The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion

Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.     

Transient multiphase CO2 release from high-pressure tanks: Influence of phase changes,viscous heating,and Joule–Thomson effect

In this study, CO₂ free expansion from high-pressure tanks is studied in a transient state while considering the influence of different phenomena—that is, viscous heating, phase transition (solid/liquid/vapour phase), and the Joule–Thomson effect—in an initially supersonic flow. This investigation is performed using computational fluid dynamics (CFD) techniques, comparing the obtained results with some experimental data of the literature with a maximum discrepancy of around 8.5%. In particular, for the first time from the literature, it is observed that, according to the velocity evolution at the outlet, the discharge process is conveniently divided into three here-defined stages: (1) shocking flow, where pressure abruptly decreases with time and flow becomes supersonic, this leading to the condensation of part of CO₂; (2) transition flow, characterized by a sort of constant pressure time trend; and (3) flashing flow, where pressure decreases less abruptly following an asymptotic pattern up to the atmospheric one and flow becomes subsonic. Furthermore, non-equilibrium condensation occurring in the tank, tube, and outlet is observed, finding that the minimum temperature reached by the fluid is around 235 K (−38°C). As well, the non-equilibrium condensation is taken into account in order to give an indication of the amount of liquid CO₂ leaving the outlet in the form of high-speed jet, which can be a serious danger for personnel and surrounding installations. Moreover, we observe an important effect of viscous heating in the early-stage expansion for a relatively short time range, within which the temperature in the tube experiences an abrupt increase of around 210 K (from 170 to 380 K). The same effect in the external room creates a convection flow, pushing CO₂ towards the top. The results of the present work can be used for health, safety, and environment (HSE) management purposes and for a more precise process design related to CO₂ storage and sequestration.     

Highly Nonstoichiometric YAG Ceramics with Modified Luminescence Properties

Y₃Al₅O₁₂ (YAG) is a widely used phosphor host. Its optical properties are controlled by chemical substitution at its YO₈ or AlO₆/AlO₄ sublattices, with emission wavelengths defined by rare-earth and transition-metal dopants that have been explored extensively. Nonstoichiometric compositions Y_3+xAl_5-xO₁₂ (x ≠ 0) may offer a route to new emission wavelengths by distributing dopants over two or more sublattices simultaneously, producing new local coordination environments for the activator ions. However, YAG typically behaves as a line phase, and such compositions are therefore challenging to synthesize. Here, a series of highly nonstoichiometric Y_3+xAl_5-xO₁₂ with 0 ≤ x ≤ 0.40 is reported, corresponding to ≤20% of the AlO₆ sublattice substituted by Y³⁺, synthesized by advanced melt-quenching techniques. This impacts the up-conversion luminescence of Yb³⁺/Er³⁺-doped systems, whose yellow-green emission differs from the red-orange emission of their stoichiometric counterparts. In contrast, the YAG:Ce³⁺ system has a different structural response to nonstoichiometry and its down-conversion emission is only weakly affected. Analogous highly nonstoichiometric systems should be obtainable for a range of garnet materials, demonstrated here by the synthesis of Gd_3.2Al_4.8O₁₂ and Gd_3.2Ga_4.8O₁₂. This opens pathways to property tuning by control of host stoichiometry, and the prospect of improved performance or new applications for garnet-type materials.     

Understanding the Interactions of Guanine Quadruplexes with Peptides as Novel Strategies for Diagnosis or Tuning Biological Functions

Guanine quadruplexes (G4s) are nucleic acid structures exhibiting a complex structural behavior and exerting crucial biological functions in both cells and viruses. The specific interactions of peptides with G4s, as well as an understanding of the factors driving the specific recognition are important for the rational design of both therapeutic and diagnostic agents. In this review, we examine the most important studies dealing with the interactions between G4s and peptides, highlighting the strengths and limitations of current analytic approaches. We also show how the combined use of high-level molecular simulation techniques and experimental spectroscopy is the best avenue to design specifically tuned and selective peptides, thus leading to the control of important biological functions.     

From low-level programming to full-fledged industrial model-based development: the story of the Rubus Component Model

Developing distributed real-time systems is a complex task that has historically entailed specialized handcraft. In this paper, we propose a retrospective on the (r)evolutionary changes that led to the transition from low-level programming to industrial full-fledged model-based development embodied by the Rubus Component Model and its tool-ecosystem. We focus on the needs, challenges, and solutions of a 15-year-long evolution journey of a software development approach that has gone from low-level and manual programming to a highly automated environment offering modeling, analysis, and development of vehicular software systems with multi-criticality for deployment on single- and multi-core platforms.

     

Are We There Yet? A Roadmap of Network Visualization from Surveys to Task Taxonomies

Networks are abstract and ubiquitous data structures, defined as a set of data points and relationships between them. Network visualization provides meaningful representations of these data, supporting researchers in understanding the connections, gathering insights, and detecting and identifying unexpected patterns. Research in this field is focusing on increasingly challenging problems, such as visualizing dynamic, complex, multivariate, and geospatial networked data. This ever-growing, and widely varied, body of research led to several surveys being published, each covering one or more disciplines of network visualization. Despite this effort, the variety and complexity of this research represents an obstacle when surveying the domain and building a comprehensive overview of the literature. Furthermore, there exists a lack of clarification and uniformity between the terminology used in each of the surveys, which requires further effort when mapping and categorizing the plethora of different visualization techniques and approaches. In this paper, we aim at providing researchers and practitioners alike with a “roadmap” detailing the current research trends in the field of network visualization. We design our contribution as a meta-survey where we discuss, summarize, and categorize recent surveys and task taxonomies published in the context of network visualization. We identify more and less saturated disciplines of research and consolidate the terminology used in the surveyed literature. We also survey the available task taxonomies, providing a comprehensive analysis of their varying support to each network visualization discipline and by establishing and discussing a classification for the individual tasks. With this combined analysis of surveys and task taxonomies, we provide an overarching structure of the field, from which we extrapolate the current state of research and promising directions for future work.     

Silane-Mediated Expansion of Domains in Si-Doped κ-Ga2O3 Epitaxy and its Impact on the In-Plane Electronic Conduction

Unintentionally doped (001)-oriented orthorhombic κ-Ga₂O₃ epitaxial films on c-plane sapphire substrates are characterized by the presence of ≈ 10 nm wide columnar rotational domains that can severely inhibit in-plane electronic conduction. Comparing the in- and out-of-plane resistance on well-defined sample geometries, it is experimentally proved that the in-plane resistivity is at least ten times higher than the out-of-plane one. The introduction of silane during metal-organic vapor phase epitaxial growth not only allows for n-type Si extrinsic doping, but also results in the increase of more than one order of magnitude in the domain size (up to ≈ 300 nm) and mobility (highest µ ≈ 10 cm²V⁻¹s⁻¹, with corresponding lowest ρ ≈ 0.2 Ωcm). To qualitatively compare the mean domain dimension in κ-Ga₂O₃ epitaxial films, non-destructive experimental procedures are provided based on X-ray diffraction and Raman spectroscopy. The results of this study pave the way to significantly improved in-plane conduction in κ-Ga₂O₃ and its possible breakthrough in new generation electronics. The set of cross-linked experimental techniques and corresponding interpretation here proposed can apply to a wide range of material systems that suffer/benefit from domain-related functional properties.     

Reference architectures modelling and compliance checking

Software and Systems Modeling - Reference architectures (RAs) are successfully used to represent families of concrete software architectures in several domains such as automotive, banking, and the...     

Visual Exploration of Financial Data with Incremental Domain Knowledge

Modelling the dynamics of a growing financial environment is a complex task that requires domain knowledge, expertise and access to heterogeneous information types. Such information can stem from several sources at different scales, complicating the task of forming a holistic impression of the financial landscape, especially in terms of the economical relationships between firms. Bringing this scattered information into a common context is, therefore, an essential step in the process of obtaining meaningful insights about the state of an economy. In this paper, we present Sabrina 2.0, a Visual Analytics (VA) approach for exploring financial data across different scales, from individual firms up to nation-wide aggregate data. Our solution is coupled with a pipeline for the generation of firm-to-firm financial transaction networks, fusing information about individual firms with sector-to-sector transaction data and domain knowledge on macroscopic aspects of the economy. Each network can be created to have multiple instances to compare different scenarios. We collaborated with experts from finance and economy during the development of our VA solution, and evaluated our approach with seven domain experts across industry and academia through a qualitative insight-based evaluation. The analysis shows how Sabrina 2.0 enables the generation of insights, and how the incorporation of transaction models assists users in their exploration of a national economy.     

The ForeMoSt approach to building valid model-based safety arguments

Software and Systems Modeling - Safety assurance cases (ACs) are structured arguments designed to comprehensively show that a system is safe. ACs are often model-based, meaning that a model of the...