The biomass fraction of processed municipal and industrial wastes added to soil can maintain, and in some case improve, the soil’s organic fertility. One of the main constraints in the agricultural use of the sewage sludge is its content of heavy metals. In the long term, soil administration of sewage sludge in agriculture could result in a risk of environmental impact. The aim of this research was to evaluate the effects of medium-term fertilization with sewage sludge diversely processed on the soil’s organic carbon content and humification – mineralization soil’s processes and on the physical and mechanical properties of soil. Furthermore, the heavy metals accumulation in soil, in their total and available form, has been investigated. After eight years of administration to soil, the use of sewage sludge as an agricultural soil amendment has contributed to maintaining the soil’s organic fertility. An increase in concentrations of total Ni and Zn was detected in soil. For bioavailable form (DTPA-extractable) this trend was evidenced for all heavy metals analysed. However, the concentrations of total and available heavy metals in the soil did not exceed the legal threshold established by Italian law for unpolluted soils.

In emergency situations, every second counts for an ambulance navigating through traffic. Efficient use of traffic light systems can play a crucial role in minimizing response time. This paper introduces a novel automated Real-Time Ambulance in an Emergency Detector (RTAIAED). The proposed system uses special Lookout Stations (LS) suitably positioned at a certain distance from each involved traffic light (TL), to obtain timely and safe transitions to green lights as the Ambulance in an Emergency (AIAE) approaches. The RTAIAED is particularly pertinent on one-way roads, addressing the challenge of regulating the sequence of traffic-lights-signals so as to minimize the time needed to safely grant the green signal to the AIAE. The proposed solution leverages a part-based model made of elementary detectors for video analysis, specifically realized with a customized YOLOv8 model, and for audio analysis, thanks to an additional neural network based on Mel Frequency Cepstral Coefficients (MFCCs). This way, the RTAIAED ensures the accurate and robust identification of an AIAE heading towards a traffic light in time to ensure a green light thanks to the strategic positioning of the LS detectors. Extensive experiments demonstrate the robustness of the approach and its reliable application in real-world scenarios thanks to its predictions in real-time, showcasing the ability to detect AIAEs even in challenging conditions such as noisy environments, nighttime, or adverse weather conditions, provided a suitable-quality camera is appropriately positioned. The proposed system can also find application in traffic flow management.

This paper presents the validation of the End Point Rate (EPR) tool for QGIS (EPR4Q), a tool built-in QGIS Graphical Modeler to calculate the shoreline change by End Point Rate method. The EPR4Q tries to fill the gap of user-friendly and free open-source tool for shoreline analysis in Geographic Information System environment, since the most used software - Digital Shoreline Analysis System (DSAS) - although is a free extension, is suited for commercial software. Besides, the best free open-source option to calculate EPR called Analyzing Moving Boundaries Using R (AMBUR), since it is a robust and powerful tool, the complexity and heavy processes can restrict the accessibility and simple usage. The validation methodology consists of applying the EPR4Q, DSAS, and AMBUR on different examples of shorelines found in nature, extracted from the U.S. Geological Survey Open-File. The obtained results of each tool were compared with Pearson correlation coefficient. The validation results indicate that the EPR4Q tool created acquired high correlation values with DSAS and AMBUR, reaching a coefficient of 0.98 to 1.00 on linear, extensive, and non-extensive shorelines, guarantying that the EPR4Q tool is ready to be freely used by the academic, scientific, engineering, and coastal managers communities worldwide.

Solid waste management is challenging in many countries, especially developing economies. The impacts of the pandemic continue to be felt and have indicated secondary impacts on waste management. This work draws on data on household solid waste (HSW), healthcare waste (HCW), and recyclables collected in the Rio de Janeiro municipality, analyzed from January 2018 to December 2022. As expected, the collection of HCW in Rio de Janeiro municipality experienced a noticeable increase in 2020 and 2021, with an average of 46.9 tons and 54.3 tons collected, respectively. Notably, 2021 saw a significant 30% increase compared to 2019 (p-value<0.001). No significant difference was observed in recyclables collected from 2018 to 2021. The average recyclable amount was 3,638 and 3,747 tons per month in 2020 and 2021. In contrast, the monthly amount was equal to 4,819.5 tons in 2022, representing an increase higher than 32% compared to previous years (p-value<0.05). Our findings can be used to adapt and improve waste systems to cope with similar emergency scenarios in the future, serving as a template for municipalities with similar challenges.

This study compares the action of different handpieces (turbine, high-speed electric handpiece and piezoelectric device) on surface roughness of enamel and dentin when using diamond-coated working tips and burs of the same grit size. Experiment was conducted on 15 extracted first molars from patients aged 45 to 60 years. The occlusal portion was removed using a diamond-coated water wheel and then refined with a 120-130 μm grit bur in order to obtain a flat surface with an adequate exposition of the dentin core. Each surface was divided into three portions and every portion was finished with one of the three tested instruments. Rotary burs and piezoelectric tips had the same grit size (60 μm) and load on handpiece during preparation never exceeded 150 g. Surface roughness parameters (Ra, Rsk, Rku) were recorded with an optical profilometer and SEM analysis of treated surfaces and working tips was conducted. Ra and Rsk differed significantly between enamel and dentin only after using turbine (p=0.004 and p=0.007, respectively). No significant differences were observed in Ra, Rsk, and Rku between enamel and dentin when using high-speed electric handpiece or piezoelectric device. Turbine produced higher Ra and Rsk values on dentin than the other devices, while no significant differences were found between piezoelectric handpiece and high-speed electric contra-angle on both substrates. Summarizing, the findings of the present study demonstrated that turbine generated rougher surfaces on dentin compared to the other handpieces. Moreover, the turbine produced more asymmetrical surface profiles on both enamel and dentin. However, it should be considered that these differences in roughness (Ra) were within the range of 0.25-0.30 μm: it is still unclear if these variations, although statistically significant, will influence final clinical outcomes.

Exercises for lower trapezius (LT) often use overhead positions, causing compressive forces to the subacromial space. Scapular retraction would be an alternative to activate LT muscle. Electromyography of infraspinatus (IS), upper (UT) and LT was recorded during scapular retraction under progressive adduction loads of 42 participants, divided in 2 groups: with (SP, n=26) and without shoulder pain (nSP, n=16). The adduction loads of 20, 30, 40 and 50% of the maximal voluntary contraction were applied using a load cell. Normalized electromyography and the ratio between UT and LT (UT:LT) were used for statistical analysis. No differences were observed between groups, but a condition effect occurred for all muscles: UT showed higher values at 50% vs. 20% (p=0.004); LT showed higher values on 40% and 50% (p=0.001; 0.006). Higher values for IS were noted at 40% (vs 20%; p=0.04), and at 50% (vs. 20%; p=0.001, vs. 30%, p=0.001; vs. 40%; p=0.001). UT:LT showed lower values at 50% (vs. 20%; p=0.001, and vs. 30%; p=0.016). Scapular retraction with adduction loads at 40-50% is an alternative to overhead exercises aiming to activate the LT and the IS muscles. The exercise ensures higher levels of LT and IS excitation, without increasing UT excitation.

This study examines the behavior of stearic acid (SA) and 12-hydroxystearic acid (12-HSA) aqueous mixtures as a function of temperature and 12-HSA/SA molar ratio (R). Whatever R, the system exhibits a morphological transition at a given threshold temperature, from multilamellar self-assemblies at low temperature towards small micelles at high temperature, as shown by a combination of transmittance measurements, Wide Angle X-ray diffraction (WAXS), small angle neutron scattering (SANS) and differential scanning calorimetry (DSC) experiments. Such transition originates from the melting of the crystallized fatty acids within the lamellar phase. The precise determination of the threshold temperature, which ranges between 20°C and 50°C depending on R, allows for the construction of the whole phase diagram of the system as a function of R. At high temperature the micelles that are formed are oblate for pure SA solutions (R = 0) and prolate for pure 12-HSA solution (R = 1). In the case of mixtures, there is a progressive continuous transition from oblate to prolate shape when increasing R, with micelles that are almost purely spherical for R = 0.33.

Iron ore processing involves critical steps that affect the quality of the final product. Determining the diameter of the pellets is the necessary initial step for volume measurement and, ultimately, for porosity and bulk density measurement, crucial characteristics for optimizing the burning process in the blast furnace. Traditional measurement methods using mercury present issues related to operator safety and environmental preservation, while the practices described in ISO 4698 standard require lengthy preparation and execution time. In light of environmental needs, operator safety, and the time consumed in tests, implementing a new method based on digital image processing and convolutional neural networks for measuring the diameter of burnt iron ore pellets is proposed. The methodology involves capturing images of the pellets using a high-resolution camera and utilizing digital image processing and neural networks capable of performing pixel-by-pixel object segmentation in the images, providing precise information about the pellets to calculate their volume automatically. The results were compared with those obtained using traditional methods, evaluating their conformity with the ISO 4698 standard. In conclusion, this study offers a new approach to measuring the volume of burnt iron ore pellets, providing accurate and reliable results in compliance with safety and environmental preservation standards.

This study aimed to characterize the risk of falling in low, moderate and high risk participants from two different geographical locations using a portable force-plate. A sample of 390 older adults from South and North America were matched for age, sex, height and weight. All participants performed a standardized balance assessment using a force plate. Participants were classified in low, moderate and high risk of falling. No differences were observed between South and North American men, nor comparing North American men and women. South American women showed the significantly shorter center of pressure path length compared to other groups. The majority of the sample was categorized as having low risk of falling (male: 65.69 % and female: 61.87 %), with no differences between men and women. Also, no differences were found between North vs. South Americans, nor for falls risk levels when male and female groups were compared separately. In conclusion, South American women had better balance compatible with the status of the 50-59 years’ normative age-range. The prevalence of low falls risk was ~ 61-65 % and the prevalence of moderate to high risk was ~ 16-19 %. The frequency of fall risk did not differ significantly between North and South Americans, nor between males and females.

Small and micro hydropower represents an attractive solution for electricity generation, with low cost and low environmental impact. The pump-as-turbine (PAT) approach has promise in this application owing to its low purchase and maintenance costs. In this paper, a new method to predict the inverse characteristic of industrial centrifugal pumps is presented. This method is based on results of simulations performed with commercial three-dimensional CFD software. Model results have been first validated in pumping mode using data supplied by pump manufacturers. Then, results have been compared to experimental data for a pump running in reverse condition. Experimentation has been performed on a dedicated test bench installed in the Department of Civil Construction and Environmental Engineering of the University of Naples Federico II. Three different pumps, with different specific speeds, have been analyzed. Using the model results, the inverse characteristic and the best efficiency point have been evaluated. Finally, results of this methodology have been compared to prediction methods available in the literature.

In the last two decades, the continuous ever growing demand for energy has determined a significant development in the production of photovoltaic (PV) modules. Anyway, a critical and very important issue in the module design process is the adoption of suitable encapsulant materials and technologies for cell embedding. Therefore, adopted encapsulants have a significant impact on modules efficiency, stability and reliability, and to ensure the unchanged performance of PV modules in time, the encapsulant materials must be selected properly. The selection of encapsulant materials must maintain a good balance between the encapsulant performance in time and costs, related to materials production and technologies for cells embedding. However, the encapsulants must ensure excellent isolation of active photovoltaic elements by the environment, preserving accurately the PV cells against humidity, oxygen and accidental causes that may compromise the PV modules function. This review provides an overview of different encapsulant materials, their main advantages and disadvantages in adoption for PV production, and also in relation to used encapsulant technologies for cell embedding, additives and the interaction of these materials with other PV components.

Magneto-electrochemistry (MEC) is a unique paradigm in science, where electrochemical experiments are carried out as a function of an applied magnetic field, creating a new horizon of potential scientific and technological applications. Over the time, detailed understanding of this research domain was developed to identify and rationalize the possible effects exerted by a magnetic field on the various microscopic processes occurring in an electrochemical system, such as: electrolyte properties governed by charge-transfer process (electric conductivity, viscosity, and diffusivity), mass transfer, electrochemical kinetics and on the structure/quality of products formed either at the working electrode or in the electrochemical cell. Particularly, magnetic field controlled chiral architecture obtained from deposited metal, alloys and catalyst and their excellent enantio-recognition in experimental frame is highly appealing. Interestingly, Hall effect was also demonstrated in electrolytic medium via an impressive experimental technique which is being employed for further theoretical understanding in the field of magneto-electrochemical science. Later, a highly reproducible local temperature variation was observed in electrochemical electrolytes exposed to perpendicular magnetic and electric fields. However, until recent studies, none of the above mentioned reports considered the possibility of a spin-dependent related charge-transfer process. Recent experimental and theoretical studies reveal that electron’s transmission through chiral molecules is spin-selective and this effect has been referred to as chiral-induced spin-selectivity (CISS) effect. The CISS effect pave the way for the building up of a system characterized by a net magnetic moment exploiting the spin-filtering ability of chiral molecules. This interplay between chirality and magnetism may shed light on fundamental scientific aspects underlying the enantio-recognition and highly efficient electron-transfer that occurs in biological process.

(1) Background: Hand hygiene practice by using alcohol-based hand sanitizers was generalized in all sectors of activity, due the COVID-19 pandemic. The aim of this study was to organize and analyze the scientific data regarding occupational exposure to hand sanitizers, with a particular focus on their use and health effects on workplace settings. (2) Methods: A rapid literature review was carried out searching on the main scientific database, namely: Web of Science Core Collection, Medline, Scielo and Current Content Connect. (3) Results: All studies analyzed included samples from healthcare professionals and eczema as well as irritant contact dermatitis were the most reported skin lesions. (4) Conclusions: The adequate implementation of hygiene and disinfection programs in workplaces is essential to guarantee the workers safety and health. Further research is needed on the effectiveness of contingency plans in different sectors of activity, particularly, in industry.

The paper analyses how between 1956 and 2009 the agrarian metabolism of the Barcelona Metropolitan Region (BMR) has become less functional, losing circularity in biomass flows and in relationship to its landscape. We do so by adopting a Multi-EROI and flow-fund (MuSIASEM) analyses and its nexus with landscape functional structure. The study of agricultural flows of Final Produce, Biomass Reused and External Inputs is integrated with that of land use, livestock, power capacity and population changes between 1956 (at the beginning of the Green Revolution) and 2009 (fully industrialized agriculture). A multi-scale analysis is conducted at the landscape scale (seven districts within the Barcelona metropolitan region) as well as for the functions deployed, within an agroecosystem, by the mutual interactions between its funds (land-uses, livestock and farming population). A complex nexus between land, livestock, dietary patterns and energy needs is shown; we conclude that from the perspective of the circular bioeconomy the agrarian sector has gone worse hand in hand with the landscape functional structure. Therefore, a novel perspective in landscape agroecology is opened

SOX proteins are transcription factors which play a role in regulating the development of pro-genitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A to H, and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group together with SOX11 and SOX12. SOX4 variants were recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delay and learning difficulties to intellectual disability with congenital anomalies. Nineteen pathogenic variants were reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants, leading to whole gene deletion or duplication, are rare and not clearly associated with a neurodevelopmental disorder. Many open questions remain, regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.

Semi-supervised consensus clustering is a promising strategy to compensate for the subjectivity of clustering and its sensitivity to design factors, with various techniques being recently proposed to integrate domain knowledge and multiple clustering partitions. In this article we present a new approach that makes double use of domain knowledge, namely to build the initial partitions as well as to combine them. In particular, we show how to model and integrate must-link and cannot-link constraints into the objective function of a generic consensus clustering (??) framework that maximizes the similarity between the consensus partition and the input partitions, which have, in turn, been enriched with the same constraints. In addition, borrowing from the theory of functional dependencies, the integrated framework exploits the notions of deductive closure and minimal cover to take full advantage of the logical implication between constraints. Using standard UCI benchmarks, we found that the resulting algorithm, termed ??? (double-Constrained Consensus Clustering), was more effective than plain ?? at combining base constrained partitions. We then argue that ??? is especially well-suited to profiling counterfeit e-commerce websites, because constraints can be acquired by leveraging specific domain features, and demonstrate its potential for detecting affiliate marketing programs. Taken together, our experiments suggest that ??? makes the process of clustering more robust and able to withstand changes in clustering algorithms, datasets, and features, with a remarkable improvement of average performance.

The copper mining industry is increasingly using artificial intelligence methods to improve cop-per production processes. Recent studies reveal the use of algorithms such as Artificial Neural Network, Support Vector Machine, and Random Forest, among others, to develop models for predicting product quality. Other studies compare the predictive models developed with these machine learning algorithms in the mining industry, as a whole. However, not many copper mining studies published compare the results of machine learning techniques for copper recovery prediction. This study makes a detailed comparison between three models for predicting copper recovery by leaching, using four datasets resulting from mining operations in northern Chile. The algorithms used for developing the models were Random Forest, Support Vector Machine, and Artificial Neural Network. To validate these models, four indicators or values of merit were used: accuracy (acc), precision (p), recall (r), and Matthew’s correlation coefficient (mcc). This paper describes dataset preparation and the refinement of the threshold values used for the predictive variable most influential on the class (the copper recovery). Results show both a precision over 98.50% and also the model with the best behavior between the predicted and the real. Finally, the models obtained show the following mean values: acc=94.32, p=88.47, r=99.59, and mcc=2.31. These values are highly competitive as compared with those obtained in similar studies using other approaches in the context.

Specialized, reductionist, and linear approaches are applied in clinical research; they are based on linear logic and used towards therapeutic molecule-based targets. However, those approaches do not consider a systemic vision that describes the remote cause of the pathogenic activation. We propose new theoretical and practical methods for the next drug generation development. Self-organization, network structure, hierarchical organization, non-linearity, feedback circuits, reactions to information, and the view of drugs as information clarify the existing pharmacological methods. We suggest a perspective and hierarchical vision of the human organism based on six levels (mechanic and structural; metabolic; bodily dynamic; emotional, cognitive, spiritual). The therapy should restore the self-organization of every level using the “intelligent” modulation of the network responses. Multi-targeted drugs should act on the remote cause of the pathogenic cascade and be administered based on personal variability and networks. This approach may help the development of individualized, precise, and integrated medicine.

Plant trichomes are specialized unicellular structures that originate and project from above ground epidermal tissues on the surfaces of leaves, petals, stems, petioles, peduncles, and seed coats depending on species. Trichomes (also called ‘hairs’) play well-recognized roles in defense against insect herbivores, both as a physical barrier that obstructs herbivore movement and by mediating chemical defenses. By virtue of their physical properties (size, density), trichome hairs can directly operate to protect buds of plants from insect damage, reduce leaf temperature, increase light reflectance, prevent water loss, and decrease leaf abrasion. Great variety of trichomes and their accessibility makes them a useful model for studying the molecular processes of cell fate determination, cell cycle control and cellular morphogenesis. In leaves, the developmental control of the trichomatous complement has highlighted a regulatory network based on four fundamental elements: (i) genes that activate and/or modify the normal cell cycle of epidermal cells (i.e. endoreduplication cycles); (ii) transcription factors that create activator/repressor complexes with a central role in determining cell fate, initiation and differentiation of an epidermal cell in trichome; (iii) evidences that point out the interplay of the aforesaid complexes with various phytohormones; (iv) epigenetic mechanisms involved in trichome development. Here, we describe trichome development in leaves, commonly subjected to environmental injury, and where most genetic regulators have been characterized.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

The impact of controlled breathing on cognitive and affective processing has been recognized since ancient times, giving rise to multiple practices aimed at achieving different psychophysical states, mostly related to mental clarity and focus, stress reduction and relaxation. Previous scientific research explored the effects of unilateral nostril breathing (UNB) over brain activity, emotional and cognitive functions. Most evidence concluded for a contralateral effect, but many other controversial results make it difficult to come to an unambiguous interpretation. In the present study, we invited a pilot sample of 20 participants to take part in an 8-days breathing training, assigned either to the right nostril (URNB) or the left nostril breathing condition (ULNB). Then, each day, we assessed participants’ well-being indices with mood and mind-wandering scales. Results revealed that, after the daily practice, both groups reported improved well-being perception. However, the effect was specifically related to the nostril involved. URNB produced more benefits in terms of stress reduction and relaxation, while ULNB significantly reduced mind-wandering occurrences, increasingly over time. Our results are only partially in agreement with previous evidence, indicating the need for a more complex interpretive model that considers multiple brain networks and integrates central and peripheral nervous systems.

Nickel-based ethylene polymerization catalysts have unique features, being able to produce macromolecules with a variable content of branches, resulting in polymers ranging from semicrystalline plastics to elastomers to hyperbranched amorphous waxes and oils. In addition to Brookhart's α-diimine catalysts, iminopyridine Ni(II) complexes are among the most investigated systems. We report that Ni(II) complexes bearing aryliminopyridine ligands with bulky substituents both at the imino moiety and in the 6-position of pyridine afford either hyperbranched low molecular weight polyethylene oils or prevailingly linear crystalline polyethylenes or both depending on the ligand structure and the reaction conditions. The formation of multiple active species in situ is suggested by analysis of the post-polymerization catalyst residues, showing the partial reduction of the imino function. Some related arylaminopyridine Ni(II) complexes were also synthesized and tested, showing a peculiar behavior, i.e. the number of branches of the produced polyethylenes increases while ethylene pressure increases.

This study presents an in-depth analysis and evaluation of self-healing networks as an innovative solution to combat the escalating threat of ransomware attacks. Recognizing the limitations of traditional network security methods in the face of advanced cyber threats, the research focuses on the development and implementation of self-healing networks, characterized by their dynamic, intelligent response systems. Utilizing a combination of artificial intelligence and machine learning algorithms, these networks demonstrate remarkable adaptability and resilience. Through rigorous simulations, the study examines the efficacy of self-healing networks in detecting, isolating, and recovering from ransomware attacks, with an emphasis on their ability to learn and evolve from each incident. The research highlights the strengths and limitations of these networks and discusses their potential applications in various sectors. The findings suggest that self-healing networks, with their proactive and adaptive defense mechanisms, represent a significant advancement in cybersecurity strategies, offering a robust solution against a range of cyber threats. Future work is recommended to further enhance the capabilities of self-healing networks, particularly in the areas of speed, detection accuracy, and quantum-resistant security measures.

This research looks into the evolving dynamics of ransomware, shifting from conventional encryption-based attacks to sophisticated data exfiltration strategies. Employing the Bidirectional Encoder Representations from Transformers (BERT) model, the study analyzes network traffic patterns to detect ransomware activities, offering new insights into their covert operations. The findings emphasize the need for advanced AI tools in cybersecurity, highlighting the significance of adapting and innovating defense strategies to counter the changing landscape of ransomware threats. The study contributes to a deeper understanding of ransomware evolution and underscores the importance of integrating AI in cybersecurity practices.

Background: The financial austerity policy imposed to Portugal by Troika - the European Commission, European Central Bank and International Monetary Fund in 2011, led to a tremendously social crisis. Under these dominant trends in Europe, which were felt especially in certain countries, such as Portugal, we feel ourselves forced into an analysis and reflection on the impact of this conjuncture in social workers, especially analyzing the role played by social workers and its critical consciousness relative to this neoliberal model and imposed austerity policies. Methods: This article results from an analysis of empirical data collected after the entry of Troika in Portugal, during 2013. Were conducted 26 in-depth interviews to front line social workers, with the purpose of obtaining a narrative of their daily work practice and with the concern of encouraging reflection on them. Results: Analysis shows the predominance of a maintenance role at the expense of more emancipatory approaches and thus, this results point to the relationship of this maintenance role with the sociological paradigm of social regulation and shows also, how social work is still attached to a conservative agenda. Secondly, one finds a weak critical reflection among social workers, being very afraid to speak out against the system, taking on a submissive attitude and subservient to the policies of social cuts imposed. The analysis then raises the challenge for social workers to develop a critical reflexivity Conclusion: The results highlight several important observations in terms of social woker role and that a critical activity is urgently required to social workers.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodents’ populations during active and quiescent periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses had shown that all rodent species occurred through the whole territory of the municipality with different hotspots for the risk of occurrence of the different species. Important fluctuation in the rodent populations was observed with a reduction in the wild rodent fauna following the end of a plague epidemic period, mostly represented by Necromys lasiurus and increase of the commensally species Rattus rattus. A higher abundance of rats might lead to an increased exposure of humans populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis contributed to further highlight the role of the wild rodent species as the amplifier hosts and of the commensally rats (Rattus rattus) as the preserver hosts on the quiescent period on that transmission infection area.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

In this study, I will present some documentary evidence that Carlos Drummond de Andrade’s poem “A Máquina do Mundo” [The Machine of the World] (1949) was based on prior reflections contained in a forgotten newspaper article entitled “Poesia e Pesadelo” [Poetry and Nightmare] (1949). In that article, Drummond critically analyzed some of the theses of Stephen Spender's essay “What Is Modern in Modern Poetry” (1948), which had just been published in The Tiger's Eye magazine. As soon as he read Spender's text, Drummond wrote “Poetry and Nightmare” and began to elaborate a narrative poem whose protagonist would be a machine. All the documentary evidence indicates that Drummond took Spender's lessons as touchstones for the elaboration of the narrative and allegorical structure of “The Machine of the World.” According to the interpretation I am proposing here, Drummond, in writing the machine poem, put into practice at least six lessons drawn from Spender’s essay, namely: 1) the modern poet must represent the tension between the external machinelike landscape and the landscape of the inner world of the creative imagination; 2) he must also represent the machinelike, ugly, and urban world around him in a beautiful and poetic way; 3) he must avoid the misconceptions of excessive utopian visionarism, as well as creeping realism; 4) he must reject the imperative of political engagement, whose principle of action states that poetry has a transformative mission in society; 5) he must free himself from the obsession with free verse as the only form of modern poetry and start using the traditional fixed forms; 6) he must understand machines as poetic symbols of human passions, and not just as exotic objects foreign to human reality. My conclusion is that, after reading Spender’s essay, Drummond changed his aesthetic and philosophical understanding of what defines the essence of modern poetry, both in terms of form and content.

Unmanned Aerial Vehicles (UAVs) in particular multirotors are becoming the {\it de facto} tool for aerial sensing and remote inspection. In large industrial facilities, a UAV can transmit an online video stream to inspect difficult to access structures, such chimneys, deposits and towers. However, the communication range is limited, constraining the UAV operation range. This limitation can be overcome with relaying UAVs placed between the source UAV and the control station, creating a line of communication links. In this work we assume the use of a digital data packet network technology, namely WiFi, and tackle the problem of defining the exact placement for the relaying UAVs that creates an end-to-end channel with maximal delivery of data packets. We consider asymmetric communication links and we show an increase as large as $15$\% in end-to-end packet delivery ratio when compared to an equidistant placement. We also discuss the deployment of such a network and propose a fully distributed method that converges to the global optimal relay positions taking, on average, 1.4 the time taken by a centralized method.

Traditional high pressure mechanical compressors account for over half of the car station’s cost, have insufficient reliability and are not feasible for a large-scale fuel cell market. An alternative technology, employing a two-stage, hybrid system based on electrochemical and metal hydride compression technologies, represents an excellent alternative to conventional compressors. The high-pressure stage, operating at 100-875 bar, is based on a metal hydride thermal system. A techno-economic analysis of the metal hydride system is presented and discussed. A model of the metal hydride system was developed, integrating a lumped parameter mass and energy balance model with an economic model. A novel metal hydride heat exchanger configuration is also presented, based on mini-channel heat transfer systems, allowing for effective high-pressure compression. Several metal hydrides were analyzed and screened, demonstrating that one selected material, namely (Ti_0.97Zr_0.03)_1.1Cr_1.6Mn_0.4, is likely the best candidate material to be employed for high-pressure compressors under the specific conditions. System efficiency and costs were assessed based on the properties of currently available materials at industrial levels. Results show that the system can reach pressures on the order of 875 bar with thermal power provided at approximately 150 °C. The system cost is comparable with the current mechanical compressors and can be reduced in several ways as discussed in the paper.

Background: To assess effectiveness, safety of computed tomography (CT)-guided cryoablation for treating adrenal metastases (AMs). Materials and Methods: This study involved 12 patients treated with 13 CT-guided cryoablation procedures for AMs between 2016 and 2020. Patients’ ineligible for surgery, with tumors ≤5 cm, and no significant health risks were included. The procedures, conducted by expert radiologists, included initial non-contrast CT scans to determine lesion morphology, followed by cryoablation with monitoring for complications. Post-treatment, patients underwent regular physical and laboratory checks, including hormonal analysis, and CT scans at specified intervals to assess the treatment's effectiveness and detect disease recurrence or progression. Results: In this study, 12 patients with AMs successfully underwent cryoablation, achieving a primary technical success rate of 91.7% and a secondary rate of 100% after a repeat procedure for one patient. All cryoablation sessions were completed without major complications, with ice ball formations extending 1 cm beyond tumor margins to ensure safety. Over an 8–24-month follow-up (average 16.3 months), six patients required further systemic therapy, with three developing extra-adrenal tumors. Local progression was noted in two patients (16.7%), one of whom underwent a repeat cryoablation. Systemic progression was observed in five patients, involving renal and NSCLC cancer recurrences and bone metastasis. The study reported five deaths due to tumor progression and heart failure, with an average overall survival duration of 32.4 ± 7.6 months.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

This study examined the efficiency of a combined diagnostic approach in which bioamplification of Arizona 861 S1 citron was integrated with RT‒PCR to detect Citrus tristeza virus (CTV) and Hop Stunt Viroid (HSVd) in Citrus plants. The capacity of the combined method to diagnose mixed infections of CTV and HSVd, along with early single infections of both pathogens, was assessed by evaluating the incubation periods and differential detection capabilities between the combined and direct methods. The bioamplification method exhibited high sensitivity (100%) and specificity (100%) for CTV, enabling early detection even in patients with low-titer infections compared to direct RT‒PCR. However, for HSVd, the combined method achieved 50% sensitivity in early infections, highlighting the need for additional replicates to enhance diagnostic reliability. The relative concentrations of pathogens in mixed and simple infections were evaluated; the analysis revealed no significant differences, suggesting minimal interference between CTV and HSVd. This approach allows early detection of CTV but requires further refinement for HSVd diagnosis. These findings underscore the complementary roles of the cost-effectiveness of direct RT‒PCR and the sensitivity of the combined method in implementing effective disease control strategies in citrus crops.

The specialisation and intensification in agriculture have increased the productivity but have also led to the spread of monocultural systems, simplifying production and reducing genetic diversity. The purpose of this study was to propose crop diversification as a tool to increase biodiversity and achieve sustainable and resilient intensive agriculture, particularly in areas with water scarcity. In this paper, a combined Life Cycle Assessment (LCA) and Life Cycle Costing (LCC) was applied to evaluate the environmental and economic sustainability of a differentiated system of cultivation (pomegranate, almond and olive), according to modern intensive and superintensive cropping systems. Based upon the results obtained, it is deduced that pomegranate cultivation generated the highest environmental load, followed by almond and olive. From the financial analysis, it emerged that almond is the most profitable, followed by pomegranate and olive.

This study analyzes the convergence between artificial intelligence (AI) and management accounting in hospital contexts. Management accounting plays a central role in the effectiveness of planning, control and decision-making in healthcare institutions such as hospitals. The application of AI in this scenario offers powerful tools to improve accounting processes, optimize operational efficiency and maximize the use of available resources, resulting in an improvement in the quality of care provided to patients. Through in-depth analysis, the article explores how AI is bringing about a revolution in hospital management accounting, presenting case studies illustrating its successful implementation, outlining the tangible benefits.

During summer 2016 in the District of Palermo, Italy, the rapid succession of four cases of invasive meningococcal disease among young adults, with one death, have had an extraordinary emphasis by Local and National mass media. The resultant “epidemic of panic” among general population overloaded vaccination Units of the Palermo District during following months. Strategies implemented by Sicilian and Local Public Health Authorities to counteract “meningitis fear” were: a) extension of active and free of charge anti-meningococcal tetravalent vaccination from age class 12–18 to 12–30 years old; b) implementation of vaccination units usual opening hours and rooms tailored for vaccine administration; c) development of informative institutional tools and timely communications throughout local mass media to reassure general population. In 2016, was observed an increase of anti-meningococcal coverage in Palermo District (+18% for 16th y.o. and + 14% for 18th y.o. cohorts) and at Regional Level (+11.2% and +13.5% respectively). Concurrent catch-up of other recommended vaccination for age (diphtheria-tetanus-pertussis-poliomyelitis and papillomavirus), resulted in further increase of doses administered. The fear for meningitis, managed by Sicilian Public Health Authorities, had positive reverberations in terms of prevention. In particular, informative strategies adopted sensibly contributed to get Sicilian young adults closer to vaccination issues.

Objective tools to track medication adherence are lacking. A tool to monitor pill intake that can be implemented in mHealth apps without the need for additional devices was developed. We propose a pill intake detection tool that uses digital image processing to analyze images of a blister to detect the presence of pills. The tool uses the circular Hough transform as a feature extraction technique and is therefore primarily useful for the detection of pills with a round shape. This pill detection tool is composed of two steps. First, the registration of a full blister and storing of reference values in a local database. Second, the detection and classification of taken and remaining pills in similar blisters, to determine the actual number of untaken pills. In the registration of round pills in full blisters, 100% of pills in gray blisters or blisters with a transparent cover were successfully detected. In counting of untaken pills in partially opened blisters, 95.2% of remaining and 95.1% of taken pills were detected in gray blisters, while 88.2% of remaining and 80.8% of taken pills were detected in blisters with a transparent cover. The proposed tool provides promising results for the detection of round pills. However, the classification of taken and remaining pills need to be further improved, in particular for the detection of pills with non-oval shapes.

A topic of growing interest in urban remote sensing is the automated extraction of geometrical building information for 3D city modeling. Roof geometry information is useful for applications such as urban planning, solar potential estimation and telecommunication installation planning, and wind flow simulations for pollutant diffusion analysis. Recent research has proven that the advance in remote sensing technologies and deep learning methods offer the prospects of deriving the roof structure information accurately and efficiently. In this study, we propose a Vectorized Roof Extractor- method based on Fully Convolutional Networks (FCNs) and advanced polygonization method to extract roof structure from aerial imagery and a normalized Digital Surface Models (nDSM) in a regularized vector format. The roof structure consists of building outlines, external edges of the building roof, inner rooflines, internal intersections of the main roof planes. The methodology is comprised of segmentation, vectorization and post-processing for outer rooflines, external edges of the building roof, and inner rooflines, and internal intersections of the main roof planes. For the comparison, we adapt the Frame field Learning (FFL) method originally designed to extract building polygons [1]. Our experiments are conducted on a custom data set derived for the city of Enschede, The Netherlands, using aerial imagery, nDSM and manually digitized training polygons. The results show that the proposed Vectorized Roof Extractor outperformed adapted FFL on PoLiS distance with values of 3.5 m and 1.2 m for outlines and inner rooflines, respectively. Furthermore, the model surpassed the adapted FFL on PoLiS-thresholded F-score for outlines and inner rooflines, with 0.31 and 0.57, respectively. The Vectorized Roof Extractor produced adequate visual results, with straighter walls and fewer missed inner roofline detections. It can predict buildings with common walls thanks to skeleton graph computation. To summarize, the proposed method is suitable for urban applications and has the potential to be improved further.

Sugarcane plays a crucial role in global sugar and ethanol production. Conventionally, sugar-cane propagation involves planting billets. However, Brazilian researchers have introduced the innovative pre-sprouted seedlings (PSS) method, widely used in the MEIOSI (Simultaneously Occurring Interrotational Method) system. Although MPB has several advantages over the con-ventional method, its sensitivity to water scarcity is a challenge. The study aimed to evaluate the survival and growth of PSS inoculated with Bacillus licheniformis and Bacillus subtilis under differ-ent water regimes. The experiment was conducted in the field in a randomized block in strips (split-block) using a 2×4 factorial scheme consisting of two inoculation conditions (with and without bacteria) and four water regimes (0%, 33%, 66%, and 100% of the ideal irrigation). The bacteria increased the PSS's survival and water use efficiency in the field. In addition, inocula-tion increased root and shoot growth, as well as the nutrient uptake such as N, P, Mn, Zn, and Cu, which resulted in a higher number of stalks per meter and, therefore, a higher multiplica-tion rate in the MEIOSI system. Inoculation proved to be a promising alternative for establishing PSS under water restriction.

The efficient and sustainable management of hospitals is an increasingly relevant challenge in the healthcare sector. With limited financial resources, regulatory pressures and increasing demands for quality services, hospitals are faced with the want to approve sound policies to certify financial and operational sustainability. Management accounting is critical in this instance. In Portugal the DL nº 284, of July 26, 1999, allow us to confirm the need to reinforcement of profitability and efficiency in the provision of healthcare. Management accounting is an essential tool for monitoring and controlling costs, making strategic decisions, efficiently allocating resources and evaluating performance in the hospital environment. It allows a comprehensive view of financial and operational aspects, providing valuable information for management and strategic planning. However, the sustainability of hospital management accounting is a critical and complex topic that deserves special attention. Hospitals face several challenges, such as the complexity of hospital costs, the integration of information systems and the measurement of healthcare value. These challenges can compromise the effectiveness of management accounting and its ability to provide relevant and reliable information for decision making. As a result, it is required to address the sustainability of hospital management accounting by identifying the specific challenges faced in this area and exploring opportunities to overcome them. By addressing these challenges and seizing opportunities, hospitals can strengthen their position in the healthcare sector, improve their operational efficiency, optimize resource allocation and ensure the provision of quality services to patients. In this article, the challenges faced by hospital management accounting will be analysed, such as the complexity of costs, the integration of information systems and the measurement of value in healthcare. Additionally, opportunities to improve financial and operational management will be highlighted through the adoption of advanced technologies, an emphasis on value-based management and collaborative partnerships. By exploring these themes, this essay aims to make a contribution. to the advancement of hospital management accounting and the sustainability of hospitals in the current healthcare scenario.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

Background: The 2021 “Universal Definition of Heart Failure (HF)” Proposed the following left ventricle ejection (LVEF) phenotype classification: ≤40%; HF with intermediate LVEF: between 41-49% and HF with preserved LVEF: ≥50%. LVEF represents the percentage of left ventricular ejected volume in each cardiac cycle and Cut-points considered statistically normal are: ≥52% in men and ≥54% in women. The prevalence HFpEF is of 35-60% among the HF phenotypes, with a facing to increase rates in relation to HFrEF and is associated with mortality rates similar to those of HFrEF. The pathophysiology of HFpEF is based on vascular and metabolic dysfunction, therefore, there is less neurohumoral stimulation compared to HFrEF. Methodology: A systematic review was performed to report of information related to Sacubitril-valsartan and the treatment of HFrEF. Terms related to “treatment” and “brazil” were used in the databases PubMed (MEDLINE) and Scientific Electronic Library Online (SCIELO). Results: Clinical trials testing drugs that modulate the neurohumoral system in patients with HFpEF failed to demonstrate benefit in the combined endpoint of reduced mortality/hospitalization due to HF compared to placebo to date. Sacubitril-valsartan is a drug with a mechanism of action surrogate the pathophysiological concept of HFpEF, it is safe and decreased endpoints of natriuretic peptides and left atrial structure in a phase II clinical study. Conclusions: The PARAGON-HF trial demonstrated that sacubitril-valsartan reduced the primary endpoint of the study when assessed the pre-specified subgroup of LVEF≤57% and improved the secondary endpoints of performance status and renal function in the population.

Dye-containing effluent generated in textile industries is polluting and complex wastewater. It should be managed adequately before the final destination. The up-flow anaerobic blanket (UASB) reactor application is an eco-friendly and cost-competitive treatment. The present study briefly reviews the UASB application for dye wastewater valorization. Bioenergy and clean water production potential during dye-containing wastewater treatment are emphasized to promote resource recovery in textile industries. Efficiencies of color and chemical oxygen demand of 50–97% and 60–90% are reported in bench-scale UASB studies. A biogas yield of 0.36–36.04 L d-1 in UASB, which treats dye-containing effluents, is documented. Bioenergy production and water reuse allow environmental and economic benefits. However, data on full-scale UASB treating dye wastewater are missing. Besides, studies on combined systems integrating membrane processes, such as ultrafiltration and nanofiltration, and pretreatment of wastewater and sludge for improvements in biogas production might realize the complete potential for resource recovery of UASB technology.

The objective was to assess the instrumental validity and the test-retest reliability of a low-cost hand-held push dynamometer adapted from a load-cell based hanging scale (tHHD) to collect compressive forces in different ranges of compressive forces. Three independent raters applied 50 pre-established compressions each on the tHHD centered on a force platform in 3 distinct ranges: ~70 N, ~160 N, ~250 N. Knee isometric strength was also assessed on 19 subjects in two sessions (48h apart) using the tHHD anchored by an inelastic adjustable strap. Knee extension and flexion were assessed with the participant seated on a chair with the feet resting on the floor, knees, and hips flexed at 90°. The isometric force peaks were recorded and compared. The ICC and the Cronbach’s α showed excellent consistency and agreement for both instrumental validity and test-retest reliability, as the correlation and determination coefficients. The SEM and the MDC analysis returned adequate low values with a coefficient of variation less than 5%. The Bland-Altman results showed consistency and high levels of agreement. The tHHD is a valid method to assess the knee isometric strength, showing portability, cost-effectiveness, and user-friendly interface to provide an effective form to assess the knee isometric strength.

This paper proposes an upper bound for mine productivity and also a simple truck dispatch rule that demonstrates how tight the upper bound can be using simulation. It also proposes a greedy search to approximate the productivity upper bound, which is faster and often exact. Uncertainty is added to the simulation in order to verify how the productivity responds to it. Typically, the productivity upper bound is less tight close to its saturation point as a function of the number of trucks, where adding more trucks only increases queues. Furthermore, more uncertainty in the model typically leads to a less tight upper bound. The results are conducted using real data from an open pit mine in Brazil.

This paper presents a framework for the motion planning and control of redundant manipulators with the added task of collision avoidance. The algorithms that were previously studied and tested by the authors for planar cases are here extended to full mobility redundant manipulators operating in a three-dimensional workspace. The control strategy consists of a combination of off-line path planning algorithms with on-line motion control. The path planning algorithm is used to generate trajectories able to avoid fixed obstacles, detected before the robot starts to move; it is based on the potential fields method combined with a smoothing interpolation that exploits Bézier curves. The on-line motion control is designed to compensate for the motion of the obstacles and to avoid collisions along the kinematic chain of the manipulator; it is realized by means of a velocity control law based on the null space method for redundancy control. A term of the control law takes into account the speed of the obstacles as well as their position. In order to test the algorithms, a set of simulations are presented: the robot KUKA LBR iiwa is controlled in different cases, where fixed or dynamic obstacles interfere with its motion. Simulations are also used to estimate the required computational effort in order to verify the transferability to a real system.

Secure attachment, developed through consistent relationships with attachment figures in childhood, is a crucial factor in fostering healthy interpersonal relationships and a positive self-perception. This research aimed to assess how perceived security, as an indicator of secure attachment, predicts adult self-concept through the mediating effects of resilience and positive self-esteem. A quantitative, cross-sectional, and non-probabilistic study was conducted with 383 participants, of whom 76.2% were females, aged between 17 and 86 years (M = 28.52, SD = 12.23). Correlational analyses revealed significant positive associations between perceived security, self-concept, resilience, and positive self-esteem. Path analysis demonstrated that resilience and positive self-esteem sequentially mediate the relationship between perceived security during childhood and adult self-concept (Total Effect R2 = .34, F(1,381) = 193, p < .001; Indirect effect of sequential mediation b = .02, CI 95% [.01, .04]). Findings suggest that the ability to cope with ad-versity and personal acceptance underlie the impact of perceived security on self-concept. It is recommended to promote not only secure attachment in family interventions but also resilience and self-esteem in programs targeting adolescents, youth, and adults.

Adaptive Cruise Control (ACC) is useful in the most dangerous maneuvers such as braking and acceleration. This study assesses how ACC modifies traffic flows by analysing the differences be-tween manual and autonomous driving in connected and autonomous vehicles (CAVs). Using a platoon of 80 vehicles, tested in pairs on the road, it was possible to define the speed trends during braking and acceleration and the reaction times to the driving maneuvers (PRT, TH, TCC) with a kinematic data detector. The interactions between the CAV and the driver, have been studied in-novatively, i.e through gaze analysis. Situations of potential danger, characterized by the braking of the vehicle that precedes the car with the driver equipped with the eye tracker tool, have been recreated, considering the influence of the driver’s ACC experience. Results statistically confirmed that with the ACC switched on the reaction times are greater than manual driving (2.4/3.8 sec); this can lead to a reduction in road safety, further motivated by the rapid decrease in speed. The interpolation between automated and human data, finally, has allowed the detection of some criticalities of the system that are fundamental in order to reach the second level of automation.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

In this study the effects of three different main preparatory tillage operations [ploughing at 0.4 m (P40) and 0.20 m (P20) depth and minimum tillage at 0.20 m depth (MT) each of them carried out at two different soil water contents (WC) [low, 58% (LH) and high, 80% (HH) of field capacity] were investigated. The results obtained in this research show high values of soil strength in term of Penetration resistance (CI) and shear strength (SS) particularly in deeper soil layers at lower water content. Fossil-fuel energy requirements both for P40 LH and P20 LH were 25 and 35% higher with respect to the HH treatments and tractor slip were very high (P40 LH = 32.4%) with respect to the P40 HH treatment (16%). Therefore soil water content had significantly influenced tractor performance during soil ploughing, particularly at 0.40 m depth while MT was not influenced at all. A significant correlation between grain yield and soil penetration resistance was found highlighting how soil strength may be good indicator of its productivity. Obtained results during these field tests allowed considering MT and P20 treatments more suitable for this type of soil in climate change scenarios.

Background: The use of barbed sutures for pharyngoplasty techniques is a new trend in sleep apnea surgery, but little is known about its short-term results depending on the different techniques. The objective of this study was to compare the surgical results in two different centers using barbed sutures in which the main difference was the loops performed in the soft palate. Methods: This is a retrospective study of patients with obstructive sleep apnea (OSA) operated in two centers. A statistical analysis comparing the ENT department of the Ospedale Morgagni-Pierantoni from Forlí with the ENT department of Dr. Peset University Hospital was performed. Results: The final sample size was 138 patients (70 from Forlí and 68 from Valencia). In both series, a significant improvement was observed in OSA patients with significant reductions in respiratory events not related to weight reduction. The mean delta Apnea-Hypopnea index was 13.36 (SD 21.3) in Forlí and 22.8 (SD 22.05) in Valencia (p<0.05). Forlí’s series had a higher proportion of multilevel surgeries than Valencia's and a lower proportion of tonsillar hypertrophy. Conclusion: The number of loops performed in the soft palate may improve the surgical results, nevertheless, this must be confirmed in prospective studies.

In the discussion on environmental policies, the notion of eco-efficiency is often used. Eco-efficiency is defined as the delivery of products and services with competitive values, while reducing the ecological impacts and satisfying human needs. In an environment of great competitiveness in which the companies operate, the improvements in the productive process is one of the differentiating factors for guaranteeing a strong competition. Also it is essential rationalizing energy consumption and natural resources. For this it is necessary to understand the main operations and dynamics of the company. This work presents an empirical study of a Portuguese company in the industrial sector. The problematic here presented is based on the company’s growing concern to reduce the amount of scrap produced. From the literature research that was performed, a strong dependence relation between the different variables in the extrusion process was found. The main objective of this work is to model the aluminium extrusion process, with the aim of minimizing the production of scrap. For this several variables involved in the process are taking into account. Using statistical techniques, in particular multiple linear regressions, it was possible to identify the importance of the variables under study for the scrap production.

The present work reports an experimental thermodynamic study of two nitrogen heterocyclic organic compounds, fenclorim and clopyralid, that have been used as herbicides. The sublimation vapor pressures of fenclorim (4,6-dichloro-2-phenylpyrimidine) and of clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) were measured, at different temperatures, using a Knudsen mass-loss effusion technique. The vapor pressures of both crystalline and liquid (including supercooled liquid) phases of fenclorim were also determined using a static method based on capacitance diaphragm manometers. The experimental results enabled accurate determination of the standard molar enthalpies, entropies and Gibbs energies of sublimation for both compounds and of vaporization for fenclorim, allowing a phase diagram representation of the (p,T) results, in the neighborhood of the triple point of this compound. The temperatures and molar enthalpies of fusion of the two compounds studied were determined using differential scanning calorimetry. The standard isobaric molar heat capacities of the two crystalline compounds were determined at 298.15 K, using drop calorimetry. The gas phase thermodynamic properties of the two compounds were estimated through ab initio calculations, at the G3(MP2)//B3LYP level, and their thermodynamic stability was evaluated in the gaseous and crystalline phases, considering the calculated values of the standard Gibbs energies of formation, at 298.15 K.

Scientific studies had shown that mixed forests of silver fir (Abies alba Mill.) and European beech (Fagus sylvatica L.) provide higher ecosystem services than monospecific forests. Mixed forests are known for their high resilience to climate change impacts and superior biodiversity compared to monospecific forests. In many countries, promotion of mixed forests in forest management is becoming a government policy since they can contribute to fulfill the Sustainable Development Goals set by the United Nation, respectively Goal 13 and 15. However, not much is known about public perceptions on mixed forests compared to monoculture forests. Our study on ecosystem services provided by mixed and monospecific forests in southwest Germany fill this gap. Based on a survey with 520 valid responses we analyzed people’s perception on 18 different supporting, cultural, regulating and provisioning ecosystem services measured by Likert scale. Stepwise regression analyses show relations between social profiles (gender, age, education, profession) and preferences on respondents’ perceptions. Our findings show that people perceive that mixed forests provide better cultural, regulating and supporting ecosystem services than monospecific forests of fir and beech whereas provisioning services were perceived as being equally or better provided by monospecific forests. Significant effects towards a positive perception on ecosystem services provided by mixed forests were mainly influenced by the perceived abundance of old trees, feeling of pleasantness in mixed forests, age, profession, and education. Our findings indicate that there is a high public support for the promotion of silver fir and beech mixed forests in Southwest Germany.

In our increasingly urbanized world, precise and up-to-date maps of human settlements are essential for sustainable urban development policies. The availability of open-access Sentinel-2 data from the Copernicus program presents an opportunity to create a comprehensive global map of human settlements, offering a detailed view of built areas on a large scale. This study estimates large-scale built-up fractions using encoder-decoder deep learning architectures like U-net, Res-U-net, and Attention-U-net in the large and complex urban area of Delhi, India. Openly available datasets like Open Street Map (OSM) and Microsoft building footprint datasets are used to derive built-up fractions at 10×10m resolution cells for over 34,000 km2. Our results show that Attention-U-net with the Huber loss function performs the best in different built-up densities (i.e., urban, semi-urban or rural) with an R2 score of 0.631, while Res-U-net and U-net obtained an R2 score of 0.623 and 0.612, respectively. The investigated networks significantly improve the accuracy over the latest Global Human Settlement Layer product (GHSL-S2), which uses a deep-CNN and reaches an R2 of 0.387 in our case study area. The result of this study yields a valuable spatial layer for examining the spatial distribution of human settlements across the entire spectrum from rural to urban areas.

Ozonated oil has several benefits for humans, as it contributes to numerous interventions, maintaining the quality of life and the well-being of individuals. Being a natural product, it has few or almost no side effects. Thus, the study aimed to verify the sensitivity and/or resistance of fixed o “Ozonated” and “Non-Ozonated” oils from Mauritia flexuosa (Buriti), Carapa guaianensis (Andiroba) and essential “Ozonated” oils from Menta piperita (Mint), Eugenia caryophyllus (Clove) in different concentrations, against internationally known bacteria from the American Type Culture Collection – ATCC, comparing with the “Non-Ozonated” versions of the respective oils, using the Agar diffusion technique. Thus, it is evident that the ozonation of the fixed oils of Buriti and Andiroba, as well as the essential oils of Mint and Clove, provided significant results, although they were statistically different. The Buriti and Andiroba oil were ineffective in inhibiting microorganisms. On the other hand, the essential oil of Mint and Clove obtained similar activity of inhibition of microorganisms. With regard to Ozonation, the Essential Oil of “Ozonated” Clove provided greater activity than the “Non-Ozonated” one, which inhibited only one tested microorganism, in addition to producing changes in its chemical composition, requiring individualized studies for the ozonation of each essential oil.

Species distribution models (SDMs) are usually used to predict current species’ geographic distributions and to forecast the impact of climate change, with different aims, such as conservation, and biodiversity management. SDMs use has been increasing in the last decades, however, they are vulnerable to parametrization and data quality input. Thus, inappropriate input can lead to potential unreliability in results. In this context, the most used data and methodologies in SDM, and putative deviations from the consensual best practices, were identified, by analysing recent literature (2018 to 2022). Results show that the parameters presented more consistently are the chosen algorithm (MaxEnt was used in 98% of the studies), the accuracy measures, and the time windows. Many papers fail to specify other parameters, limiting the reproducibility of the studies. Some papers also fail to provide information about the target species: only a fraction of the species' range is considered, or no justification for including specific variables in the model is provided. These options can decrease reliability in predictions under future scenarios since data provided to the model is inaccurate from the start or there is insufficient information for outputs discussion.

In its Nationally Determined Contribution (NDC) to the United Nations Framework Convention on Climate Change, Brazil committed to reducing greenhouse gas emissions and restoring its forests. This study examines the challenges of fulfilling these commitments in Brazilian Amazonia. We carry out a detailed assessment of the current status of land tenure in the region and its relation to deforestation. After dealing with conflicts and overlaps between data from various sources, we produce a new map of public and private land tenure in Amazonia. Combining this map with Brazil's official data on deforestation, we find out how much natural vegetation has been preserved in each public or private area. The result is used to estimate how much deforestation is illegal. We also establish how much deforestation is associated with each land tenure type. Our results show that most deforestation inside rural properties is done by a few landowners, a finding that has important consequences for law enforcement. We then assess the challenges for reforestation in detail. To do so, we consider how much forest needs to be rehabilitated according to Brazil's Forest Code. Our analysis provides a comprehensive appraisal of the potential opportunity costs for forest restoration in the biome, considering farm size and land use. This analysis provides insights into targeted land use policies that can meet Brazil’s forest restoration goals.

Portugal’s EPAC silo network, initially planned in the 1930s but constructed and utilized primarily in the 1970s, consisted of 31 silos with a total capacity of 841,100 t. The network’s usage declined, however, due to market liberalization and Portugal’s accession to the European Economic Community in 1985. This study focuses on adapting a methodology to inventory and analyse the 31 silos in the EPAC network considering their general features, construction, technological facilities, and socioeconomic aspects. The silos are situated in 30 cities and towns, predominantly in the country’s key grain-growing regions, particularly the Alentejo region. While there are variations in design and construction, most EPAC silos contain two or three rows of circular reinforced-concrete cells and use the spaces between cells for storage. Their capacities range from 6,000 to 35,000 t. Some are inland grain reception and storage silos, while others are larger-capacity port silos designed to unload grain rapidly onto ships using mechanical or pneumatic unloaders. These structures are a significant part of Portugal’s agro-industrial heritage and have in some cases been repurposed as museums or event venues. Compared to other agro-industrial buildings, silos pose unique conversion challenges due to their height and design complexities. Examples of successful reuse in countries like Spain and Italy may provide insights for potential silo projects in Portugal. However, analysis suggests that such proposals and similar initiatives may be viable only in the more highly populated towns.

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile and non-destructive inference of transverse beam quality (emittance) using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded in to adaptive feedbacks and ML-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results based on simulation data and discuss progress towards implementation in regular operations.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

As use of composite materials increases, the search for suitable automated processes gains relevance to guarantee production quality by ensuring uniformity of the process, minimizing the amount of generated scrap and reducing time and energy consumption. Limitations on production by traditional means such as hand lay-up, vacuum bagging and in-autoclave methods, tend not to be as efficient when the size and shape complexity of the part being produced increases, motivating the search for alternative processes such as the Automated Tape Laying (ATL). This work aims to describe the process of modelling and simulating a composite ATL with in situ consolidation by characterizing the machine elements, using the finite differences method in conjunction with energy balances, in order to create a digital twin of the process for further control design. The modelling approach implemented is able to follow the process dynamics when changes to the heating element are imposed as well as to predict the composite material temperature response, making it suitable to work as a digital twin of a production process using an ATL machine.

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte i.e. proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included in the model. It can be regarded as a kind of "minimal'' model in the sense that contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase, and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 to low pH-values (Pincus regime), is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

Qualtra, an innovative 10 MW geothermal power plant proposal, employs a closed-loop design to mitigate emissions, ensuring no direct release into the atmosphere. A thorough assessment utilizing energy and exergy analysis, Life Cycle Assessment (LCA), Exergo-economic and Exergo Environmental Analysis (EevA) was conducted. The LCA results, utilizing the ReCiPe 2016 midpoint methodology, encompass all the spectrum of environmental indicators provided. The technology implemented makes it possible to totally avoid direct atmospheric emissions from the Qualtra plant, so the environmental impact is mainly due to indirect emissions over the life cycle. The results obtained for the Global Warming Potential indicator is about 6.6 g CO2/kWh, notably lower compared to other conventional systems. Contribution analysis reveals that the construction phase dominates, accounting for over 90% of the impact in all LCA MidPoint categories. At the component level, a single score calculation incorporating normalization and weighting was executed. The resulting single score is then used into Exergo-Environmental Analysis (EEvA), highlighting the well system as the most impactful contributor, constituting approximately 45% of the total impact. Other substantial contributions to the environmental impact include the condenser (21%), the turbine (17%), and the HEGeo (14%). The Exergo-Economic analysis assesses cost distribution across major plant components, projecting an electricity cost of about 8.3 c€/kWh.

This study investigated the associations of imageability with fear reactivity. Imageability ratings of four word classes: positive and negative (i) emotional and (ii) propriosensitive, neutral and negative (iii) theoretical and (iv) neutral concrete filler, and fear reactivity scores – degree of fearfulness towards different situations (TF score) and total number of extreme fears and phobias (EF score), were obtained from 171 participants. Correlations between imageability, TF and EF scores were tested to analyze how word categories and their valence were associated with fear reactivity. Imageability ratings were submitted to recursive partitioning. Participants with high TF and EF scores had higher imageability for negative emotional and negative theoretical words. The correlations between imageability of negative emotional words and negative theoretical words for EF score were significant. Males showed stronger correlations for imageability of negative emotional words for EF and TF scores. High imageability for positive emotional words was associated with lower fear reactivity in females. These findings were discussed with regard to negative attentional bias theory of anxiety, influence on emotional systems, and gender-specific coping styles. This study provides insight into cognitive functions involved in mental imagery, semantic competence for mental imagery in relation to fear reactivity, and a potential psycholinguistic instrument assessing fear tendency.

Lymphedema is a chronic and debilitating disease that affects up to 250 million patients worldwide. Recent advances in understanding its pathophysiology, along with improved diagnosis and microsurgical techniques, have enhanced our ability to cope with the challenging task of treating this disease. This review provides an overview of the disease from a surgeon's point of view, including existing imaging modalities used for preoperative assessment, as well as surgical procedures used in its treatment. Advantages and drawbacks of various existing modalities used for pre or intraoperative assessment of lymphatic vessels are discussed. Lymphedema treatment has shifted from palliative debulking procedures (liposuction and direct excision) to those aimed at restoring lymphatic flow and countering the pathophysiology of the disease (lymphaticovenous anastomosis and vascularized lymph node transfer). A combination of both approaches can result in a synergistic benefit for patients and are discussed in this review. Despite recent advances, some controversies persist, and further studies are needed to better define surgical treatment algorithms.

TomoSim comes as part of project ATMOS, a miniaturised DOAS tomographic atmospheric evaluation device, designed to fit a small drone. During the development of the project, it became necessary to write a simulation tool for system validation. TomoSim is the answer to this problem. The software has two main goals: to mathematically validate the tomographic acquisition method; and to allow some adjustments to the system before reaching final product stages. This measurement strategy was based on a drone performing a sequential trajectory and gathering projections arranged in fan beams, before using some classical tomographic methods to reconstruct a spectral image. The team tested three different reconstruction algorithms, all of which were able to produce an image, validating the team’s initial assumptions regarding the trajectory and acquisition strategy. All algorithms were assessed on their computational performance and their ability for reconstructing spectral "images", using two phantoms, one of which custom made for this purpose. In the end, the team was also able to uncover certain limitations of the TomoSim approach that should be addressed before the final stages of the system.

Accurate channel estimation is of utmost importance for massive MIMO systems that allow providing significant improvements in spectral and energy efficiency. In this work, we investigate the spectral efficiency performance and present a channel estimator for multi-cell massive MIMO systems subjected to pilot-contamination. The proposed channel estimator performs well under moderate to aggressive pilot contamination scenarios without prior knowledge of the inter-cell large-scale channel coefficients and noise power. The estimator approximates the performance of a linear Minimum Mean Square Error (MMSE) as the number of antennas increases. Following, we derive a lower bound closed-form spectral efficiency of the Maximum Ratio Combining (MRC) detector in the proposed channel estimator. The simulation results highlight that the proposed estimator performance approaches the linear minimum mean square error (LMMSE) channel estimator asymptotically.

Advanced-Differential Interferometric SAR (A-DInSAR) has been used to monitor surface deformations in open pit mines and tailings dams. In this paper, ground deformations have been detected on the area of the tailings Dam-I at the Córrego do Feijão Mine (Brumadinho, Brazil) before its catastrophic failure occurred on 25 January 2019. Two techniques optimized for different scattering models, SBAS (Small BAseline Subset) and PSI (Persistent Scatterer Interferometry), were used to perform the analysis based on 26 Sentinel-1B images in IW mode, acquired on descending orbits from 03 March 2018 to 22 January 2019. A WorldDEM DSM product was used to remove the topographic phase component. The results provided by both techniques showed a synoptic and informative view of the deformation process affecting the study area, with a detection of persistent trend of deformations on the top, middle and bottom sectors of the dam face until its collapse, as well as the expected natural settlements on the tailings. It is worth noting the detection of an acceleration in the displacement time-series for a short period near the failure. The maximum accumulated displacements detected along the downstream slope face were -39 mm (SBAS) and -48 mm (PSI). It is reasonable to consider that Sentinel-1 would provide decision makers complementary motion information to the in-situ monitoring system for risk assessment and for a better understanding of on-going instability phenomena affecting the tailings dam.

Aging is a complex biological process, with gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging, vary with sex, in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in renal cortex, α-smooth muscle actin (α-SMA) and fibronectin, was evaluated in male and female rats aged 3 and 18 months submitted or not to water deprivation (WD) for 48 hours. When comparing ages, 18-month-old males showed lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-moth-old male and female rats exhibited higher expression of α-SMA than respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than respective 3-month-old males. In females, only control 18-month-old rats showed higher fibronectin than control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had lower expression of Slc12a3 mRNA than re-spective males. WD 18-month-old male rats presented higher expression of fibronectin and α-SMA than WD 18-month-old female rats. When we compared hydric condition, WD 18-month-old males displayed lower relative expression of Slc12a3 mRNA and higher α-SMA expression than control 18-month-old males. Aging, sex, and dehydration lead to alteration in kidney structure.

This study explores the integration of Artificial Intelligence (AI) and collaborative robotics in industrial surface finishing, focusing on feature detection on object reflective surfaces using neural networks in computationally constrained environments. Central to this investigation is the utilization of cameras considered as sensors that can capture detailed images of reflective surfaces. These images are then analyzed by a custom neural network, demonstrating the feasibility of feature detection with non-powerful computers. The public dataset for recognizing light reflection defects, available in the SPADD repository, supports this approach. Employing open-source tools like Darknet YOLOv3 and Yolo\_mark, this method proves particularly advantageous for small and medium-sized enterprises (SMEs) due to its low cost and maintenance requirements. This research highlights the challenges of AI and collaborative robotics in industrial applications, especially in adapting to varying conditions and the need for continuous training with new data coming from several sensors. Looking ahead, plans are in place to integrate this system with cobot-assisted polishing tasks, using cameras to enhance manufacturing efficiency and quality. This work contributes to the broader understanding of practical applications of AI in industrial automation, surface finishing processes, and the effective use of sensor technology.

MAD is the gold standard therapy for mild/moderate OSA and is a second-choice treatment in patients with severe OSA not responding to CPAP. The aim of this study was to analyze the upper airway characteristics of OSA patients and the morphological changes in the upper airway, inducted by four different types of mandibular advancement devices, using CBCT 3D imaging. Twenty-two patients were recruited after OSA diagnosis with polysomnography. Four different customized and titratable MAD were used and an initial CBCT scan was obtained for each patient. After 6 months to the end of the MAD titration phase, all the subjects showed an AHI of &lt; 5 or a decrease of 50% in AHI with MAD when compared with initial AHI and a second CBCT scan with MAD in situ was performed. An important improvement of the airway was observed (+33.76%) and a significant difference in the enlargement ratio between the posterior soft palate (+32.41%) and the posterior tongue (+36.96%) region was also found. The greatest increase in airway volume was achieved in patients treated with the MAD Forward and TAP (respectively +42.77% and + 41.63%). MAD therapy is effective to treat mild/severe OSA with increased upper airway volume. The design of the MAD can influence the effectiveness of the treatment.

Comminution is the most power-demanding stage, and the lack of geometallurgical testing, often for financial reasons, may result in an inefficient operation. The Geopyörä Rock Breakage test was developed with the objective of making mineral variability data more accessible by providing both standard comminution parameters and rock mechanical properties at low cost, and with a modest sample size, allowing a larger number of samples to be tested to reduce uncertainties and assure productivity. The objective of this work is to present the results of an extensive validation of this new rock breakage method against two of the main tests currently in use, namely the SMC® and Bond ball mill work index tests. More than 100 samples have been tested and the results compared, showing that the new method can accurately estimate the parameters of the traditional tests. This confirms that the new test is a reliable tool for comminution and geometallurgical tests.

In no-tillage systems, there is an accumulation of crop residues (CR) which plays an important role in available of soil-N. A study was set up to provide information regarding the CR N credit, and the influence of N mineral fertilizer. An incubation was run in a loam soil with addition of a similar rate of residue (10 Mg ha-1; sugarcane, soybean, and brachiaria) and N mineral fertilizer (urea; 120 kg N ha-1). After the stabilization of biological activity, soil and remaining residues were collected, and N monitored. Results showed that the N credit was positive with application of soybean, sugarcane, and brachiaria. There was an expressive performance of soybean N credit represented by a positive balance, and a reduction from 2.49 to 0.9 g kg-1 of N in residue, with direct increase of 90% of soil-N. There is no need of N fertilizer to potentialize the soybean N credit, but it is requested to potentialize N credit of brachiaria and sugarcane. The urea demonstrated be a good enhancer of brachiaria N credit, but it was not adequate to sugarcane residues. Based in our result, the accumulation and incorporation of CR can be considered as a N credit with positive contribution in soil-N.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Antimicrobial resistance (AMR) has a significant global impact on human, animal, and environmental health. Misuse and overuse of antibiotics in clinical and animal production settings are the main drivers behind the emergence of antimicrobial resistant bacteria. However, other compounds with antimicrobial activity may also contribute to this global public health problem. The aim of this comprehensive review is to provide detailed insights into the impact of metals and organic acids on the emergence and spread of AMR in the food chain, for which their role is not fully understood. The review examines the widespread use of organic acids in the food industry as feed additives or disinfectants, the crucial role of copper in animal growth and the harmful effects of mercury and arsenic as pollutants in food-producing environments. Additionally, it explores the antimicrobial mechanisms of metals and organic acids, the tolerance mechanisms developed by bacteria, and the interplay between genes responsible for metal tolerance and AMR. The comprehensive and integrated data presented highlights the need to further explore and understand the role of metals and organic acids as drivers of AMR to develop well-defined strategies effectively mitigating the AMR crisis within the food chain context.

Background: This study aimed to evaluate survival rate, marginal bone levels, and full arch prosthetic success on short implants when placed in areas of severely resorbed and edentulous mandibles. Methods: This is a systematic review of all randomized controlled trials of at least 10 patients with a control group in which bone augmentations were performed that were published between January 2010 and February 2023. Only 3 relevant studies met the inclusion criteria. Results: It obtained demonstrate that short-term dental implant survival rates ranged from 94.2% to 97.4% with a 5-year follow-up and the prosthetic success rate varied by 62% during the same follow-up. The mean marginal bone level values ​​of the affected short implants ranged from 0.2 mm to 0.6 mm. Conclusions: The data obtained demonstrated that short dental implants positioned with criterion and precision as a full-arch fixed support are a valid therapeutic choice for the medium-long term rehabilitation of severe edentulous mandibular atrophy.

Cutaneous T-cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at a clinical and therapeutic level regarding the most well-known inflammatory mediators. An in-depth look has been given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression.From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major Interleukins known in inflammatory environments.Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL.In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.

Fires in houses are inevitable and they cause loss of life and major repair costs for the damage structure and contents. There is a clear need to prevent its ignition and spread to adjacent areas. This article presents the steps taken, namely: contacts, data collection, tests, analysis and conclusions regarding the accident resulting from the outbreak and spread of a fire, on December 25, 2020, in a traditional Portuguese house in Arganil, Portugal. The owners and the court requested to carry out an expert opinion by a person with specialized technical-scientific knowledge, which led to this work as an expert. the work consists of carrying out observations and data analysis. Then, the observed and analysed data were laboratory tested in order to consistently identify characteristics that lead to the ignition and propagation of the fire. This work identified construction problems, materials used and heat sources that are responsible for the accident. The conclusions may be used to avoid future incidents or accidents with houses of same construction type.

The environmental Kuznets curve (EKC) hypothesis posits an inverted U-shaped relationship between economic growth and environmental degradation. However, there is no consensus regarding the EKC hypothesis among countries and regions of different income groups. In this study, we analyze the EKC hypothesis for 158 countries and 44 regions from 1990 to 2020, categorizing them into different income groups based on the World Bank's income classification (low, lower-middle, upper-middle, and high-income countries). Our findings reveal mixed patterns in the EKC across different income levels, highlighting the heterogeneous relationship between economic growth and carbon emissions and showing differentiated patterns among different income levels. While a rise in income for high-income countries should be reflected in a shift toward fewer carbon emissions, for lower-income countries, growth is still associated with rising emissions. This underscores the urgent need for policy interventions that decouple economic development from environmental degradation. A balanced approach to economic growth, which prioritizes carbon neutrality across all stages of development, by tailoring environmental and economic strategies to address CO2 emissions effectively, should be adopted, recognizing the different developmental stages and income levels of countries and regions.

This paper provides a comparative study between microwave tomography and synthetic time-reversal imaging techniques as applied to ground penetrating radar (GPR) surveys. The comparison is carried out by processing experimental data collected at a controlled test site, with various types of buried targets at given subsurface depths and representative soil conditions. It is shown that the two techniques allow us to obtain complementary information about position, depth and size of the targets from a single GPR survey.

Biodiesel is seen as a successor to diesel of petrochemical origin, as it can be used in cycle engines and stationary engines, and be obtained from renewable raw materials. Currently, the biodiesel production process on an industrial scale is mostly carried out through the transesterification reaction, also forming glycerol as a product. Pure glycerol is used in the pharmaceutical, cosmetic, cleaning, food and other industries. Even presenting numerous applications, studies indicate that there is a saturation of glycerol in the market which is directly related to the production of biodiesel. This increase causes a commercial devaluation of pure glycerol; making the separation and purification processes unfeasible from an economic point of view. Despite the economic unfeasibility of the aforementioned processes, they continue to be carried out due to environmental issues. Faced with the problem presented, this work aims at a bibliographical review of works that aimed to use glycerol as a raw material for the production process of biofuels, these processes being carried out mostly via fermentation.

Background and Aims. Most research on Parkinson's disease (PD) focuses on describing symp-toms and movement characteristics. Studies rarely focus on the early detection of PD and the search for suitable markers of a prodromal stage. Early detection is important, so treatments that may potentially change the course of the disease can be attempted early on. While gait disturb-ances are less pronounced in the early stages of the disease, the prevalence, and severity increase with disease progression. Therefore, postural instability and gait difficulties could be identified as sensitive biomarkers. The aim was to evaluate the discriminatory power of the Trail-Walking Test (Schott, 2015) as a potential diagnostic instrument to improve the predictive power of the clinical evaluation concerning the severity of the disease and record the different aspects of walking. Methods. 20 older healthy (M = 72.4 years, SD = 5.53) adults and 46 older adults with PD and the motor phenotypes postural instability/gait difficulty (PIGD; M = 69.7 years, SD = 8.68) and tremor dominant (TD; M = 68.2 years, SD = 8.94) participated in the study. The participants performed a motor-cognitive dual task (DT) of increasing cognitive difficulty in which they had to walk a given path (condition 1), walk to numbers in ascending order (condition 2), and walk to numbers and letters alternately and in ascending order (condition 3). Results. With an increase in the cognitive load, the time to complete the tasks (seconds) become longer in all groups, F(1.23, 73.5) = 121, p < .001, ɳ2p = .670. PD-PIGD shows the longest times in all conditions of the TWT, F(2, 60) = 8.15, p < .001, ɳ2p = .214. Mutual interferences in the cognitive and motor domain can be observed. How-ever, clear group-specific patterns cannot be identified. A differentiation between the motor phenotypes of PD is especially feasible with the purely motor condition (TWT-M; AUC = . 685, p = 0.44). Conclusions. PD patients with PIGD must be identified by valid, well-evaluated clinical tests that allow a precise assessment of the disease's individual fall risk, the severity of the dis-ease, and the prognosis of progression. The TWT covers various aspects of mobility, examines the relationship between cognitive functions and walking, and enables differentiation of the motor phenotypes of PD.

Petrochemicals, which convert oil and gas into products such as plastics, are fundamental to modern societies. Chemists recognize their role in the design of materials and the adverse effects that these may have on the environment, preventing sustainable development. Several methodological frameworks and sustainability assessment approaches have been developed to evaluate the resources used in the petrochemical sector in terms of environmental costs. A combination of Life Cycle Assessment and Emergy Accounting - to assess the environmental support for resource use - is applied in this study of the PET production chain in Europe. The Unit Emergy Values of several intermediates are calculated or updated to facilitate discernment of the quality of energy used and the processes' efficiency. Several routes for synthesizing renewable para-xylene and ethylene glycol from biomass are discussed and confronted with the efforts focused on recycling and recovering the final product providing concurrently a procedure and a valuable data set for future CP actions. The results show that understanding the efficiencies changing across the production chain may help stakeholders make wise choices as to where and when interventions to promote a circular economy are most effective along a petrochemical production chain.

Obstructive Sleep Apnea (OSA) surgery is now a viable solution in selected patients and the “remodelling” palatopharyngeal surgery is the most common one. Recently it becomes less in-vasive with the introduction of Barbed Sutures (BS). An optimization of surgical technique is represented by Barbed pharyngoplasty (BP), that requires surgical precision and needs efficient and precise oropharyngeal visualization. Consequently, the lighting system is of pivotal im-portance in BP. The aim of this work is to describe the first experience on the use of a new light-ing system, called KlaroTM in BP for OSA. We evaluated the Klaro™ system in 15 consecutives BP for OSA in comparison with conventional headlamp illumination. The visualization of pala-topharyngeal muscle in the bottom of the tonsillar fossa, entry and exit needle, such as needle tip were statistically better with KlaroTM than headlamp illumination both for surgeon and resi-dent (p<0.05). No significant differences for the visualization of the posterior pharyngeal wall and uvula were reported. The KlaroTM lighting system allows a satisfied illumination of oral cavity and oropharynx in the majority of cases. We encourage to use of KlaroTM not only in BP for OSA, but also in all oral and pharyngeal surgeries, including tonsillectomy and oncological surgery.

Thermal comfort is extremely important in architecture, especially in environments with more people spending longer on studies or intellectual activities. This research describes a case study to investigate university buildings' energy and thermal performance as a part of the ANEEL program. Due to this importance, and the need to save energy in Brazilian public buildings, the ANEEL-the Brazilian Energy Electricity Regulatory Agency, launched 2016 a national program focusing on energy efficiency in public universities around the country. University offices and classrooms require high intellectual effort; thus, environmental comfort is critical for maintaining its users' physical and mental health. This study included a pre-diagnosis of the performance of the envelope, lighting, and air conditioning systems and a survey about the quality of the environments from the users' point of view. The Prescriptive Method of the Brazilian Labeling Program (PBE) for Commercial, Service, and Public Buildings (RTQ-C) assessed the building performance. Statistical analysis was applied to correlate the quality and thermal preference of the users from the PMV/PPD. The results showed a high rate of thermal discomfort in both environments of the studies, even when using air conditioning.

Viral infections inflict many serious human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

Healthcare workers' stress, burnout, and job dissatisfaction were exacerbated by the Covid-19 pandemic, whose mid-term negative effects are still present. The aim of this study was to investigate in healthcare workers the effect of the dimensions of burnout (Psychophysical exhaustion, Relational deterioration, and Professional inefficacy) on Career satisfaction. These relationships were evaluated by considering the direct and mediated effects of Disillusion. For these purposes, the Link Burnout Questionnaire (LBQ) and the Career Satisfaction Scale (Occupational Stress Indicator - OSI) were administered to 295 healthcare professionals working at three Italian public hospitals in Cagliari, Italy. The analyses were conducted using the Partial Least Square Structural Equation Model (PLS-SEM) method. Findings highlight that healthcare workers were in a condition of work distress, high risk of burnout, and career dissatisfaction. Also recognized was the direct negative effect of burnout dimensions on career satisfaction. Finally, the mediated negative effect of Disillusion in the relationship between burnout and career satisfaction was identified. This study emphasizes the relevance of the dimension of Disillusion, and its “bright side” Fulfilment, in healthcare workers, specifically referring to the disregarded relationship between burnout and career satisfaction.

Nerve agents have recently been used in battlefield operations, espionage wars and terrorist attacks. These compounds, like some pesticides, cause organophosphate poisoning. The rapid, non-contact detection of a sarin simulant has been demonstrated at the Diagnostics and Metrology Laboratory of the Italian National Agency for New Technologies, Energy and Sustainable Economic Development using laser photoacoustic spectroscopy, an infrared absorption technology. The first measurements, carried out with an experimental system based on a quantum cascade laser and developed for the assessment of food authenticity in the “fingerprint region”, show that a detection limit of 1 nanolitre is within the reach of the instrument when chemometric analysis is applied.

The inverse Finite Element Method (iFEM) is a model-based technique to compute the displacement (and then the strain) field of a structure from strain measurements and a geometrical discretization of the same. Different literature works exploit the error between the numerically reconstructed strains and the experimental measurements to perform damage identification in a Structural Health Monitoring framework. However, only damage detection and localization are performed, without attempting a proper damage size estimation. The latter could be based on machine learning techniques, however, an a priori definition of the damage conditions would be required. To overcome these limitations, the present work proposes a new approach in which the damage is systematically introduced in the iFEM model to minimize its discrepancy with respect to the physical structure. This is performed with a maximum likelihood estimation framework, where the most accurate damage scenario is selected among a series of different models. The proposed approach is experimentally verified on an aluminum plate subjected to fatigue crack propagation, which enables the creation of a Digital-Twin of the structure itself. The strain field fed to the iFEM routine is experimentally measured with an Optical Backscatter Reflectometry fiber and the methodology is validated with independent observations of lasers and the Digital Image Correlation.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

The central limit theorem (CLT) and its generalization to stable distributions have been widely described in literature. However, many variations of the theorem have been defined and often their applicability in practical situations is not straightforward. In particular, the applicability of the CLT is essential for a derivation of heterogeneous ensemble of Brownian particles (HEBP). Here, we analyze the role of the CLT within the HEBP approach in more detail and derive the conditions under which the existing theorems are valid.