Expansion Conditions Research Articles

Организация обучения русскому языку как иностранному в школах Азии, Африки и Латинской Америки на основе российского учебно-методического онлайн-комплекса как стратегия экспорта образования

The aim of the research is to substantiate the high relevance of expanding pre-university Russian language education programs abroad to increase the level of Russian higher education export in terms of boosting demand among young people from Asia, Africa and Latin America. The paper examines the current picture of pre-university forms of Russian teaching abroad and determines the most effective form; investigates the existing conditions for the implementation of this form in Asia, Africa and Latin America and identifies the type of Russian methodological support necessary for its scaling. The scientific novelty of the research lies in defining one of the key conditions for the successful expansion of pre-university Russian language teaching programs abroad that consists in the organization of teaching the subject “Russian language” in foreign schools through the implementation of digital methodological support in the form of a Russian online training package to assist countries that do not have long-term experience in the implementation of Russian as a foreign language training programs. As a result of the research, the prospects of promoting the inclusion of the subject “Russian language” in the programs of foreign schools as a second foreign language in Asia, Africa and Latin America have been substantiated, as this form of education contributes to the effective organization of pre-university Russian language learning and the creation of positive ideas about the scientific and technological development of Russia among schoolchildren, forming their motivation and communication competencies for admission and successful study in Russian universities.

UM171 Enhances Fitness and Engraftment of Gene Modified Hematopoietic Stem Cells from Sickle Cells Disease Patients

Sickle cell disease (SCD) is one of the most common genetic blood diseases. Autologous hematopoietic stem cell gene therapy using lentiviral vectors is an effective therapeutic strategy for SCD. However, the occurrence of post gene therapy myelodysplastic syndrome and acute myeloid leukemia not related to vector insertion has suggested an underlying genetic risk or acquisition of damage during ex vivo culture or from proliferative stress associated with reconstitution. Here, we aimed to improve the transduction efficiency, stem cell fitness and reconstitution of SCD CD34+ cells transduced with a lentiviral vector (LV) containing BCL11A shmiR currently in clinical trials (Esrick et al. NEJM, 2021, NCT03282656), to minimize culture-induced stress and reduce genomic damage during ex vivo culture. UM171, an HSC self-renewal pyrimidoindole derivative agonist, has been shown to expand HSCs and enhance multilineage blood cell reconstitution in mice. We examined the effect of addition of UM171 during ex vivo transduction on HSCs from SCD patients. Culture of SCD CD34+ HSC in HSC expansion conditions with UM171 increased the proportion of CD34+CD133-CD45RA-CD90+ long term HSCs (LT-HSCs), from 1.1% to 4.1% (N = 3, P < 0.001), and the absolute number of LT-HSCs increased 4-fold (N = 3, P < 0.001). Treatment with UM171 also significantly enhanced the transduction efficiency of BCL11A shmiR containing lentiviral vector (LV-BCL11A) in SCD CD34+ cells from 0.7 vector copies/diploid genome (VCN) to 1.0 VCN (N = 5, P < 0.001), and significantly decreased apoptosis of stem cells from 22.5% to 14.3% (N = 3, P < 0.001), and DNA damage as measured by γ-H2AX from 10.6% to 6.6% (N = 3, P < 0.001). Given these results, we assessed the engraftment capability and clonality of SCD CD34+ transduced in the presence or absence of UM171 in NBSGW mice. UM171 increased the human CD45 engraftment of mice measured in BM at 16 weeks post-transplantation from 32.5% to 69.4% in hCD45+ BM cells (N = 6, P < 0.01) and enhanced the engraftment of transduced in SCD CD34+-derived CD45+ cells from 11.2% to 18.2% in gene-marked BM cells (N = 6, P < 0.01), while maintaining multilineage differentiation in this model. Barcode analysis revealed the engraftment of 500-1800 unique barcodes with a high degree of clonal diversity and a trend towards increased polyclonal engrafting populations in transplanted mice. To assess the effect of UM171 more rigorously on functionally defined HSCs, we performed a competitive transplantation assay using CD34+ cells transduced in the presence vs absence of UM171. Analysis of BM obtained from the mice at 16 weeks post-transplantation showed that cells transduced in the presence of UM171 consistently outcompeted those transduced under control conditions, 62.6% in gene-marked erythroid cells of UM171 treated cells compared with 37.4% of control cells (N = 9, P < 0.001), and UM171 maintains LV-BCL11A induced γ-globin expression in erythroid cells. In summary, a short-term exposure of SCD CD34+ PB cells to UM171 enhances stem cell fitness. Implementing these findings in clinical gene therapy protocols may improve the efficacy and sustainability of gene therapy and generate new opportunities in the field of gene editing.

A geographer's place matters: Reflections from a ‘local scholar’ and the politics of North/South knowledge production

AbstractThe most prominent and influential Geography literatures about the Global South are predominantly produced by scholars in the North and less so by intellectuals whose homes are located in the Global South—the ‘local scholars’. As a Cambodian scholar, I argue that the challenges of participating in collaborative, English language knowledge production derive not merely from skill disparities between international and ‘local’ academics, but also from constraints in finding the right platforms for research and academic expression. Constrained conditions for knowledge participation and expansion are rooted in a long history of colonialism in the Cambodian education system and the contemporary political economy of academia. Rather than directly engage with international intellectual and political discussions, in many cases, Cambodian scholars largely supply compelling stories—in the form of ethnographic evidence, data, images and affect to fuel theoretical debates taking place in the North. Beyond emphasising this well established inequity in the political economy of knowledge production, I contend that being ‘on the ground’ not only equips local scholars with contextual depths but also confines them to think and act locally.

PEDAGOGICAL CONDITIONS OF THE TRAINING OF ARTS FACULTY STUDENTS IN THE PROCESS OF STUDYING CONDUCTING AND CHORAL DISCIPLINES

The article examines the pedagogical conditions for the preparation of students of the faculties of arts for the formation of vocal-ensemble competence in the process of studying conducting and choral disciplines, namely: actualization of the motivation of students of the faculties of arts for constant creative growth; activation of dialogue interaction; systematic expansion of the music-pedagogical and creative-performance experience of future music teachers. The pedagogical condition of actualizing the motivation of art faculty students for constant creative growth is an important condition for the formation of vocal-ensemble competence of future music teachers, because motivation acts not only as a motivating force, but also is considered by us as a regulatory, controlling, evaluative, dynamic and procedural basis of musical performance activity. Pedagogical conditions for the activation of dialogic interaction in the process of music education are key, because the ability to establish constructive dialogues is one of the manifestations of the performing profession. At the same time, the process of mastering the profession is also built on interaction, on the formation of a dialogue between the teacher and the student. The third pedagogical condition for the systematic expansion of the musical-pedagogical and creative-performing experience of students of the faculties of arts extends to the theoretical knowledge of various concepts and approaches in education, which reflect various aspects of vocal and choral training.Keywords: students of arts faculties, pedagogical conditions, artistic education, conducting and choral disciplines, vocal and ensemble competence.

Conformations of borneol and isoborneol in the gas phase: Their monomers and microsolvation clusters.

Borneol is a natural monoterpene with significant applications in various industries, including medicine and perfumery. It presents several diastereomers with different physical and chemical properties, influenced by their unique structures and interactions with molecular receptors. However, a complete description of its inherent structure and solvent interactions remains elusive. Here, we report a detailed investigation of the gas-phase experimental structures of borneol and isoborneol, along with the description of their microsolvation complexes with the common solvents water and dimethyl sulfoxide. The molecules and complexes were studied using chirped-pulse Fourier transform microwave spectroscopy coupled to a supersonic expansion source. Although three rotamers are potentially populated under the conditions of the supersonic expansion, only one of them was observed for each monomer. The examination of the monohydrated complexes revealed structures stabilized by hydrogen bonds and non-covalent C-H⋯O interactions, with water as the hydrogen bond donor. Interestingly, in the clusters with dimethyl sulfoxide, borneol and isoborneol change their roles acting as donors. We further identified a higher-energy rotamer of the borneol monomer in one of the complexes with dimethyl sulfoxide, while that rotamer was missing in the experiment for the monomer. This observation is not common and highlights a specific position in borneol especially favorable for forming stable complexes, which could have implications in the understanding of the unique physical and chemical properties of the diastereomers.

Deflagration evolution of premixed H2/CH4/air mixture undergoing a sudden expansion near the ignition source in a half-open duct

Experiments were carried out in a half-open duct to investigate the deflagration evolution of premixed CH4/H2/air mixtures undergoing a sudden expansion. Obstacles were located over and under the ignition source to simulate a long and narrow flat gap, and when the flame shot through the gap into the main body of the explosion duct, it would undergo a process of sudden expansion. By adjusting the spacings (S) and widths (W) of the gap, a series of sudden expansion conditions were considered, and the flame propagation behaviors and explosion characteristics were investigated. The results showed that different extent of flame front inversion was observed under different size of gap conditions, including inclined flat flame, vertical flat flame and tulip flame. Besides, results indicated that the vortex pairs near the obstacles play an essential role in the flame front inversion phenomenon. In addition, it was also found that the maximum overpressure in the sudden expansion duct was much lower than that in the smooth duct or with obstacles in the middle of duct. In addition, the maximum pressure (Pmax) exhibits a concave function with the increase of W, and the minimum value of Pmax was obtained at W = 150 mm, S = 30 mm, which was closely related to the combined effect of venting and combustion expansion.

Near-Infrared-Responsive Rare Earth Nanoparticles for Optical Imaging and Wireless Phototherapy.

Near-infrared (NIR) light is well-suited for the optical imaging and wireless phototherapy of malignant diseases because of its deep tissue penetration, low autofluorescence, weak tissue scattering, and non-invasiveness. Rare earth nanoparticles (RENPs) are promising NIR-responsive materials, owing to their excellent physical and chemical properties. The 4f electron subshell of lanthanides, the main group of rare earth elements, has rich energy-level structures. This facilitates broad-spectrum light-to-light conversion and the conversion of light to other forms of energy, such as thermal and chemical energies. In addition, the abundant loadable and modifiable sites on the surface offer favorable conditions for the functional expansion of RENPs. In this review, the authors systematically discuss the main processes and mechanisms underlying the response of RENPs to NIR light and summarize recent advances in their applications in optical imaging, photothermal therapy, photodynamic therapy, photoimmunotherapy, optogenetics, and light-responsive drug release. Finally, the challenges and opportunities for the application of RENPs in optical imaging and wireless phototherapy under NIR activation are considered.

Human left ventricular cardiac fibroblasts undergo a dynamic shift in secretome and gene expression toward a cardiac myofibroblast phenotype during early passage in typical culture expansion conditions

Cardiac fibroblasts (CFs) are critical components of the cardiac niche and primarily responsible for assembly and maintenance of the cardiac extracellular matrix (ECM). CFs are increasingly of interest for tissue engineering and drug development applications, as they provide synergistic support to cardiomyocytes through direct cell-to-cell signaling and cell-to-ECM interactions via soluble factors, including cytokines, growth factors and extracellular vesicles. CFs can be activated to a cardiac myofibroblast (CMF) phenotype upon injury or stimulation with transforming growth factor beta 1. Once activated, CMFs assemble collagen-rich ECM, which is vitally important to stabilize scar formation following myocardial infarction, for example. Although there is greater experience with culture expansion of CFs among non-human strains, very little is known about human CF-to-CMF transitions and expression patterns during culture expansion. In this study, we evaluated for shifts in inflammatory and angiogenic expression profiles of human CFs in typical culture expansion conditions. Understanding shifts in cellular expression patterns during CF culture expansion is critically important to establish quality benchmarks and optimize large-scale manufacturing for future clinical applications.

ETHNO-CULTURAL COMPONENT DEVELOPMENT OF THE ACTIVITIES OF SPECIALISTS IN HUMANITARIAN SPECIALTIES IN THE PROCESS OF EDUCATIONAL PRACTICES

The authors investigate the development of the ethno-cultural component of the activities of specialists in humanitarian specialties in the process of educational practices. In modern conditions of multi-ethnic interaction in society, the acquisition of an ethno-cultural component in the process of educational practices is an important condition for training specialists in humanitarian specialties. In the conditions of war, when many teachers went abroad, and in the conditions of expansion of international cooperation, when foreign partners helped Ukraine to fight against the aggressor, ethno-cultural competence helped to establish new productive forms of partnership interaction and business relations. The ethno-cultural component of the activities of a humanitarian specialist with people of other nationalities contributes to a better understanding of their cultural needs and the development of the ability to interact and cooperate with them. It is important for a humanitarian teacher not only to master the language, culture, worldview, and psychological characteristics of other peoples, not only to adopt other people's experiences but also to spread his own based on his own Ukrainian identity. The formation of the ethno-cultural component of activity will allow specialists in humanitarian specialties to reveal the peculiarities of the worldview, behavior, and activities of representatives of other peoples determined by their traditional culture. The ethno-cultural component of the activities of a specialist in humanitarian specialties will enable him to effectively influence and prevent negative manifestations of the ethnic culture of young people. The ethno-cultural component of the activities of humanitarian specialists is a crucial component of professional activities with foreign partners and migrants.
 The article proves that the development of the ethno-cultural component of the activity of specialists in humanitarian specialties in the process of educational practices is a necessary element of their further professional activity. It is significant to develop practical skills related to the psychology of different ethnic groups, ethnic cultures, and religions of the world, intercultural communication, national consciousness, ethnic tolerance, identity, and national state-building during the educational practices of specialists in humanitarian specialties. 
 To ensure the high-quality training of specialists in humanitarian specialties and their acquisition of the necessary ethno-cultural component in their future activities, the authors suggest the introduction of various educational practices, as well as the educational disciplines «Modern Regional Cultural Practice» and «Folk Artistic Culture» into the educational programs of training specialists in humanitarian specialties.
 The possibilities of technologies for the organization of ethno-cultural practice are considered (in particular: ethnographic expeditions to the places of compact residence of various ethnic groups and the collection of ethnographic material; independent work on the planning of ethno-cultural work in educational and cultural institutions; preparation of reports at mini-conferences; conducting research and ethnographic work; scientific circle) and practical technologies of ethno-cultural activity (in particular: participation of future specialists in humanitarian specialties in folklore groups; involvement in scientific activities, participation in contests and defenses of scientific works; familiarization with methods of recording folklore, regional household traditions, rituals; participation in ethno collectives and folklore ensembles; involvement to ethno-evenings and folklore events; independent research and ethnographic activities; researching the peculiarities of Ukrainian embroidery in one’s region; recording legends and beliefs about work; gathering a collection of ancient household and household items; studying little-known labor customs and rites of a particular ethnic group; systematization of folk humorous creativity, etc.).

Production of massive W±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$W^{\\pm }$$\\end{document} bosons and fermion–antifermion pairs from vacuum in the de Sitter Universe

In this paper we study the charged electro-weak interactions in the de Sitter geometry. We develop the reduction formalism for the Proca field with the help of the solutions for the interacting fields. Perturbation theory is used for obtaining the definition of the transition amplitudes in the first order. We apply our formalism to the study of spontaneous vacuum emission of fermions, anti-fermions and W±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$W^{\\pm }$$\\end{document} bosons in the expanding de Sitter universe. Our results are generalizations of the Weinberg–Salam electro-weak theory to curved space-time, in the case of W±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$W^{\\pm }$$\\end{document} boson interaction with leptons. The probability and transition amplitude are found to be a quantities which depend on the Hubble parameter. Our analytical and graphical results prove that such perturbative processes are possible only for the large expansion conditions of the early Universe. The total probability and rate of transition are obtained for the case of large expansion and we use dimensional regularization for the momenta integrals. In the end we recover the Minkowski limit, where our probabilities vanish, thus confirming the well known fact that spontaneous vacuum emission of W±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$W^{\\pm }$$\\end{document} bosons and fermions is forbidden in flat space-time due to energy–momentum conservation.

Comprehensive evaluation of urban development suitability based on constraints and development factors: A case study of the central urban area of Zhengzhou, China

The overcapacity and overdevelopment of cities have led to various environmental hazards and resource depletion, making it crucial to evaluate the suitability of urban development. This research field provides scientific evidence and policy recommendations to improve land use quality and distribution. However, contemporary studies solely focus on construction land versus non-construction land competition, ignoring potential constraints from agriculture and ecology on parcel development. Using the land use situation of Zhengzhou City, this study comprehensively evaluated urban development suitability through hierarchical analysis, Delphi method, and eight-direction analysis. A multi-attribute overlay was applied with spatial restrictions from ecological protection and agricultural production, combined with urban expansion and development conditions. The results indicated that: (1) Ecological protection was critical for sustainable urban development, and areas like the Yellow River coast, northwest wetland, and southwest woodland were significant for ecological protection. High suitability areas for agricultural production were primarily located within the existing cultivated land. (2) Regarding urban expansion, the southeast of the city center was identified as the most suitable area, mainly covered by dryland. (3) Overall, the unsuitable, basically unsuitable, medium, suitable, and highly suitable areas for urban development covered 244, 921, 3024, 2224, and 944 km2, respectively. (4) The southeast-northwest direction showed prominent spatial characteristics for urban development suitability, while intensive development mode dominated the east-west direction of the city center. These findings provide significant guidance for land development and utilization, optimizing the spatial pattern, and formulating policies in Zhengzhou. Nevertheless, the weight calculation process presents a subjective factor that needs to be addressed in future research. More objective weight calculation results are necessary to achieve a more scientifically rigorous evaluation of urban development suitability.

Using systems thinking to understand the scale-up and sustainability of health innovation: a case study of seasonal malaria chemoprevention processes in Burkina Faso

BackgroundScale-up and sustainability are often studied separately, with few studies examining the interdependencies between these two processes and the implementation contexts of innovations towards malaria prevention and control. Researchers and implementers offer much more attention to the content of innovations, as they focus on the technological dimensions and the conditions for expansion. Researchers have often considered innovation a linear sequence in which scaling up and sustainability represented the last stages. Using systems thinking in this manuscript, we analyze complex scaling and sustainability processes through adopting and implementing seasonal malaria chemoprevention (SMC) in Burkina Faso from 2014 to 2018.MethodsWe conducted a qualitative case study involving 141 retrospective secondary data (administrative, press, scientific, tools and registries, and verbatim) spanning from 2012 to 2018. We complemented these data with primary data collected between February and March 2018 in the form of 15 personal semi-structured interviews with SMC stakeholders and non-participant observations. Processual analysis permitted us to conceptualize scale-up and sustainability processes over time according to different vertical and horizontal levels of analysis and their interconnections.ResultsOur results indicated six internal and external determinants of SMC that may negatively or positively influence its scale-up and sustainability. These determinants are effectiveness, monitoring and evaluation systems, resources (financial, material, and human), leadership and governance, adaptation to the local context, and other external elements. Our results revealed that donors and implementing actors prioritized financial resources over other determinants. In contrast, our study clearly showed that the sustainability of the innovation, as well as its scaling up, depends significantly on the consideration of the interconnectedness of the determinants. Each determinant can concurrently constitute an opportunity and a challenge for the success of the innovation.ConclusionOur findings highlight the usefulness of the systemic perspective to consider all contexts (international, national, subnational, and local) to achieve large-scale improvements in the quality, equity, and effectiveness of global health interventions. Thus, complex and systems thinking have made it possible to observe emergent and dynamic innovation behaviors and the dynamics particular to sustainability and scaling up processes.

FEATURES OF THE WORK ORGANIZATION OF INSURANCE COMPANIES OF UKRAINE DURING THE PERIOD OF ARMED INVASION

The article is devoted to the definition of the main aspects of the organization of work of insurance companies of Ukraine during the period of armed invasion. The purpose of the article is to determine the effects on the work of insurance companies in the modern conditions of the armed invasion of Russian aggressors and to provide proposals regarding the priority areas of insurance management. The object of the research is the processes of organization and management of the work of insurance companies. The subject of the study is the ways of optimizing the work of insurers in conditions of external and internal negative influences. The research used general scientific and special research methods: comparative analysis, scientific abstraction and generalization of the scientific experience of modern theoretical studies, a system-complex approach. When conducting an analysis of the dynamics of the number of insurance organizations and gross insurance payments and premiums for the period 2017-2022, it was found that fluctuations in their volumes also occurred in pre-war times. The main reasons that made it possible to effectively reduce the number of insurance service providers without a significant loss of the client base, while simultaneously increasing the guarantee requirements for insurers, were identified. It has been proven that even in the pre-war period, conditions were created for strengthening requirements for corporate governance, introducing a civilized procedure for withdrawing insolvent insurers from the market, and implementing Solvency II. It is noted that Russia's sudden insidious attack caused a wave of violations and disruptions in the work of almost all domestic business entities. revealed that during 2022, the activities of insurance companies and other participants of the financial market of Ukraine took place in the conditions of the maximum limit of destabilization, and the volume of services fell significantly compared to the pre-war period. The structure of assets and liabilities of life insurers and risk insurers in 2022 was studied, and the largest insurance premiums and payments by region of Ukraine as of January 1, 2023 were identified.According to the results of the research conducted by Mrthe development and further development within the framework of state programs and on a unified conceptual basis of the methodology of managing insurance companies in conditions of war, the creation and expansion of a modern intellectual knowledge base of this subject area are recognized as priority areas of insurance management. It was emphasized that measures to ensure the organization of the work of insurance companies during the armed invasion should be based on advanced management techniques using the latest technologies.

Cytokines impact natural killer cell phenotype and functionality against glioblastoma in vitro.

Natural killer (NK) cells are a part of the innate immune system and first-line defense against cancer. Since they possess natural mechanisms to recognize and kill tumor cells, NK cells are considered as a potential option for an off-the-shelf allogeneic cell-based immunotherapy. Here, our objective was to identify the optimal cytokine-based, feeder-free, activation and expansion protocol for cytotoxic NK cells against glioblastoma in vitro. NK cells were enriched from human peripheral blood and expanded for 16 days with different activation and cytokine combinations. The expansion conditions were evaluated based on NK cell viability, functionality, expansion rate and purity. The cytotoxicity and degranulation of the expanded NK cells were measured in vitro from co‑cultures with the glioma cell lines U‑87 MG, U‑87 MG EGFR vIII, LN-229, U-118 and DK-MG. The best expansion protocols were selected from ultimately 39 different conditions: three magnetic cell‑selection steps (Depletion of CD3+ cells, enrichment of CD56+ cells, and depletion of CD3+ cells followed by enrichment of CD56+ cells); four activation protocols (continuous, pre-activation, re-activation, and boost); and four cytokine combinations (IL-2/15, IL‑21/15, IL‑27/18/15 and IL-12/18/15). The expansion rates varied between 2-50-fold, depending on the donor and the expansion conditions. The best expansion rate and purity were gained with sequential selection (Depletion of CD3+ cells and enrichment of CD56+ cells) from the starting material and pre-activation with IL‑12/18/15 cytokines, which are known to produce cytokine-induced memory-like NK cells. The cytotoxicity of these memory-like NK cells was enhanced with re-activation, diminishing the donor variation. The most cytotoxic NK cells were produced when cells were boosted at the end of the expansion with IL-12/18/15 or IL-21/15. According to our findings the ex vivo proliferation capacity and functionality of NK cells is affected by multiple factors, such as the donor, composition of starting material, cytokine combination and the activation protocol. The cytokines modified the NK cells' phenotype and functionality, which was evident in their reactivity against the glioma cell lines. To our knowledge, this is the first comprehensive comparative study performed to thisextent, and these findings could be used for upscaling clinical NK cellmanufacturing.

Comparability exercise of critical quality attributes of clinical-grade human mesenchymal stromal cells from the Wharton’s jelly: single-use stirred tank bioreactors versus planar culture systems

Background aimsThe increasing demand of clinical-grade mesenchymal stromal cells (MSCs) for use in advanced therapy medicinal products (ATMPs) require a re-evaluation of manufacturing strategies, ensuring scalability from two-dimensional (2D) surfaces to volumetric (3D) productivities. Herein we describe the design and validation of a Good Manufacturing Practice–compliant 3D culture methodology using microcarriers and 3-L single-use stirred tank bioreactors (STRs) for the expansion of Wharton's jelly (WJ)-derived MSCs in accordance to current regulatory and quality requirements. MethodsMSC,WJ were successfully expanded in 3D and final product characterization was in conformity with Critical Quality Attributes and product specifications previously established for 2D expansion conditions. ResultsAfter 6 days of culture, cell yields in the final product from the 3D cultures (mean 9.48 × 108 ± 1.07 × 107 cells) were slightly lower but comparable with those obtained from 2D surfaces (mean 9.73 × 108 ± 2.36 × 108 cells) after 8 days. In all analyzed batches, viability was >90%. Immunophenotype of MSC,WJ was highly positive for CD90 and CD73 markers and lacked of expression of CD31, CD45 and HLA-DR. Compared with 2D expansions, CD105 was detected at lower levels in 3D cultures due to the harvesting procedure from microcarriers involving trypsin at high concentration, and this had no impact on multipotency. Cells presented normal karyotype and strong immunomodulatory potential in vitro. Sterility, Mycoplasma, endotoxin and adventitious virus were negative in both batches produced. ConclusionsIn summary, we demonstrated the establishment of a feasible and reproducible 3D bioprocess using single-use STR for clinical-grade MSC,WJ production and provide evidence supporting comparability of 3D versus 2D production strategies. This comparability exercise evaluates the direct implementation of using single-use STR for the scale-up production of MSC,WJ and, by extension, other cell types intended for allogeneic therapies.

Expansion free spherical anisotropic solutions

We investigate the behavior of expansion free collapsing fluids, as studied by L. Herrera, A. Di Prisco and J. Ospino [Symmetry 15 (2023) 754], in the framework of [Formula: see text] gravity, which represents a modification of Einstein’s general relativity by establishing a function of the Ricci scalar [Formula: see text] in the gravitational action. We explore dynamical equations from Bianchi identities that demonstrate the motion and evolution of physical systems under the influence of gravitational fields. We match the inner and outer geometries of spacetime on the hypersurface to develop junction conditions by using the Misner–Sharp formalism. This allows us to identify the connection between mass functions for the inner and outer space as well as the relationship for heat flux [Formula: see text] and radial pressure [Formula: see text]. We also investigate analytical solutions of dissipative fluid distribution that fulfill the vanishing expansion condition together with the vanishing complexity factor constraint. For this, we introduce new constraints that permit the integration of the complex system in [Formula: see text] gravity. Next, we extract a set of differential equations that explain the dynamical structure of the dissipative spheres both in geodesic and non-geodesic fluids. Furthermore, we explore the physical characteristics of the obtained solutions, such as heat flux, energy density, shear stress, fluid’s temperature along with tangential and radial pressure, to assess their viability in describing real astrophysical systems.

Bionomics and population dynamics of anopheline larvae from an area dominated by fish farming tanks in northern Brazilian Amazon.

In Brazilian Amazon, deforestation and other anthropogenic activities as a consequence of human occupation have created new and artificial larval habitats for anopheline mosquitoes, providing conditions for oviposition, development and expansion of malaria vector populations. This study aimed to structurally characterize and describe the entomological and limnological parameters of Anopheles larval habitats from a malaria region in northern Brazilian Amazon. Fifty-two larval habitats were investigated in the District of Ilha de Santana, in the Brazilian state of Amapá, comprising fish farming tanks, ponds, and streams. For entomological parameters, the immature larvae were collected monthly from July 2019 to June 2020. For limnological parameters, the water samples were collected from 20 larval habitats during the sampling period. The data were analyzed using Generalized Linear Models, Multivariate analyses, and Kruskal-Wallis tests. Fifty habitats were positive for Anopheles larvae and a total of nine species were collected. The fish farming tanks had the highest abundance of larvae compared with ponds and streams. Anopheles darlingi, Anopheles nuneztovari s.l. and Anopheles triannulatus were collected in 94% of the larval habitats and showed the highest positivity index. The degree of shade and the type of water of the breeding sites were important factors for the presence of the main malaria vector, A. darlingi. This species was the most affected by pH, total dissolved solids, electrical conductivity, and nitrate. Our findings indicate that fish farming tanks are major contributors to vector anopheline abundance and malaria transmission. Vector control strategies focused on these habitats are urgently needed.

Predicted vs Observed Valve to Coronary Distance in Valve-in-Valve TAVR: A Computed Tomography Study

BackgroundPreprocedural computed tomography (CT) workup with assessment of virtual transcatheter heart valve-to-coronary ostia (VTC) distance and transcatheter heart valve-to-sinus (VTS) distances is recommended to assess the risk of coronary obstruction following valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR). ObjectivesThe authors sought to investigate the agreement of predicted VTC and VTS distances and observed post-TAVR anatomy on CT and their relationship with transcatheter heart valve (THV) expansion and deployment conditions. MethodsFifty-one patients who underwent a balloon-expandable ViV procedure were included in this study. The expansion of the THV stent frame was evaluated at 4 levels: THV inflow, surgical heart valve (SHV) sewing ring, SHV outflow, and THV outflow. Assessment of the VTC/VTS distances was performed on the pre-TAVR CT, and THV-to-coronary ostia and THV-to-sinus distances were assessed on the post-TAVR CT. ResultsFollowing the ViV procedure, the THV stent frame flared toward the outflow but was generally underexpanded at all levels, particularly at the SHV sewing ring level. Postdilatation impacted the extent of THV expansion, resulting in greater expansion than nominal balloon filling at all 4 THV levels (P < 0.001). Observed THV-to-coronary ostia distances were systematically larger than predicted by the VTC distance (mean difference 1.25 ±1.28 mm) in patients with nominal balloon filling but systematically smaller in case of postdilatation (mean difference −0.45 ± 0.52 mm). A similar relationship was observed between VTS and THV-to-sinus distance measurements. ConclusionsWith nominal balloon filling, VTC and VTS distances underestimate postprocedural distances due to THV frame underexpansion. However, postdilatation may lead to distances smaller than predicted due to THV overexpansion at the outflow level.

The cosmological evolution condition of the Planck constant in the varying speed of light models through adiabatic expansion

There have been various varying speed of light (VSL) models with one free parameter, b, to characterize the time variation of the speed of light as a function of a scale factor, c=c0ab/4, based on the expanding universe. One needs to induce cosmological evolutions of other physical constants and quantities having different powers of scale factor as a function of b to satisfy all known local physics laws, including special relativity, thermodynamics, and electromagnetic force. These models should be based on the Friedmann–Lemaître–Robertson–Walker metric satisfying the isotropic and homogeneous three-space known as the cosmological principle. Adiabaticity is a necessary condition to keep homogeneity and isotropy because a net energy flux would falsify the isotropy if there is a preferential energy flow direction. It also might forge homogeneity if the outward (inward) flow is isotropic. Thus, any VSL model based on the expanding universe should preserve an adiabatic expansion condition to be a viable model. We show that this condition specifies the cosmological evolution of the Planck constant as ħ=ħ0a−b/4.

Morphoelastic modelling of pattern development in the petal epidermal cell cuticle.

We use the model system Hibiscus trionum as a vehicle to study the origin and propagation of surface nano-ridges in plant petal epidermal cells by tracking the development of the cell shape and the cuticle. In this system, the cuticle develops two distinct sub-layers, (i) an uppermost layer which increases in thickness and in-plane extension and (ii) a substrate, composed of cuticular and cell wall material. We quantify the pattern formation and geometrical changes and then postulate a mechanical model assuming that the cuticle behaves as a growing bi-layer. The model is a quasi-static morphoelastic system and it is numerically investigated in two- and three-dimensional settings, using different laws of film and substrate expansion and boundary conditions. We recreate several features of the observed developmental trajectories in petals. We establish the respective roles of the layers' stiffness mismatch, the underlying cell-wall curvature, the cell in-plane expansion and the thickness growth rates of the layers in determining the observed pattern features, such as the variance observed in the amplitude and wavelength of the cuticular striations. Our observations provide evidence which justifies the growing bi-layer description, and provide valuable insights into why some systems develop surface patterns and others do not.