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Search Results (441)

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22 pages, 1109 KB  
Article
Drapeability and Λ-Frames
by Yevgenya Movshovich and John Wetzel
Geometry 2025, 2(4), 18; https://doi.org/10.3390/geometry2040018 - 4 Nov 2025
Viewed by 346
Abstract
In recent years, two quite different tools have been employed to study global properties of arcs in the plane. The first is drapeability, which grew from ideas of J. R. Alexander in early 2000s defining an arc drapeable if it lies in the [...] Read more.
In recent years, two quite different tools have been employed to study global properties of arcs in the plane. The first is drapeability, which grew from ideas of J. R. Alexander in early 2000s defining an arc drapeable if it lies in the convex hull of a shorter convex arc. The second is Λ-configuration, where an arc travels from one line to another and back. We investigate interrelations between these notions and in the process find drapeability criteria for open arcs, necessary and sufficient drapeability conditions for three-segment z-shaped arcs, and new bounds for the width of non-drapeable arcs. Full article
(This article belongs to the Special Issue Feature Papers in Geometry)
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25 pages, 1095 KB  
Article
Emotional Demands and Role Ambiguity Influence on Intentions to Quit: Does Trust in Management Matter?
by Ntseliseng Khumalo and Banji Rildwan Olaleye
Adm. Sci. 2025, 15(11), 424; https://doi.org/10.3390/admsci15110424 - 30 Oct 2025
Viewed by 1730
Abstract
Workers’ well-being is significantly influenced by the presence of clear and firm policies. This study examines the profound impact of members’ understanding of role ambiguity (ROA) on emotional demand and the pivotal role of trust in management in influencing turnover, as outlined in [...] Read more.
Workers’ well-being is significantly influenced by the presence of clear and firm policies. This study examines the profound impact of members’ understanding of role ambiguity (ROA) on emotional demand and the pivotal role of trust in management in influencing turnover, as outlined in the job demand-resources model. The study, which purposefully selected 290 public sector employees from Lesotho, utilized a structured research instrument and analyzed the results using partial least squares structural equational modeling (PLS-SEM). The findings, in line with the hypotheses, reveal that role ambiguity significantly contributes to both emotional demands and employees’ intentions to quit. Furthermore, the results demonstrate that emotional demands act as a mediator in the relationship between ROA and intention to quit. Trust in management also plays a moderating role in the relationship between role ambiguity and intention to quit, with a negligible effect on the link between ROA and emotional demand. This interaction between work-related demands and available resources deviates from the core principles of the JD-R model. The novel concept that trusts in management can influence employees’ plans to leave, even in the face of role ambiguity, was swiftly embraced by the public service sector and government ministry managers in Lesotho. This acceptance highlights the practical applicability of the JD-R model, which suggests that workers can effectively manage demanding and unfavorable aspects of work, such as job ambiguity, by having sufficient access to valuable resources. Full article
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8 pages, 301 KB  
Communication
Possible Reasons for the Suboptimal Response of the Cladribine Course in Daily Practice: An Independent Analysis of Data from 12 Russian Clinics and the Results of Post-Registration Studies in Other Countries
by Alexey N. Boyko, Valentina M. Alifirova, Daria V. Pashkovskaya, Ekaterina I. Kuchina, Stella A. Sivertseva, Elena L. Turova, Zoya A. Goncharova, Olga Yu Rudenko, Yulia Yu Pogrebnova, Farid A. Khabirov, Timur I. Khaibullin, Natalia N. Babicheva, Natalia L. Khoroshilova, Oksana V. Dzundza, Olga A. Soldatova, Anna N. Belova, Gennadyi E. Sheiko, Anastasia E. Makarova and Natalia G. Glavinskaya
Sclerosis 2025, 3(4), 34; https://doi.org/10.3390/sclerosis3040034 - 24 Oct 2025
Viewed by 439
Abstract
Objectives: The purpose of this study was to analyze the effect of daily intake of cladribine tablets on the course of multiple sclerosis (MS) while monitoring for 1–4 years during and after the course in several neurological clinics from different regions of the [...] Read more.
Objectives: The purpose of this study was to analyze the effect of daily intake of cladribine tablets on the course of multiple sclerosis (MS) while monitoring for 1–4 years during and after the course in several neurological clinics from different regions of the Russian Federation. Materials and Methods: Information was collected on 235 patients from 12 neurological clinics and regional centers for MS, who were observed for an average of 3.4 years after starting treatment with cladribine. Results: An independent analysis of cases of prescription of cladribine in tablets showed that the reason for prescription of cladribine was highly active MS (HAMS) in 159 patients (67.7%), rapidly progressive MS (RPMS) in 20 patients (8.5%), active remitting MS in 50 patients (21.3%) and secondary progressive MS (SPMS) with exacerbations in 6 (2.5%). Among them, only 12 patients (5.1%) had not previously received DMTs, i.e., in these cases, the drug was prescribed as the first DMT. In total, 22 patients had previously received natalizumab, 5—ocrelizumab, and in 1 case—fingolimod. The remaining 207 patients were crossed over from the first-line DMTs. In all cases, there was a decrease in the frequency of exacerbations during and after the completion of the course of cladribine. Exacerbations between the first and second courses of cladribine were noted in 36 patients (15.3% of all treated), almost half of the cases—those who previously received natalizumab (17 exacerbations, or 47.2% of all exacerbations between the 1st and 2nd courses of cladribine), and in 3 cases—from ocrelizumab (in 60% of all patients crossed over from ocrelizumab). During 4 years of follow-up after a full course of cladribine, exacerbations were in 14 patients (6% of all patients included in the analysis), of which in 6 cases—after crossover from natalizumab. Discussion and Conclusions: The data obtained are generally consistent with the results of meta-analyses and reviews published recently, but high probability of exacerbations in patients who were crossed over from second-line drugs such as natalizumab and ocrelizumab were seen. The crossover from natalizumab is carried out more often due to the increased risk of developing progressive multifocal encephalopathy (PML). It is likely that the restoration of MS activity after the withdrawal of natalizumab is quite frequent, cladribine tablets were not able to fully prevent this. Such a crossover does not seem to be optimal, unlike the crossover from first-line DMTs. If such a crossover is still planned, it could be performed within 4 weeks after stopping natalizumab. Full article
14 pages, 2515 KB  
Article
Assessment of Phytochemical Composition and Antifungal Activity of Micropropagated Drymis winteri Plants
by Julia Rubio, Christian Robles-Kelly, Evelyn Silva-Moreno, Héctor Carrasco and Andrés F. Olea
Plants 2025, 14(20), 3215; https://doi.org/10.3390/plants14203215 - 20 Oct 2025
Viewed by 596
Abstract
The search for sustainable alternatives to synthetic agrochemicals has fueled a growing interest in plant-derived bioactive compounds. Drimys winteri (canelo), a native Chilean tree of significant ethnobotanical importance, is a promising source of antifungal sesquiterpenes, such as polygodial and drimenol. This study describes [...] Read more.
The search for sustainable alternatives to synthetic agrochemicals has fueled a growing interest in plant-derived bioactive compounds. Drimys winteri (canelo), a native Chilean tree of significant ethnobotanical importance, is a promising source of antifungal sesquiterpenes, such as polygodial and drimenol. This study describes the development of an in vitro clonal micropropagation platform for D. winteri that enables the production of plant material under controlled laboratory conditions, which is subsequently submitted to extraction to obtain these bioactive compounds. Four tailored culture media have been formulated for successful propagation, rooting of plantlets, and callus induction. Histological analysis confirmed the presence of meristemoids in the dedifferentiated calli. Furthermore, HPLC and GC-MS analyses indicate that phytochemical composition of extracts of in vitro-propagated D. winteri and those from mature, wild-grown trees is quite similar. This result is in line with the antifungal activity against Botrytis cinerea exhibited by these extracts; namely, both are comparable. This biotechnological approach offers a scalable method for producing plant-based antifungal agents, contributing to sustainable agriculture and the valorization of native genetic resources. Full article
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26 pages, 2233 KB  
Article
Rheology for Wood Plastic Composite Extrusion—Part 1: Laboratory vs. On-Line Rheometry
by Krzysztof J. Wilczyński, Kamila Buziak, Adrian Lewandowski and Krzysztof Wilczyński
Polymers 2025, 17(20), 2782; https://doi.org/10.3390/polym17202782 - 17 Oct 2025
Viewed by 713
Abstract
Common polymeric materials (neat polymers) are quite well known, and their properties are often available in appropriate material databases. However, material data, e.g., rheological data, for materials such as polymer blends, polymer composites (including wood plastic composites), and filled plastics are simply lacking [...] Read more.
Common polymeric materials (neat polymers) are quite well known, and their properties are often available in appropriate material databases. However, material data, e.g., rheological data, for materials such as polymer blends, polymer composites (including wood plastic composites), and filled plastics are simply lacking in material databases. This paper addresses the problem of determining viscosity curves for one of the most widely used advanced polymeric materials: wood plastic composites. Studies were conducted in laboratory and production settings, i.e., on-line. Laboratory tests were conducted in two ways: on the basis of classical rheometric measurements, i.e., High-Pressure Capillary Rheometry (HPCR), and on the basis of Melt Flow Index (MFI) measurements, also including tests based on a limited number of measurement points. Tests in production conditions, i.e., on-line, were conducted during the extrusion process using the measurement of the process output (material flow rate) and pressure in a specialized extrusion die. The test results (viscosity curves) obtained from Melt Flow Index (MFI) measurements and on-line measurements were presented and evaluated against the background of the results (viscosity curves) obtained from classical capillary rheometry measurements (HPCR). Due to the lack of rheological data of wood plastic composites in available databases, in-house research methods based on the two-point viscosity curve determination in the plastometric (MFI) tests and the tests under production conditions, that is, on-line, have been proposed. The two-point method, based on the power law model, is quick and easy to implement, and allows for solving many polymer processing issues analytically. On-line tests have the significant advantage of being conducted under the actual flow conditions of the tested material, rather than under laboratory conditions, as is the case with rheometric and plastometric tests, which do not take into account the processing history of the tested material. The issues of rheology and modeling of wood plastic composite processing, e.g., extrusion and injection molding, which have not yet been resolved and require practical solutions, were also discussed. The results of this part of the study (viscosity curves and models) will be used in the second part of the study to evaluate the impact of rheological testing methods and rheological models on the accuracy of process modeling (extrusion). Full article
(This article belongs to the Special Issue Advances in Wood and Wood Polymer Composites)
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13 pages, 1413 KB  
Article
Evolution of Microplastics Released from Tea Bags into Water
by Alexander A. Yaroslavov, Anna A. Efimova, Tatyana E. Grokhovskaya, Anastasiia G. Badikova, Vasily V. Spiridonov, Denis V. Pozdyshev, Sergey V. Lyulin and Jose M. Kenny
Polymers 2025, 17(19), 2700; https://doi.org/10.3390/polym17192700 - 7 Oct 2025
Viewed by 3665
Abstract
Eight different types of tea bags were investigated in this work using dynamic light scattering, electrophoretic mobility and nanoparticle tracking analysis methods to determine the concentration and size of released particles from the bag materials at different temperatures and times. Infrared spectroscopy and [...] Read more.
Eight different types of tea bags were investigated in this work using dynamic light scattering, electrophoretic mobility and nanoparticle tracking analysis methods to determine the concentration and size of released particles from the bag materials at different temperatures and times. Infrared spectroscopy and calorimetric methods confirmed that the bag material consisted of synthetic (nylon or polypropylene) or natural polymers (cellulose). The size of the released particles lies in the range of 200 nm–1 µm with an initial bimodal distribution and with an average diameter of about 600 nm. The concentration of released particles increases with increasing temperature and brewing time. The released particles of synthetic polymers remain quite stable and are not affected by natural enzymes, while cellulose particles are easily degraded by the proteolytic complex Morikrase. When analyzing the electrophoretic mobility, it was found that the released particles have a negative surface charge, which probably determines the absence of cytotoxicity established on the epithelial cell line Caco-2 even at the maximum values of the observed particle concentrations (14 × 109 particle/L for synthetic polymers and 170 × 109 particle/L for cellulose). Full article
(This article belongs to the Special Issue Degradation and Stabilization of Polymer Materials 2nd Edition)
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24 pages, 495 KB  
Review
Dynamical Transitions in Trapped Superfluids Excited by Alternating Fields
by Vyacheslav I. Yukalov and Elizaveta P. Yukalova
Physics 2025, 7(3), 41; https://doi.org/10.3390/physics7030041 - 12 Sep 2025
Viewed by 729
Abstract
The paper presents a survey of some dynamical transitions in nonequilibrium trapped Bose-condensed systems subject to the action of alternating fields. Nonequilibrium states of trapped systems can be implemented in two ways: resonant and nonresonant. Under resonant excitation, several coherent modes are generated [...] Read more.
The paper presents a survey of some dynamical transitions in nonequilibrium trapped Bose-condensed systems subject to the action of alternating fields. Nonequilibrium states of trapped systems can be implemented in two ways: resonant and nonresonant. Under resonant excitation, several coherent modes are generated by external alternating fields with the frequencies been tuned to resonance with some transition frequencies of the trapped system. A Bose system of trapped atoms with Bose–Einstein condensate can display two types of the Josephson effect, the standard one, when the system is separated into two or more parts in different locations, or the internal Josephson effect, when there are no any separation barriers but the system becomes nonuniform due to the coexistence of several coherent modes interacting one with another. The mathematics in both these cases is similar. We focus on the internal Josephson effect. Systems with nonlinear coherent modes demonstrate rich dynamics, including Rabi oscillations, the Josephson effect, and chaotic motion. Under the Josephson effect, there exist dynamic transitions that are similar to phase transitions in equilibrium systems. The bosonic Josephson effect is shown to be implementable not only for quite weakly interacting systems, but also in superfluids with not necessarily as weak interactions. Sufficiently strong nonresonant excitation can generate several types of nonequilibrium states comprising vortex germs, vortex rings, vortex lines, vortex turbulence, droplet turbulence, and wave turbulence. Nonequilibrium states are shown to be characterized and distinguished by effective temperature, effective Fresnel number, and dynamic scaling laws. Full article
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18 pages, 17950 KB  
Article
From Structure to Function: The Impact of EGFR and IGF-IR in 3D Breast Cancer Spheroids
by Chrisavgi Gourdoupi, Spyros Kremmydas, Sylvia Mangani, Paraskevi Ioannou, Nikolaos A. Afratis, Zoi Piperigkou and Nikos K. Karamanos
Cancers 2025, 17(16), 2606; https://doi.org/10.3390/cancers17162606 - 8 Aug 2025
Cited by 2 | Viewed by 2079
Abstract
Background: Breast cancer, one of the most researched cancers in oncology, remains the primary cause of cancer-related mortality in women. Its biological complexity, which includes phenotypic, genetic, and microenvironmental aspects, makes modeling and treatment quite difficult. The need for more physiologically realistic [...] Read more.
Background: Breast cancer, one of the most researched cancers in oncology, remains the primary cause of cancer-related mortality in women. Its biological complexity, which includes phenotypic, genetic, and microenvironmental aspects, makes modeling and treatment quite difficult. The need for more physiologically realistic models is highlighted by the comparison of two-dimensional (2D) cell cultures with 3D breast-cancer-derived spheroids, which discloses how important pathways such as epidermal growth factor receptor (EGFR) and insulin-like growth factor I receptor (IGF-IR) influence cell behavior and extracellular matrix (ECM) macromolecular expression. Methods: The purpose of this study was to utilize novel 3D cell platforms to assess the effect of inhibiting the EGFR and IGF-IR pathways, alone or in combination, on the functional properties and the expression levels of certain matrix metalloproteinases (MMPs) which are implicated in breast cancer progression (i.e., triple-negative and luminal A breast cancer subtypes) and related with the EGFR and IGF-ΙR molecular network, as also demonstrated through STRING analysis. Results: Our results demonstrated potential crosstalk between EGFR and IGF-IR signaling, which influences cell proliferation and spheroid growth, dissemination, and migration. Significant phenotypic changes proposed between 2D and 3D cell cultures, and alterations in the expression of MMPs, were also recorded. Conclusions: Both breast cancer cell lines retained acknowledged characteristics across the tested models while also exhibiting new, condition-dependent properties. Overall, our findings enhance our understanding on the interplay between the EGFR and IGF-IR pathways and underscore the value of 3D models in revealing key biological processes underlying distinct breast cancer phenotypes. Full article
(This article belongs to the Special Issue Extracellular Matrix Proteins in Cancer)
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22 pages, 5335 KB  
Article
An Italian Study of PM0.5 Toxicity: In Vitro Investigation of Cytotoxicity, Oxidative Stress, Intercellular Communication, and Extracellular Matrix Metalloproteases
by Nathalie Steimberg, Giovanna Mazzoleni, Jennifer Boniotti, Milena Villarini, Massimo Moretti, Annalaura Carducci, Marco Verani, Tiziana Grassi, Francesca Serio, Sara Bonetta, Elisabetta Carraro, Alberto Bonetti, Silvia Bonizzoni, Umberto Gelatti and the MAPEC_LIFE Study Group
Int. J. Mol. Sci. 2025, 26(14), 6769; https://doi.org/10.3390/ijms26146769 - 15 Jul 2025
Viewed by 645
Abstract
Particulate matter (PM), mainly PM0.5, represents a significant concern for human health, particularly relating to lung homeostasis, and more research is required to ascertain its tissue tropism and the molecular pathways involved. In this study, we first focus on classical in [...] Read more.
Particulate matter (PM), mainly PM0.5, represents a significant concern for human health, particularly relating to lung homeostasis, and more research is required to ascertain its tissue tropism and the molecular pathways involved. In this study, we first focus on classical in vitro toxicological endpoints (cytotoxicity and cell growth) in human bronchial and alveolar epithelial cell lines mimicking the two pulmonary target tissues. Air samples were collected in five Italian cities (Brescia, Lecce, Perugia, Pisa, Turin) during winter and spring. To better decipher the PM0.5 effects on pulmonary cells, a further winter sampling was performed in Brescia, and studies were extended to assess tumour promotion, oxidative stress, and the activity of Matrix metalloproteases (MMP). The results confirmed that the effect of air pollution is linked to the seasons (winter is usually more cytotoxic than spring) and is correlated with the peculiar characteristics of the cities studied (meteoclimatic conditions, economic/anthropogenic activities). Alveolar cells were often less sensitive than bronchial cells. All PM samples from Brescia inhibited intercellular communication mediated by gap junctions (GJIC), increased the total content in glutathione, and decreased the reduced form of glutathione, whereas the Reactive Oxygen Species (ROS) content was almost constant. Long-term treatments at higher doses of PM decreased MMP2 and MMP9 activity. Taken together, the results confirmed that PM is cytotoxic and can potentially act as tumour promoters, but the mechanisms involved in oxidative stress and lung homeostasis are dose- and time-dependent and quite complex. Full article
(This article belongs to the Special Issue The Influence of Environmental Factors on Disease and Health Outcomes)
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51 pages, 669 KB  
Article
Negative Indefinite Constructions in Bantu: ‘Nobody’
by Maud Devos, Johan van der Auwera and Rasmus Bernander
Languages 2025, 10(6), 123; https://doi.org/10.3390/languages10060123 - 27 May 2025
Viewed by 3598
Abstract
This paper presents a first typology of negative indefinites in Bantu languages. The lack of interest in expressions of ‘nobody’ in Bantu languages is connected with the idea that they merely involve a generic noun for ‘person’ and main clause negation. Our study, [...] Read more.
This paper presents a first typology of negative indefinites in Bantu languages. The lack of interest in expressions of ‘nobody’ in Bantu languages is connected with the idea that they merely involve a generic noun for ‘person’ and main clause negation. Our study, based on a dataset of 85 Bantu languages, shows that exponents of ‘nobody’ can be quite diverse, either resembling exponents of ‘somebody’ or differing from them through the use of pragmatically strong modifiers like scalar additive operators or explicit quantifiers like the numeral ‘one’. We also look at the constructions in which exponents of ‘nobody’ occur and observe that next to canonical SVO constructions, two construction types are used which are known to express information structure in Bantu languages: inversion constructions and existential cleft constructions. Inversion constructions are shown to be especially frequent with intransitive clauses but we also find object inversion for either ‘somebody’ or ‘nobody’ but not for both in the same language. Existential cleft constructions, on the other hand, are shown to be especially frequent with transitive clauses and, more importantly, they are more frequently used for expressions of ‘nobody’ than for expressions of ‘somebody’ in line with recent observations for South-East Asian and Mixtec languages. Full article
(This article belongs to the Special Issue Recent Developments on the Diachrony and Typology of Bantu Languages)
21 pages, 15391 KB  
Article
Geochemical Study of Bitumen Residues on Potsherds from the al-Qusur Monastery (7th–9th c. CE): Composition and Origin
by Jacques Connan, Julie Bonnéric, Rémi Perrogon, Michael H. Engel, Renaud Gley, Alex Zumberge and Philippe Schaeffer
Molecules 2025, 30(9), 2006; https://doi.org/10.3390/molecules30092006 - 30 Apr 2025
Cited by 1 | Viewed by 837
Abstract
Geochemical and isotopic analysis of bitumen lining potsherds from the al-Qusur monastery (second half of the 7th c. CE and the middle of the 9th c. CE), at the central part of Failaka Island (Kuwait Bay), confirms the presence of two distinct compositional [...] Read more.
Geochemical and isotopic analysis of bitumen lining potsherds from the al-Qusur monastery (second half of the 7th c. CE and the middle of the 9th c. CE), at the central part of Failaka Island (Kuwait Bay), confirms the presence of two distinct compositional categories that can be matched to contemporary sources from two different areas of Iran: the Kermanshah province on one side, and the Khuzestan–Fars–Busher provinces on the other side. Potsherds comprise different types: TORP-S amphorae, TORP-C amphorae, SPORC storage jar, turquoise alkaline-glazed jar (TURQ.T), and CREAC jar. There is no relationship between the type of potsherd and the origin of bitumen. The bitumen coating SPORC jar, first identified as a kind of juice strainer to filter the «garum-like juice», was examined in greater details to try to identify traces of fish sauce mentioned in the Arabic kitchen books as ‘murri’, and quite similar to the Roman garum. The mineralogical analysis exhibits the classical minerals of archaeological mixtures (quartz, calcite, dolomite) and no halite. Hydrocarbons, alcohols, and methyl esters show a typical biodegraded bitumen signature but no fatty acids and terpenoids. It seems that the bitumen matrix has not adsorbed any molecules from the presumed «garum» filtered in the basin. Full article
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18 pages, 2436 KB  
Review
May the Extensive Farming System of Small Ruminants Be Smart?
by Rosanna Paolino, Adriana Di Trana, Adele Coppola, Emilio Sabia, Amelia Maria Riviezzi, Luca Vignozzi, Salvatore Claps, Pasquale Caparra, Corrado Pacelli and Ada Braghieri
Agriculture 2025, 15(9), 929; https://doi.org/10.3390/agriculture15090929 - 24 Apr 2025
Viewed by 1885
Abstract
Precision Livestock Farming (PLF) applies a complex of sensor technology, algorithms, and multiple tools for individual, real-time livestock monitoring. In intensive livestock systems, PLF is now quite widespread, allowing for the optimisation of management, thanks to the early recognition of diseases and the [...] Read more.
Precision Livestock Farming (PLF) applies a complex of sensor technology, algorithms, and multiple tools for individual, real-time livestock monitoring. In intensive livestock systems, PLF is now quite widespread, allowing for the optimisation of management, thanks to the early recognition of diseases and the possibility of monitoring animals’ feeding and reproductive behaviour, with an overall improvement of their welfare. Similarly, PLF systems represent an opportunity to improve the profitability and sustainability of extensive farming systems, including those of small ruminants, rationalising the use of pastures by avoiding overgrazing and controlling animals. Despite the livestock distribution in several parts of the world, the low profit and the relatively high cost of the devices cause delays in implementing PLF systems in small ruminants compared to those in dairy cows. Applying these tools to animals in extensive systems requires customisation compared to their use in intensive systems. In many cases, the unit prices of sensors for small ruminants are higher than those developed for large animals due to miniaturisation and higher production costs associated with lower production numbers. Sheep and goat farms are often in mountainous and remote areas with poor technological infrastructure and ineffective electricity, telephone, and internet services. Moreover, small ruminant farming is usually associated with advanced age in farmers, contributing to poor local initiatives and delays in PLF implementation. A targeted literature analysis was carried out to identify technologies already applied or at an advanced stage of development for the management of grazing animals, particularly sheep and goats, and their effects on nutrition, production, and animal welfare. The current technological developments include wearable, non-wearable, and network technologies. The review of the technologies involved and the main fields of application can help identify the most suitable systems for managing grazing sheep and goats and contribute to selecting more sustainable and efficient solutions in line with current environmental and welfare concerns. Full article
(This article belongs to the Section Farm Animal Production)
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30 pages, 20213 KB  
Article
hTERT and SV40LgT Renal Cell Lines Adjust Their Transcriptional Responses After Copy Number Changes from the Parent Proximal Tubule Cells
by Bruce Alex Merrick, Ashley M. Brooks, Julie F. Foley, Negin P. Martin, Rick D. Fannin, Wesley Gladwell and Kevin E. Gerrish
Int. J. Mol. Sci. 2025, 26(8), 3607; https://doi.org/10.3390/ijms26083607 - 11 Apr 2025
Viewed by 1120
Abstract
Primary mouse renal proximal tubule epithelial cells (moRPTECs) were immortalized by lentivirus transduction to create hTERT or SV40LgT (LgT) cell lines. Prior work showed a more pronounced injury and repair response in LgT versus hTERT cells after chemical challenge. We hypothesized that unique [...] Read more.
Primary mouse renal proximal tubule epithelial cells (moRPTECs) were immortalized by lentivirus transduction to create hTERT or SV40LgT (LgT) cell lines. Prior work showed a more pronounced injury and repair response in LgT versus hTERT cells after chemical challenge. We hypothesized that unique genomic changes occurred after immortalization, altering critical genes and pathways. RNA-seq profiling and whole-genome sequencing (WGS) of parent, hTERT, and LgT cells showed that 92.5% of the annotated transcripts were shared, suggesting a conserved proximal tubule expression pattern. However, the cell lines exhibited unique transcriptomic and genomic profiles different from the parent cells. Three transcript classes were quite relevant for chemical challenge response—Cyps, ion channels, and metabolic transporters—each important for renal function. A pathway analysis of the hTERT cells suggested alterations in intermediary and energy metabolism. LgT cells exhibited pathway activation in cell cycle and DNA repair that was consistent with replication stress. Genomic karyotyping by combining WGS and RNA-seq data showed increased gene copy numbers in chromosome 5 for LgT cells, while hTERT cells displayed gene copy losses in chromosomes 4 and 9. These data suggest that the exaggerated transcriptional responses of LgT cells versus hTERT cells result from differences in gene copy numbers, replication stress, and the unique selection processes underlying LgT or hTERT immortalization. Full article
(This article belongs to the Section Molecular Toxicology)
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27 pages, 2090 KB  
Review
Peptidergic Systems and Neuroblastoma
by Manuel Lisardo Sánchez and Rafael Coveñas
Int. J. Mol. Sci. 2025, 26(8), 3464; https://doi.org/10.3390/ijms26083464 - 8 Apr 2025
Viewed by 1467
Abstract
The peptidergic systems are involved in neuroblastoma. Peptides (angiotensin II, neuropeptide Y, neurotensin, substance P) act as oncogenic agents in neuroblastoma, whereas others (adrenomedullin, corticotropin-releasing factor, urocortin, orexin) exert anticancer effects against neuroblastoma. This plethora of peptidergic systems show the functional complexity of [...] Read more.
The peptidergic systems are involved in neuroblastoma. Peptides (angiotensin II, neuropeptide Y, neurotensin, substance P) act as oncogenic agents in neuroblastoma, whereas others (adrenomedullin, corticotropin-releasing factor, urocortin, orexin) exert anticancer effects against neuroblastoma. This plethora of peptidergic systems show the functional complexity of the mechanisms regulated by peptides in neuroblastoma. Peptide receptor antagonists act as antineuroblastoma agents since these compounds counteracted neuroblastoma cell growth and migration and the angiogenesis promoted by oncogenic peptides. Other therapeutic approaches (signaling pathway inhibitors, focal adhesion kinase inhibitors, peptide receptor knockdown, acetic acid analogs) that also counteract the beneficial effects mediated by the oncogenic peptides in neuroblastoma are discussed, and future research lines to be developed in neuroblastoma (interactions between oncogenic and anticancer peptides, combination therapy using peptide receptor antagonists and chemotherapy/radiotherapy) are also suggested. Although the data regarding the involvement of the peptidergic systems in neuroblastoma are, in many cases, fragmentary or very scarce for a particular peptidergic system, taken together, they are quite promising with respect to potentiating and developing this research line with the aim of developing new therapeutic strategies to treat neuroblastoma in the future. Peptidergic systems are potential and promising targets for the diagnosis and treatment of neuroblastoma. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Third Edition)
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22 pages, 4990 KB  
Article
Edge-Centric Embeddings of Digraphs: Properties and Stability Under Sparsification
by Ahmed Begga, Francisco Escolano Ruiz and Miguel Ángel Lozano
Entropy 2025, 27(3), 304; https://doi.org/10.3390/e27030304 - 14 Mar 2025
Viewed by 1305
Abstract
In this paper, we define and characterize the embedding of edges and higher-order entities in directed graphs (digraphs) and relate these embeddings to those of nodes. Our edge-centric approach consists of the following: (a) Embedding line digraphs (or their iterated versions); (b) Exploiting [...] Read more.
In this paper, we define and characterize the embedding of edges and higher-order entities in directed graphs (digraphs) and relate these embeddings to those of nodes. Our edge-centric approach consists of the following: (a) Embedding line digraphs (or their iterated versions); (b) Exploiting the rank properties of these embeddings to show that edge/path similarity can be posed as a linear combination of node similarities; (c) Solving scalability issues through digraph sparsification; (d) Evaluating the performance of these embeddings for classification and clustering. We commence by identifying the motive behind the need for edge-centric approaches. Then we proceed to introduce all the elements of the approach, and finally, we validate it. Our edge-centric embedding entails a top-down mining of links, instead of inferring them from the similarities of node embeddings. This analysis is key to discovering inter-subgraph links that hold the whole graph connected, i.e., central edges. Using directed graphs (digraphs) allows us to cluster edge-like hubs and authorities. In addition, since directed edges inherit their labels from destination (origin) nodes, their embedding provides a proxy representation for node classification and clustering as well. This representation is obtained by embedding the line digraph of the original one. The line digraph provides nice formal properties with respect to the original graph; in particular, it produces more entropic latent spaces. With these properties at hand, we can relate edge embeddings to node embeddings. The main contribution of this paper is to set and prove the linearity theorem, which poses each element of the transition matrix for an edge embedding as a linear combination of the elements of the transition matrix for the node embedding. As a result, the rank preservation property explains why embedding the line digraph and using the labels of the destination nodes provides better classification and clustering performances than embedding the nodes of the original graph. In other words, we do not only facilitate edge mining but enforce node classification and clustering. However, computing the line digraph is challenging, and a sparsification strategy is implemented for the sake of scalability. Our experimental results show that the line digraph representation of the sparsified input graph is quite stable as we increase the sparsification level, and also that it outperforms the original (node-centric) representation. For the sake of simplicity, our theorem relies on node2vec-like (factorization) embeddings. However, we also include several experiments showing how line digraphs may improve the performance of Graph Neural Networks (GNNs), also following the principle of maximum entropy. Full article
(This article belongs to the Section Information Theory, Probability and Statistics)
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