Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4⁺CD25⁺Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the level of ROS gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis; When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality was significantly decreased.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n=232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n=37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether in-dependence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and eth-nicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

Superconducting YBa2Cu3Oy (YBCO) foams were prepared using commercial open-cell, polyurethane foams as starting material to form ceramic Y2BaCuO5 (Y-211) foams which are then converted into superconducting YBCO by using the infiltration growth process. For modelling the superconducting and mechanical properties of the foam samples, a Kelvin-type cell may be employed as a first approach like done in the literature for pure polyurethane foams. However, for a refined model of a superconducting foam sample, the real sample structure must be considered. Thus, a proper description of the specific microstructure of the superconducting YBCO foams is required. A variety of parameters including the cell size and shape, the window size and shape, the length and shape of the foam struts or ligaments and the respective angles of intersection are used to describe the real foam structure. To obtain a set of reliable data, YBCO foam samples were investigated using optical microscopy, SEM and electron backscatter diffraction (EBSD). The detailed investigation of the foam microstructure reveals not only the differences to the polymeric foams used as base material, but also gives insight to details of the infiltration growth process via the increased surface amount in a foam sample.

In recent times, a great interest has been motivated in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, lupane-type triterpenes are phytochemicals that exert significant activities against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose‐limiting toxic effects and chemoresistance. Herein, we investigated the structure-activity relationship of six pentacyclic triterpenes: oleanolic acid (OleA), ursolic acid (UrA), asiatic acid (AsA), betulinic acid (BeA), betulin (Betu), lupeol (Lupe), on NSCLC A549 cells. From our studies, we confirmed that all these triterpenes showed cytotoxicity in the mid µM range, where BeA showed the strongest effect. Then, we determined that most of these triterpenes induced S-phase and G2/M phase cycle arrest, reactive oxygen species, mitochondrial depolarization, and caspase 3 activation. For chemoresistance markers, we elucidated that most triterpenes downregulated STAT3 and PDL1 genes. In contrast, ursane-type UrA and AsA also induced DNA damage, reactive nitrogen species and autophagy. These results showed that even slight structural changes in these triterpenes can influence the cellular response and mechanistic pathways. This study opens promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

Melt mixing is a convenient method to prepare polymer nanocomposites, but the extent of the dispersion of the solid filler reached is often limited, and may compromise the anticipated performance of these materials during service. Since the efficiency of extensional flows on dispersion is now well recognized, several mixers were designed with the aim of inducing both shear and extensional flow components. This work combines experimental and numerical data to better understand the kinetics of the dispersion of graphite nanoplates in a polypropylene melt, using a mixing device that consists of a series of stacked rings with equal outer diameter and alternating larger and smaller inner diameters, thus creating a series of converging/diverging flows. Numerical simulation of the flow using the opensource OpenFOAM software assuming both inelastic and viscoelastic responses predicted the velocity, streamlines, flow type and shear and normal stress fields for the mixer. Experimental and computed data were combined to determine the trade-off between the local degree of dispersion of the PP/GnP nanocomposite, measured as Area ratio, and the absolute average value of the hydrodynamic stresses multiplied by the local cumulative residence time. From considerations based on a theoretical approach to dispersion, the cohesive strength of the GnP agglomerates studied was estimated to be in the range 3 - 10kPa.

Idiopathic lung fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates in a reactive manner all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by Lysotracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial Lysotracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s which behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expresses AEC2s and basal cell markers resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of Lysotracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5 and CD24 expression in human lung epithelial cells. Combining functional analysis with extra- and intra- cellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole cell to acellular pertussis vaccines, although other factors may also contribute. To develop future vaccines and improve current vaccination strategies, it is critical to understand factors influencing the generation of immunological memory. We applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. These findings were correlated to vaccine-specific plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days post-vaccination was the most prominent cellular change in all age groups, and was most pronounced for more mature IgG1+ plasma cells. Cellular responses were stronger in individuals primed with whole cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ plasma cell expansion weakly correlated with Prn- and PT- specific serum IgG levels. Our study points at plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and priming backgrounds.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

Physical properties like shape, volume and size affect the dynamics of biological systems. Along these lines, we focus on the topological properties of biological fluids and their biochemical and physiological outcomes. We take as a paradigmatic example the salivary fluid and describe how its topological features may affect the physiopathology of the oral cavity. Topological approaches assess the general properties of saliva, ignoring small-scale physical details such as density, flow rate, stiffness, viscosity. Specifically, the mucin aggregates scattered in the salivary fluid can be tackled in terms of topological holes, i.e., vortical clusters that modify the direction, flow, impulse, local rate-of-change and velocity of saliva. While the current methodological approaches are inclined to remove the effects of impurities assessing systems as homogeneous structures, we argue that the occurrence of mucins breaks up the salivary fluid’s homogeneity, leading to unexpected biophysical modifications. We suggest that every collected salivary sample is not reliable for accurate clinical and experimental investigation, since it displays highly local as well as variable chemical, physical and biological features, not reflecting the current physiological state of the oral cavity. Therefore, the assessment of a single salivary sample is not fully reproducible and cannot provide information about the biophysical, enzymatic and microbiological content of the whole saliva. In sum, the very topological features of the saliva - such as volume, shape, antipodal cells, vortex area, whirling fluid mass, segmentation, discretization, triangulation, node numbering - produce unnoticed biological consequences and network connectivity features with intriguing operational implications.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.

Pressure drop and flow pattern of oil-water flows were investigated in a 19 mm ID clear polyvinyl chloride pipe consisting of U-bend with radius of curvature of 100 mm. The range for oil and water superficial velocities tested were and respectively. Measurements were carried out under different flow conditions in a test section that consisted of four different parts: upstream of the bend, at the bend and at two redeveloping flow locations after the bend. The result indicated that the bend had limited influence on downstream flow patterns. However, the shear forces imposed by the bend caused some shift flow pattern transition and bubble characteristics in the redeveloping flow section after the bend relative to develop flow before the bend. Generally, pressure gradient at all the test sections increased with both oil fraction and water superficial velocity and there was a sharp change of pressure gradient profile during phase inversion. The transition point where phase inversion occurred was always within the range of . Pressure losses differed at the various test sections and the difference was strongly linked to the superficial velocity of the phases and the flow pattern. At high mixture velocity, pressure losses at the redeveloping section after the bend were higher than that at the bend and that for fully developed flows. At low mixture velocity, pressure losses at the bend are higher than in the straight sections. Pressure drop generally decreased with level of flow development downstream of the bend.

Although Mast cells are known as key drivers of type I allergic reactions, there is increasing evidence for their critical role in host defense. MCs do not only play an important role in initiating innate immune responses, but also influence the onset, kinetic and amplitude of the adaptive arm of immunity, or fine-tune the mode of the adaptive reaction. Intriguingly, MCs have been shown to affect T cell activation by direct interaction or indirectly by modifying properties of antigen-presenting cells, and can even modulate lymph node-borne adaptive responses remotely from the periphery. In this review, we provide a summary of recent findings that explain how MCs act as a link between the innate and the adaptive immunity, all the way from sensing inflammatory insult to orchestrating the final outcome of the immune response.

In this study we discuss critical issues in modelling the structure and function of lymph nodes (LNs), with emphasis on how LN physiology is related to its multi-scale structural organization. In addition to macroscopic domains such as B-cell follicles and the T cell zone, there are vascular networks which play a key role in the delivery of information to the inner parts of the LN, i.e., the conduit and blood microvascular networks. We propose object-oriented computational algorithms to model the 3D geometry of the fibroblastic reticular cell (FRC) network and the microvasculature. Assuming that a conduit cylinder is densely packed with collagen fibers, the computational flow study predicted that the diffusion should be a dominating process in mass transport than convective flow. The geometry models are used to analyze the lymph flow properties through the conduit network in unperturbed- and damaged states of the LN. The analysis predicts that elimination of up to 60–90 % of edges is required to stop the lymph flux. This result suggests a high degree of functional robustness of the network.

The evolution of photovoltaic cells is intrinsically linked to advancements in the materials from which they are fabricated. This review paper provides an in-depth analysis of the latest developments in silicon-based, organic, and perovskite solar cells, which are at the forefront of photovoltaic research. We scrutinize the unique characteristics, advantages, and limitations of each material class, emphasizing their contributions to efficiency, stability, and commercial viability. Silicon-based cells are explored for their enduring relevance and recent innovations in crystalline structures. Organic photovoltaic cells are examined for their flexibility and potential for low-cost production, while perovskites are highlighted for their remarkable efficiency gains and ease of fabrication. The paper also addresses the challenges of material stability, scalability, and environmental impact, offering a balanced perspective on the current state and future potential of these material technologies.

The flow properties of pellets or granules are crucial for further processing the drug dosage forms. Optimal compression or filling the multiparticulate dosage forms into capsules is influenced by forces between discrete particles, which could be partially characterized by flow properties. Several techniques were developed for the examination of flowability, including static and dynamic methods applying empirical studies and the up-to-date chaos theory; however newest methods seem only to be powerful with the supplement of empirical principles. Our experiments try to refine both the technique of analysis and the methods by finding new, alternative ways. Our approach to the flowability measurements was to set up a dynamic time-dependent model which combines empirical observations and the chaos theory on a geometrical basis, thus find new aspects regarding flow properties of pellets and granules that could be relevant for drug developers.

This study will present a comprehensive review of the two-phase flow boiling heat transfer coefficient of hydrocarbons such propane (R-290), butane (R-600) and iso-butane (R-600a) and ethanol at various experimental conditions. Studying the multiphase flow heat transfer coefficient has a crucial importance for many heat transfer equipment to achieve higher efficiency for more compact design and cost reduction. One reason behind choosing hydrocarbons as refrigerants in this study is because hydrocarbons have zero ozone depletion potential (ODP=0) and insignificant direct global warming potential (GWP = 3). Moreover, thermodynamic and thermophysical characteristics of hydrocarbons qualify them to be a strong candidate for more heat transfer applications. Initially, by constructing a database for the working fluids from various experimental work available in the literature. The current data that this study has collected for the flow boiling of spans wide ranges of parameters, such as: mass flux, heat flux, operating pressure, and saturation temperature, etc. Furthermore, by comparing the experimental multiphase heat transfer coefficient database with the anticipated values of each correlation, the prediction performance of 26 correlations found in the literature was assessed. This study leads to the selection of the best prediction method based on the minimum deviation of predicted results from the experimental database provided by calculated mean absolute error (MAE) from the assessed correlations. The findings of this study can also be useful in the development of more accurate correlation methods for these fluids and improve the prediction of their flow boiling characteristics.

Optical micro-angiography (OMAG) is a new method of detecting flow rate and widely used for in vivo imaging. Although OMAG can distinguish between flowing and stationary parts, it cannot obtain accurate flow rate information. This study proposed a range formula for OMAG and the ultrahigh-sensitivity OMAG (UHS-OMAG) method to quantify the measurement range of an entire system. The parameters of the angle between beam scanning and flow directions, the angular velocity of the galvanometer, and the offset of incident light were introduced, and a formula for calculating the range was derived. Experiments were conducted to measure fine and ultra-fine flow rates by using OMAG and UHS-OMAG methods. The minimum measured flow rate was approximately 30 μm/s, and the maximum measured flow rate was approximately 8 mm/s. Experimental results are in good agreement with the preset results.

Mechanical ventilation systems, which are used for breathing support when a person is not able to do it by their own, requires a device for measuring the air flow to the patient in order to monitoring and a assure the magnitude establish by a medical staff. Flow sensors are the conventional devices used for the air flow measuring; however, there were not available in Peru, because of the international demand during COVID-19 pandemic. In this sense, a novel air flow sensor based on orifice plate and an intelligent transducer stage were developed as an integrated design. Advanced methodologies in simulations and experiments using specially designed equipment for this application were carried out. The obtained data was used for a mathematical characterization and dimensions validation of the integrated design. The device was tested in its real working conditions, it was implemented in a breathing circuit connected to a low-cost mechanical ventilation system based on cams. Results indicate that the designed air flow sensor/transducer is a low-cost complete medical device for mechanical ventilators able to provide satisfactorily all the ventilation parameters air flow, pressure and volume over time by measuring the air flow and calculating the others. Furthermore, this device provides directly a filtered equivalent electrical signal for a display or a computer.

Epigenetic modifications play a significant role in determining the fate of AFSC in terms of differentiation into multiple lineages. There is a tight correlation among DNA methylation, histone modifications, and small noncoding RNAs during the epigenetic control of stem cells differentiation. The present study investigates the role of miRNAs in differentiation of AFSC and addresses how their unique signatures contribute to lineage-specific differentiation. miRNAs profile was assessed in AFSC after 4 weeks of endothelial and muscular differentiation. Our results showed a decreased expression of for 5 miRNAs (miR-125b-5p, hsa-miR-18a-5p, hsa-miR-137, hsa-miR-21-5p and hsa-let-7a-5p) and an increased expression for 12 miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, hsa-let-7e-5p) in EPC compared with undifferentiated AFSC. Smooth muscle differentiation of AFSC revealed significant changes in 9 miRNAs from total of 84 tested; 3 were downregulated (miR-18a-5p, miR-137, sa-miR-21-5p) and 6 were upregulated (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, hsa-miR-375). miRNAs are molecular regulators of cell fate and differentiation, recent advances in molecular biology techniques revealed miRNA regulatory networks that can provide us information of endothelial and muscle cell biology in terms of homeostasis, growth, differentiation, and vascular function.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

The dynamic and never exactly repeatable tumor transcriptomic profile of people affected by the same form of cancer requires a personalized and time-sensitive approach of the gene therapy. The Gene Master Regulators (GMRs) were defined as genes whose highly controlled expression by the homeostatic mechanisms commands the cell phenotype by modulating major functional pathways through expression correlation with their genes. The Gene Commanding Height (GCH), a measure that combines the expression control and expression correlation with all other genes, is used to establish the gene hierarchy in each cell phenotype. We developed the experimental protocol, the mathematical algorithm and the computer software to identify the GMRs from transcriptomic data in surgically removed tumors, biopsies or blood from cancer patients. The GMR approach is illustrated with applications to our microarray data on human kidney, thyroid and prostate cancer samples, and on thyroid, prostate and blood cancer cell lines. We proved experimentally that each patient has his/her own GMRs, that cancer nuclei and surrounding normal tissue are governed by different GMRs, and that manipulating the expression has larger consequences for genes with higher GCH. Therefore, we launch the hypothesis that silencing the GMR may selectively kill the cancer cells from a tissue.

Imaging flow cytometry (ImFC) represents a significant technological advancement in the field of cytometry, effectively merging the high-throughput capabilities of flow analysis with the image-based features of microscopy. In this comprehensive review article, we take a historical perspective and delve into the evolution of this methodology, presenting its past, exploring current state-of-the-art and forecasting potential future advancements. The inception of ImFC arose from the innovative combination of a flow cytometer's hydraulics with the technology of an advanced camera. This synergistic coupling facilitated the morphological analysis of cell populations at a high-throughput scale, effectively evolving the landscape of cytometry. However, the application of ImFC faced several challenges. Among the most prominent ones, is the development and implementation of software systems that can reliably and efficiently handle the robust data acquisition and analysis inherent in ImFC. The scale and complexity of the data generated by ImFC necessitates the creation of novel analytical tools that can effectively manage and interpret this data, thus allowing us to unlock the full potential of ImFC. Interestingly, artificial intelligence (AI) algorithms have begun to be implemented on ImFC, offering a promise for enhancing analytical capabilities. The adaptability and learning capacity of AI may prove to be essential in knowledge mining from high-dimensional data produced by ImFC, potentially enabling more accurate analyses. Looking forward, we project that ImFC may become an indispensable tool, not only in research laboratories but also in clinical settings. Given the unique combination of high-throughput cytometry and detailed imaging offered by ImFC, we foresee a critical role for this technology in the next generation of scientific research and diagnostics. As such, we encourage both current and future scientists to consider the integration of ImFC as an addition to their research toolkit and clinical diagnostic routine.

Objectives: The purposes of this study were to 1) analyze the disruption of intracardiac flow by flow components and kinetic energy (KE) parameters in single ventricle physiology patients and compare with controls; 2) investigate left ventricular diastolic dysfunction in terms of 4D flow parameters in repaired Fontan (rFontan) group; 3) compare intracardiac flow parameters in morphologic LV and RV rFontan patient groups. Methods: Twenty-five rFontan patients (age: 10±3, M/F: 15/10) and fourteen controls (age: 10±2, M/F: 8/6) were prospectively recruited. All underwent cine and 4D flow cardiovascular magnetic resonance (CMR) on 3.0T scanner. Cardiac function and inter-ventricular mechanical dyssynchrony were analyzed using cine images. From 4D flow CMR, ventricular flow components were assessed: direct flow, retained inflow, delayed ejection flow and residual volume. Global and regional blood flow KE parameters, normalized to end-diastolic volume (EDV) were analyzed for functional single ventricle (FSV). Left ventricular (LV) diastolic dysfunction was assessed on echocardiography guidelines. Results: In comparison of rFontan vs. controls, median FSV residual volume (28% vs. 23%, P= 0.034) were higher in rFontan; median FSV direct flow (32% vs. 40%, P=0.005) and delayed ejection flow (17% vs. 24%, P=0.024) were lower in rFontan. FSV KEiEDV parameters were all lower in rFontan (all P<0.05). No significant differences were observed for flow components and KE parameters between patients with and without inter-ventricular dyssynchrony. FSV direct flow (AUC=0.76, Sensitivity=86%, Specificity=70%) was an independent predictor of LV diastolic dysfunction. Residual volume and E-wave KEiEDV were significantly different between morphologic RV and morphologic LV patient group. Conclusions: The changed flow pattern and decreased KE may be hemodynamic disturbances and impaired ventricular filling in rFontan patients. Reduced direct flow is associated with LV diastolic dysfunction. Morphologic right ventricular subgroup is worse than morphologic left ventricular group in terms of the intracardiac hemodynamics.

This study focuses on traffic condition analysis, especially in under developing country India and makes more visible of traffic flow by using traffic flow theory in order to understand real traffic condition. India is one of rapid economic growing countries and large market with second largest population 1.3 billion in 2018. On the other hand, there are social issues such as environment air pollution and global warming by traffic CO2 emission of transportation. This kind of condition is not only in India, but in other South East Asia and Africa in future. From recent more than one-month traffic observation in a typical major city Ahmedabad in Gujarat state, which has about 8 million population and industrialized city. In terms of traffic data collection, 14 CCTV cameras are used in the city. Based on multiple traffic cameras monitoring, author found the unique traffic flow characteristics and compares traffic flow theory. In this study, it is described what is key parameters to show real traffic congestion condition and how these congestion occurs.

The aim of this study is to model hydrodynamic processes of the Istanbul Strait with its stratified flow characteristic and calibrate the most important parameters using local and global search algorithms. For that two open boundary conditions are defined, which are in the North and South part of the Strait. Observed bathymetric, hydrographic, meteorological and water level data are used to set up the Delft3D-FLOW model. First, the sensitivities of model parameters on the numerical model outputs are assessed using PEST toolbox. Then, the model is calibrated based on the objective functions focusing on the flowrates of upper and lower layers. The salinity and temperature profiles of the Strait are only used for model validation. The results show that the calibrated model outputs of Istanbul Strait are reliable and consistent with the in-situ measurements. The sensitivity analysis reveals that the Spatial Low-Pass Filter Coefficient, Horizontal Eddy Viscosity, Prandtl-Schmidt Number, Slope in log-log Spectrum and Manning Roughness Coefficient are most sensitive parameters affecting flowrate performance of the model. The agreement between observed salinity profiles and simulated model outputs is promising whereas the match between observed and simulated temperature profiles is weak showing that the model can be improved particularly for simulating the mixing layer.

Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of proliferation and carcinogenesis evolution. FZD proteins, a family of receptors comprised in the Wnt signaling pathway, play an important role in carcinogenesis of gastroenteric tract. Here, a still unrecognized role of Frizzled 10 (FZD10) protein was identified. In particular, the presence of FZD10 and FZD10-mRNA in exosomes extracted from culture medium of the untreated colorectal, gastric, hepatic and cholangio cancer cell lines, was detected. A substantial reduction in the FZD10 and FZD10-mRNA level was achieved in FZD10-mRNA silenced cells and in their corresponding exosomes and, concomitantly a significant decrease in viability of the silenced cells compared to their respective controls was observed. Interestingly, the incubation of silenced cells with exosomes extracted from culture medium of the same untreated cells promoted a remarkable restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization

Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autolo-gous cell lines. Being among the most commonly used large domesticated hoofed animals and serving as a vital source of food and bioreactors, cattle are among the many species in which PSCs have been developed. Bovine PSCs (bPSCs) are the "seed cells" of regenerative science and have immense potential to advance species propagation, genetic engineering, and disease treatment. Moreover, they can aid in screening new drugs for efficacy and toxicity, model human diseases, and establish a sustainable agricultural system that can cater to the needs of the growing global population. Establishing stable bPSCs in vitro has been a critical scientific challenge, and researchers have made numerous attempts to address this issue. This review primarily delves into the current research progress of bPSCs, the challenges faced, and their potential applications.

In the last two decades many detailed full transcriptomic studies on complex biological samples have been published and included in large gene expression repositories. These studies primarily provide bulk expression signal for each sample, including multiple cell-types mixed within the global signal. The cellular heterogeneity in these mixtures does not allow the activity of specific genes in specific cell types to be identified. Therefore, inferring relative cellular composition is a very powerful tool to achieve a more accurate molecular profiling of complex biological samples. In recent decades, computational techniques have been developed to solve this problem by applying cell deconvolution methods, designed to decompose cell mixtures into their cellular components and calculate the relative proportions of these elements. Some of them, only calculate the cell proportions (supervised methods), while other deconvolution algorithms can also identify the gene signatures specific for each cell type (unsupervised methods). In these work, five deconvolution methods (CIBERSORT, FARDEEP, DECONICA, LINSEED and ABIS) were implemented and used to analyze blood and immune cells, and also cancer cells, in complex mixture samples (using three bulk expression datasets). Our study provides three analytical tools (corrplots, cell-signature plots and bar-mixture plots) that allow a thorough comparative analysis of the cell mixture data. The work indicates that CIBERSORT is a robust method optimized for the identification of immune cell-types, but not as efficient in the identification of cancer cells. We also observed that LINSEED is a very powerful unsupervised method that provides precise and specific gene signatures for each of the five main immune cell-types analyzed: neutrophils and monocytes (in the myeloid lineage), B-cells, NK cells and T-cells (in the lymphoid lineage).

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

Hospital bed shortage is a worldwide concern. Beds unavailability has caused elective surgery cancellations, at our hospital peaking in spring 2016 at over 50%. This is often due to difficult patient step-down from intensive care (ICU) and high-dependency units (HDU). In our general/digestive surgery service admitting approximately 1000 patients yearly, ward rounds were run on a consultant firm basis. We report a quality improvement (ISRCTN13976096) introducing in our service a structured daily multi-disciplinary board round framework (SAFER Surgery R2G) adapted from the “SAFER patient flow bundle” and the "Red to Green days” approaches to enhance flow, comparing the previous year to 2017, when our framework was applied for 12 months.We used a Plan-Do-Study-Act (PDSA) methodology. Our intervention consisted in 1) systematic communication of the key care plan after the afternoon ward rounds to the nurse in charge; 2) 30’ 10AM Monday-to-Friday multidisciplinary board rounds, attended daily by the senior-team and weekly by hospital and site managers, revising the key care plan aiming at safe, early discharges, assessing the appropriateness of each inpatient day and tackling any cause of delay. We measured patient flow by average length of stay (LOS), ICU/HDU step-downs and operation cancellations count, monitoring safety through early 30-day readmissions. Compliance was assessed by board round attendance and staff satisfaction rate surveys.After 12 months (PDSA 2, N=1032), LOS significantly decreased from 7.2(±8.9) to 6.3(±7.4) days (p=0.003); ICU/HDU bed step-down flow increased by 9.3% from 345 to 375 (p=0.197), surgery cancellations dropped from 38 to 15 (p=0.100). 30-day re-admissions increased from 0.9% (N=9) to 1.3% (N=14)(p=0.390). Average cross-specialty attendance was 80%. Satisfaction rates were >75%, regarding enhanced teamwork and faster decisions.The SAFER Surgery R2G framework has shown an increase in patient flow in the context of an enhanced multidisciplinary approach, requiring senior staff commitment to remain sustainable.

Background: Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether sex of the newborn affects the lymphocyte subpopulations in cord blood. Methods: 9 B and 21 T cell subpopulations were characterized by flow cytometry in human cord blood from 16 male and 21 female newborns, respectively. Results: Except for marginal zone B cells and transitional B cells, B cell count in all subsets was higher in cord blood of male newborns than in female newborns. Frequency of naive thymus negative Th cells was significantly higher in male cord blood whereas the remaining T cell subpopulations showed a higher count in cord blood of female newborns. Conclusion: Our study is the first revealing sex differences in B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system urging the need to expand research in this area.

Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 7 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. We focused on articles hypothesizing the identification and study of compounds that induce proliferation and osteogenic differentiation of the two d-DSC populations, representing an interesting issue for regenerative medicine. The reconstruction of bone defects in fact is still a challenge for personalized medicine.

This study aimed to enhance a micro hydroelectric generator system driven by free-flow vortex and to compare efficiency of Propeller and Crossflow turbines. Series of turbines in each type were designed and tested at water-flowrate of 0.02 m3/s. The turbine housing has 1 meter in diameter and 0.5-meter height with 2 meters outlet drain at the bottom. The best efficiency extracted from Crossflow turbines with the same height (0.3 meter) but different in diameter (0.4, 0.5, 0.6, and 0.7 meter) and numbers of blade (12, 18, 24, 30, and 23) was from an 18 blades turbine at 23.01% of efficiency. The best efficiency extracted from Propeller turbines with 5 blades was from a 0.4-meter-high turbine with a diameter of 0.7 meter at 13.92% of efficiency. There were 12 Propeller turbines designed in this study. They were different in height (0.2, 0.3, and 0.4 meter) and, in each height, 0.4, 0.5, 0.6, and 0.7 of diameter was applied. The result revealed that Cross Flow turbine had more efficiency to the system than Propeller turbine (9.09%) at the water-flowrate of 0.02 m3/s

Design criteria for coastal defenses exposed to wave overtopping are usually assessed by mean overtopping discharges and maximum individual overtopping volumes. However, it is often difficult to give clear and precise limits of tolerable overtopping for all kind of layouts. A few studies analyzed the relationship between wave overtopping flows and hazard levels for people on sea dikes, confirming that one single value of admissible mean discharge or individual overtopping volume is not a sufficient indicator of the hazard, but detailed characterization of flow velocities and depths is required. This work presents the results of an experimental campaign aiming at characterizing the flow characteristics associated to maximum individual overtopping volumes for an urbanized stretch of a town along the Catalan coast, where a walking and bike path and a railway run along the coastline are exposed to significant overtopping events every stormy season. The work compares different safety criteria for pedestrian. Results prove that safety of pedestrian on a sea dike can be still guaranteed even for overtopping volumes larger than 1000 l/m. Pedestrian hazard is rather proved to be linked to the combination of overtopping flow velocity and flow depth.

The paper presents a modeling framework to analyze the effect of episodic rainfall supply on groundwater dynamics in the Ionian coastal plain multilayered aquifer. The focus is essentially on the short-term behavior of the shallowest layer, with a specific analysis on episodic rainfall events. In the studied aquifer, groundwater level responds sensitively to rainfall events, highlighting the presence of preferential recharge zones. The hydraulic head peak is a function of groundwater level antecedent to the rainfall event. A kinematic dispersion wave model was used to model infiltration processes via preferential pathways. A one-dimensional and non-linear particle based numerical model was developed. Particles with constant water volume travel according to celerity and hydraulic dispersion to simulate the infiltration rate wave through the vadose zone. The flow rate that reaches the water table represents the input function to determine groundwater level fluctuations along groundwater flow direction and according to the lithological features of the surficial levels of the multilayered aquifer, its storage capacity changes passing from unconfined to confined conditions. The model was validated with high time resolution time series of precipitation and groundwater level coming from Terra Montonata meteo-climatic and groundwater level monitoring station. The developed model represents a basis for evaluating and predicting groundwater discharge of the shallowest layers of the Ionian coastal multilayered aquifer under natural conditions including episodic rainfall.

Photovoltaic is one of the promising renewable sources of power to meet the future challenge of energy need. Organic and perovskite thin film solar cells are an emerging cost-effective photovoltaic technology because of low-cost manufacturing processing and a light-weight. The main barrier of commercial use of organic and perovskite solar cells is the poor stability of devices. Encapsulation of these photovoltaic devices is one of the best ways to address this stability issue and enhance the device lifetime by employing materials and structures that possess high barrier performance for oxygen and moisture. The aim of this review paper is to find different encapsulation materials and techniques for perovskite and organic solar cells according to the present understanding of reliability issues. It discusses the available encapsulate materials and their utility in limiting chemicals such as water vapour, oxygen penetration. It also covers the mechanisms of mechanical degradation within the individual layers and solar cell as a whole, and possible obstacles to their application in both organic and perovskite solar cells. The contemporary understanding of these degradation mechanisms, their interplay and their initiating factors (both internal and external) are also discussed.

Heart attacks and strokes are one of the leading causes of death in the world today, and heart attacks caused by clogged arteries that carry blood to the heart muscle are a significant part of these strokes. These are caused by the accumulation of fat particles in the walls of the arteries and the reduction of blood flow through it over a long process. The process of fat penetration in the underlying layers of the Artery wall has been the focus of many researchers, and various researches and Simulations have been done on it, in each of them, the effect of specific parameters has been considered. In the present study, the effect of blood flow rate on the flow pattern in a bifurcate artery with two ducts has been investigated using FLUENT software with Computation fluid dynamic Method. The effect of the angle between the two ducts of the Artery on the flow pattern has been investigated.

Environmental darkness signal is transferred from the retina to the pineal gland triggering melatonin secretion. Melatonin influences the synthesis and release of the hypothalamic GnRH and the adenohypophyseal gonadotropin hormones and therefore, regulates testicular function in photoperiodic species. Besides the brain, direct actions of melatonin at the testicular level have also been described. Melatonin released from the pineal gland to the circulation is taken up by peripheral tissues including testes. Testicular synthesis of melatonin has also been reported. The two key somatic cell types in the testis, Leydig and Sertoli cells, express melatonergic receptors. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences the oxidation state and the energy metabolism, and consequently may regulate spermatogenesis. Melatonergic receptors were also described in testicular macrophages and mast cells of infertile patients. Whereas melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, it provides protective effects against oxidative stress in testicular mast cells. These data pinpoints melatonin as a key player in the regulation of testicular physiology (i.e. steroidogenesis, spermatogenesis) mostly in seasonal breeders. More importantly, melatonin is also involved in the modulation of testicular inflammatory and oxidant/anti-oxidant states in patients with idiopathic infertility.

Multicellular organisms organize themselves according to two principles; first, the equilibrium between the driving force of unstable state cells and apoptosis or senescence; and second, the mutual equilibrium between the functional requirements of different types of cells. For the first principle, we deduce that stem cells at different levels have their own growth limits, which are determined by two factors: the ability of the stem cells to enter an unstable state (specifically, the ability of cells to divide and differentiate); and the rate of cellular senescence, loss of function, and finally, apoptosis. The superposition of stem cell limits at different levels over each other can amplify small differences at the genetic level. Moreover, the growth limits of different organs are different, which lead to different individuals having completely different appearances. The second principle is that the sum of the specific output functions of an organ must be equal to the overall demand for the function to be provided by the organ. If negative entropy input can meet this equilibrium, defects in certain genes will cause these defective individuals to become larger or develop other morphology.

Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in case of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly underinvestigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes do not influence the respective other cell types’ migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels in the presence of supporting cells, whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe for the first time increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance to elucidate the molecular mechanisms of SC-LEC interaction.

Debris flows have generated major disasters worldwide due to their great destructive capacity, which is associated with their high energy levels and short response times. To achieve an adequate risk management of these events, it is necessary to define as accurately as possible the different hazard levels to which the territory is exposed. This article develops a new methodology to estimate this hazard based on the hydrodynamic characteristics of the flow and the granulometry of the sediments that can be mobilized by the flow. The hydrodynamic characteristics of the flow are determined through a mathematical modeling that considers the rheology of non-Newtonian flows and the different volumes of sediments that could be transported during events corresponding to different return periods. The proposed methodology was implemented in the Jamundí River basin (Colombia). The results obtained indicate that in the upper part of this basin there is a low hazard level, while in the lower part of the basin approximately 15% of the affected territory has a medium hazard level and the remaining 85% has a low hazard level. The methodology developed is simple to implement but technically rigorous since it considers all relevant aspects in the generation of debris flows.

The two-phase flow of water and reactive gas in the channel of proton exchange membrane fuel cell (PEMFC) plays an important role in high-quality water management. In this study, the removal effect of 3D wave channel and 2D straight channel for liquid water was studied by volume of fluid method. The dynamic behavior of droplet emerge from the gas diffusion layer (GDL) into the channel under the influence of gas flow was investigated. The effects of droplet growth, deformation, detachment, force, pore size on water critical behavior and water content in the channel are discussed. The results show that the 3D wave channel is superior to the removal of liquid water than the 2D straight channel. The increase of velocity is conducive to the discharge liquid water. While infinite increase of velocity will cause more parasitic power loss. The larger pore size of GDL is not advantageous to the performance of PEMFC, but the appropriate increase of pore size is conducive to the discharge of liquid water. The basic knowledge obtained in this study will help to deepen the understanding of droplet dynamics in PEMFC gas channels, and help to optimize the design and working conditions of these channels.

Dams design and their operation cause strong environmental alteration and therefore a long-term debate is ongoing for the scale of these projects. At the same time, the concept of Environmental Flow Assessment (EFA) is a crucial element of modified ecosystems featuring large infrastructure such as dams and reservoirs for mitigating potential environmental degradation while they operate. Nowadays, integrated scientific frameworks are required to quantify the risks caused by large infrastructure. Through the use of stochastic analysis, it is possible to quantify these uncertainties, and present a solution that incorporates long-term persistence and environmental sustainability into a balanced reservoir simulation model. In this work, an attempt is made to determine a benchmark reservoir size incorporating hydrological and ecological criteria though stochastic analysis. The primary goal is to ensure the best possible conditions for the ecosystem, and then secondarily to allow a steady supply of water for other uses. Using a synthetic timeseries based on historical inputs, it is possible to determine and preserve essential statistical characteristics of a river’s streamflow, and use these to detect the optimal reservoir capacity that maximizes environmental and local water demand reliability.

Unsteady flow is the most common and complicated form of fluid motion in nature. This paper takes the beaches of key waterways in the middle and lower reaches of the Yangtze River as the research object, analyzes the water surface distribution and average flow velocity distribution near the beach, and analyzes the differences. The relationship between the flow pattern of the steep slope and the water flow pattern of the entire survey area and the steep slope of the beach and its nearby water flow structure. The water flow near the beach is divided into four major blocks: the swelling water area, the falling water area, the backwater area and the maximum flow rate area. The water flow structure characteristics and the cause of each block are analyzed.

Widely used in hydraulics, the Colebrook equation for flow friction relates implicitly to the input parameters; the Reynolds number, Re and the relative roughness of inner pipe surface, ε/D with the output unknown parameter; the flow friction factor, λ; λ=f(λ, Re, ε/D). In this paper, a few explicit approximations to the Colebrook equation; λ≈f(Re, ε/D), are generated using the ability of artificial intelligence to make inner patterns to connect input and output parameters in explicit way not knowing their nature or the physical law that connects them, but only knowing raw numbers, {Re, ε/D}→{λ}. The fact that the used genetic programming tool does not know the structure of the Colebrook equation which is based on computationally expensive logarithmic law, is used to obtain better structure of the approximations which is less demanding for calculation but also enough accurate. All generated approximations are with low computational cost because they contain a limited number of logarithmic forms used although for normalization of input parameters or for acceleration, but they are also sufficiently accurate. The relative error regarding the friction factor λ, in best case is up to 0.13% with only two logarithmic forms used. As the second logarithm can be accurately approximated by the Padé approximation, practically the same error is obtained also using only one logarithm.

The oscillating heat pipe (OHP) is a new member in the family of heat pipes, and it has great potential applications in energy conservation. However, the fluid flow and heat transfer in the OHP as well as the fundamental effects of inner diameter on them have not been fully understood, which are essential to the design and optimization of the OHP in real applications. Therefore, by combining the high-speed visualization method and infrared thermal imaging technique, the fluid flow and thermal performance in the OHPs with inner diameters of 1, 2 and 3 mm are presented and analyzed. The results indicate that three fluid flow motions, including small oscillation, bulk oscillation and circulation, coexist or, respectively, exist alone with the increasing heating load under different inner diameters, with three flow patterns occurring in the OHPs, viz. bubbly flow, slug flow and annular flow. These fluid flow motions are closely correlated with the heat and mass transfer performance in the OHPs, which can be reflected by the characteristics of infrared thermal images of condensers. The decrease in the inner diameter increases the frictional flow resistance and capillary instability while restricting the nucleate boiling in OHPs, which leads to a smaller proportion of bubbly flow, a larger proportion of short slug flow, a poorer thermal performance, and easier dry-out of working fluid. In addition, when compared with the 2 mm OHP, the increasing role of gravity induces the thermosyphon effect and weakens the 'bubble pumping' action, which results in a little smaller and bigger thermal resistances of 3 mm OHP under small and bulk oscillation of working fluid, respectively.

In this paper, we present the extension of the pressure-based solver designed for the simulation of compressible and/or incompressible two-phase flows of viscous fluids. The core of the numerical scheme is based on the hybrid Kurganov— Noele — Petrova/PIMPLE algorithm. The governing equations are discretized in the conservative form and solved for velocity and pressure, with the density evaluated by an equation of state. The acoustic-conservative interface discretization technique helps to prevent the unphysical instabilities on the interface. The solver was validated on various cases in wide range of Mach number, both for single-phase and two-phase flows. The numerical algorithm was implemented on the basis of the well-known open-source Computational Fluid Dynamics library OpenFOAM in the solver called interTwoPhaseCentralFoam. The source code and the pack of test cases are available on GitHub: https://github.com/unicfdlab/hybridCentralSolvers

Cancer metastasis into the brain constitutes one of the most severe but not uncommon development of cancer growth. Several factors control how cancer types interact with the brain to establish metastasis These factors include system of migration, system of infiltration of the blood-brain barrier and the interaction with host cells (e.g., neurons, astrocytes) and the immune system fight against metastasis in the brain. Although, brain radiotherapy is the main treatment procedure carried out to treat, new therapies are emerging that constitute a glimpse of hope for increasing the diminutive life expectancy currently forecasted to cancer patients who are facing the prospectus of brain metastasis. However applying these therapeutic strategies has been has not been effective. Thus there is a need for better understanding of the metastasis process in order to suggest novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the various process that they undergo including EMT, penetration of the ECM, intravasation, extravasation and infiltration of the blood brain barrier ending up with colonization and angiogenesis. In each phase, we focus on molecules that could potentially be drug target candidates.

Stroke remains one of the leading causes of death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing ischaemic penumbra. Stem cell therapy offers a promising alternative. As a regenerative medicine, stem cells offer a wider range of treatment strategies, including long-term intervention for chronic patients, through the reparation and replacement of injured cells via mechanisms of differentiation and proliferation. The purpose of this review is to evaluate the therapeutic role of stem cells for ischaemic stroke. The paper discusses the pathology during acute, subacute, and chronic phases of cerebral ischaemic injury, highlights the mechanisms involved in mesenchymal, endothelial, haematopoietic, and neural stem cell-mediated cerebrovascular regeneration and evaluates the pre-clinical and clinical data concerning the safety and efficacy of stem cell-based treatments. Treatment of stroke patients with different type of stem cells appears to be safe and efficacious even at relatively higher concentrations irrespective of the route and timing of administration. Priming or preconditioning of cells prior to administration appears to help augment their therapeutic impact. However, larger patient cohorts and later phase trials are required to consolidate these findings.

Tumors are complex tissues of malignant cells surrounded by a diverse cellular micro-environment with which they interact. The molecular and cellular underpinnings of cancer cells have been increasingly understood during the last few decades. Nonetheless, a great deal remains unknown regarding the ways in which tumour cells modify their surroundings and impact the organisation and makeup of cells. This review aims to concentrate on recent advancements in molecular characterization of tumor cells and its immunology, provides recent and general insight into cancer immunity and immunotherapy, and discusses the immunobiology of human adaptive and innate immunity to malignant growth of cancer cells, the mechanisms that support human immune response from beneath, an up-to-date scientific development to cancer immunotherapy, and how tumor and host responses can Encircle as a military tactic effective anti-cancer immunity.

This article describes the impact of restricting the air intake in industrial 250 m3 WEMCO flotation cells at Los Pelambres concentrator. The influence of this air restriction on the hydrodynamic and metallurgical performance of this type of machine was evaluated. The experiments were conducted in single flotation cells and in entire rougher banks. In all cases, the gas holdup was measured to estimate the effectiveness of the obstruction system to decrease the air concentration. In single cells, axial profiles for solid percentage and particle size were evaluated. In addition, a mass balance was conducted to assess the copper recovery and concentrate features. In individual cells, the air restriction led to a decrease in the gas holdup. However, this slight change was enough to obtain a more stable froth zone and a better solids suspension. The latter was observed as a higher P80 below the pulp-froth interface, a less diluted pulp at this level, a slightly higher Cu recovery, and a coarser concentrate product. A mineralogical analysis of the concentrate sample also showed the presence of coarser liberated Cu-sulfide particles. The results in single cells suggested an improvement in the recovery of coarse particles by a more intense solids suspension. The air intake was also restricted in 3 rougher banks to assess the impact of the air obstruction on the overall performance of the respective circuit. Eleven out of fourteen cells were operated with air restriction, which led to a significant recovery improvement of 0.9%-1.6% (absolute) with a 95% confidence level. Size-by-size mass balances were also conducted for the rougher circuits, which proved that the recovery improvements were justified by the simultaneous increase in the recovery of coarse and fine particles. Thus, a restriction of the air intake showed that the decrease in the gas holdup (and in the bubble surface area flux) was compensated by a better solids suspension and a higher turbulence in the impeller. The former promotes the recovery of coarse particles, whereas the latter improves the interaction between bubbles and fine particles. Further developments are being made to implement a regulatory control strategy to control the air intake in self-aspirated flotation cells, and to use this approach for optimizing industrial flotation banks.

Background: The intrauterine and early extrauterine development represents a “window of opportunity” in the immunological development. The underlying mechanisms are still poorly understood. The aim of this study was to provide reference values B cell subpopulations in cord blood of term newborns, juveniles and in adults to find the spectrum of their physiological age-related variation. Methods: In this study, we used flow cytometry to evaluate human B lymphocytes and subpopulations in cord blood (n = 10), in peripheral blood from healthy juveniles aged 1 to 17 years (n=20) and from donors aged 24 to 62 years (n = 10). Results: Our findings showed increasing frequencies of IgM memory B cells, class-switched memory B cells, marginal zone B cells and plasmablasts, from cord blood to peripheral blood of juveniles and adults. In con-trast, the percentage of naïve B cells was higher in newborns than in juveniles and adults. The frequencies of were similar in cord blood and peripheral blood of adults. Interestingly, transitional B cells frequencies were similar in cord blood and adults but significantly lower in juveniles. Conclusions: The frequencies of circulating B cell subpopulation are subject to considerable changes during on-togeny, reflecting overlying effects of maturation and of the acquisition of an adaptive immune memory.

This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in diabetic retinopathy (DR) Wistar rats, induced to diabetes by intraperitoneal injection with streptozotocin. Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres to obtain the hNPCs, characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell therapy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and verified DR, intravitreal injection of hNPCs (1 x 106 cel/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were done before and after diabetes induction and after cell therapy. Eye enucleation occurred four weeks after treatment for the histopathological and immunohistochemistry analyses. In the treated group, there was the repair of the retinal structures and their arrangements. hNPCs increased the thickness of neuroretina layers, especially in the ganglion cell and photoreceptor layers. The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regeneration of the neuroretinal tissue.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

The focus of the presented work was to isolate and characterize circulating endometrial cells (CECs) enriched from peripheral blood (PB) of patients with diagnosed endometriosis to support endometriosis diagnosis and treatment. Material and Methods Blood samples (n=423) were tested for CECs presence. Subsequently, gene expression analysis (GEA) was carried out for CECs. In parallel, the presence and character of CECs was tested during phases of menstrual cycle (MC) (n= 11). CECs were isolated by size-based separation from 2x 8ml PB. Results CECs were detected in 78.4% of blood samples. In line with the revised American Fertility Society (rAFS) classification CECs presence was confirmed in all the acknowledged endometriosis stages: minimal, mild, moderate and severe. Surprisingly, the highest CEC negativity rate was reported for severe disease (21.1%). The highest CEC numbers were detected in the mid-secretory periods of MC, which corresponds with uterine lining decidualization. The cytomorphology of CECs captured during MC is changing between the epithelial, stromal and stem cell-like. CECs captured in mid-secretory period expressed KRT18, NANOG and VIM in higher amounts when compared to the genes in the proliferative phase of MC when KRT19 and ESR1 were mostly observed. GEA of the super-positive CECs samples (1000 CECs/8mL PB) revealed high expression of KRT18, VIM, NANOG and FLT1. The expression of these genes was elevated in the endometriosis tissue samples and endometrioma, too. Conclusion The panel of the identified CECs - genes could be tested in a prospective manner to confirm the predictive value of CECs in endometriosis diagnostics.

The turbulent Poiseuille flow between two parallel plates is one of the simplest possible physical situations, and it has been studied intensively. In this paper, we propose a modified Prandtl-van Driest mixing length that satisfies both boundary conditions and wall damping effects. With our new formulations, we numerically solve the problem and, moreover, propose an approximate analytical solution of mean velocity. As applications of our solution, an approximate analytical friction coefficient of turbulent Poiseuille flow is proposed.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

Aero-fuel centrifugal pumps are important power plants in aero-engines. Unlike most of the existing centrifugal pumps, a combination impeller is integrated with the pump to improve its performance. First, the critical geometrical parameters of combination impeller and volute are given. Then, the effects of combination impeller on flow characteristics inside the impeller and volute are clarified by comparing simulation results with that of the conventional impeller, where the effectiveness of selected numerical method is validated by an acceptable agreement between simulation and experiment. Finally, the experiment is performed to test the external performance of studied pump. A significant feature of this study is that the flow characteristics are significantly ameliorated by reducing the flow losses emerged in impeller inlet, impeller outlet and volute tongue. Correspondingly, the head and efficiency of combination impeller are higher with comparison to conventional impeller. Consequently, it is a promising approach in ameliorating flow field and improving external performance by applying a combination impeller to an aero-fuel centrifugal pump.

Deformation flows are flows incorporating shear, strain and rotational components. These flows are ubiquitous in the geophysical flows, such as the ocean and atmosphere. They appear near almost any salience, such as isolated coherent structures (vortices and jets), various fixed obstacles (submerged obstacles, continental boundaries). Fluid structures subject to such deformation flows may exhibit drastic changes in motion. In this review paper, we focus on the motion of a small number of coherent vortices embedded in deformation flows. Problems involving isolated one and two vortices are addressed. When considering a single-vortex problem, the main focus is on the evolution of the vortex boundary and its influence on the passive scalar motion. Two vortex problems are addressed with the use of point vortex models, and the resulting stirring patterns of neighbouring scalars are studied by a combination of numerical and analytical methods from the dynamical system theory. Many dynamical effects are reviewed with emphasis on the emergence of chaotic motion of the vortex phase trajectories and the scalars in their immediate vicinity.

Infertility” is a condition defined by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce either as an individual or with his/her partner’. The authors have set out to succinctly investigate, explore and assess infertility treatments harnessing the potential of stem cells to effectively and safely treat infertility, in addition to the legal and regulatory complexities at the heart of stem cell research, with an overview of the legislative state of affairs in six major European countries. In couples who cannot benefit from assisted reproductive technologies (ART) to treat their infertility, stem cells-based approaches have been shown to be a highly promising approach. Nonetheless, lingering ethical and immunological uncertainties require more conclusive findings and data before such treatment avenues can become mainstream and applied large scale. The isolation of human embryonic stem cells (ESCs) is ethically controversial, since their collection involves the destruction of human embryonic tissue. Overall, stem cell research has resulted in important new breakthroughs in the treatment of infertility. The effort to untangle the complex web of ethical and legal issues associated with such therapeutic approaches will have to rely on evidence-based, broadly shared standards, guidelines and best practices to make sure that the procreative rights of patients can be effectively reconciled with the core values at the heart of medical ethics.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

Since its introduction almost 50 years ago, the concept of ‘flow’ has been descriptive of optimal experiences, also in relation to play. However, the explorative nature of play leads to some discrepancies between flow and the optimal experience of play. In this paper the differences between flow and play are explored, leading to proposing the state of ‘wonder’ (directed at exploration) as an alternative to ‘flow’. From this perspective, the study further explores how we may design toys that enable meaningful experiences of play, identifying opportunities in designing for toys as the enablers of immersed experiences of wonder.

There is a long standing ‘two times problem’ in that a satisfactory reconciliation between the time of physics and that of psychology has not been realized. A partial solution to the past/present/future phenomenon has been successfully given by the Hartle information gathering and processing system (IGUS) view. That model IGUS robot is enhanced here for the entire ‘two times problem’ to deal with not only the temporal experiences of the flow of time but also those of manifest time. A dualistic robot is proposed which has a veridical system of temporal experiences that are compatible with various spacetime cosmologies. It also has an illusory system of corresponding temporal experiences. This dualistic IGUS robot was made possible by discovering temporal experience within the brain that correspond to those of physics. The dualistic theory suggests that the veridical system, as a result of evolution, begets the illusory system to enhance behavioral adaptation. Thus, there is just one fundamental physical time which the brain does, indeed, possess and then enhances with illusory counterparts. Therefore, there should no longer be a need to reify illusory temporal experiences as modern spacetime cosmologies tend to do. Physical time already resides within human time.

In this study, the author proposes to evaluate the effect of sales growth, Receivable Turnover and operating cash flow on the liquidity of PT. Unilever Indonesia Plc. The research method used is descriptive method with a quantitative approach. In this statement, the population used in this study is the financial statement data from PT. Unilever Indonesia Plc. from 2010 to 2018, the technique of determining the sampling uses Purposive Sampling. This research data uses secondary data from PT. Unilever Indonesia Plc financial statements from 2010 to 2018. All data sources were obtained from the website of the Indonesia Stock Exchange at https://www.idx.co.id, the company's website and Google search. Our analysis reveals that sales growth and accounts receivable turnover from PT. Unilever Indonesia Plc. has no influence on the liquidity of PT. Unilever Indonesia Plc, while operating cash flow has an influence on the Liquidity of PT Unilever Indonesia Plc. This means the ups and downs of the value of sales and accounts receivable turnover of a company has no influence on the liquidity of PT. Unilever Indonesia Plc, while operating cash flow has increased or decreased has an influence on the liquidity of PT Unilever Indonesia Plc. The value of sales growth, accounts receivable turnover and operating cash flow can explain the liquidity of PT Unilever Indonesia Plc. by 78%, while 22% is explained by other factors which are not included in this study.

Rainfall is the main driver of hydrological processes in dryland environments and characterising the rainfall variability and processes of runoff generation are critical for understanding ecosystem function of catchments. Using remote sensing and in situ data sets, we assess the spatial and temporal variability of the rainfall, rainfall-runoff response, and effects of antecedent soil moisture and ground cover at different spatial scales on runoff coefficients in the Upper Burdekin catchment, northeast Australia, which is a major contributor of sediment and nutrients to the Great Barrier Reef. The high temporal and spatial variability of rainfall exerts significant controls on runoff generation processes. Rainfall amount and intensity are the primary runoff controls, and runoff coefficients for wet antecedent conditions were higher than for dry conditions. The majority of runoff occurred via surface runoff generation mechanisms, with subsurface runoff likely contributing little runoff due to the intense nature of rainfall events. At annual to seasonal temporal scales and for relatively large catchments, we could not detect a significant effect of ground cover on runoff. We conclude that in the range of moderate to large catchments (193 – 36,260 km²) runoff generation processes are sensitive to both antecedent soil moisture and ground cover. A higher runoff-ground cover correlation in drier months with sparse ground cover highlighted the critical role of cover at the onset of the wet season and how runoff generation is more sensitive to cover in drier months than in wetter months. The monthly water balance analysis indicates that runoff generation in wetter months (January and February) is partially influenced by saturation overland flow, most likely confined to saturated soils in riparian corridors, swales, and areas of shallow soil. By March and continuing through October, the soil ‘bucket’ progressively empties by evapotranspiration, and Hortonian overland flow becomes the dominant, if not exclusive, flow generation process. The results of this study can be used to better understand the rainfall-runoff relationships in dryland environments and subsequent exposure of coral reef ecosystems in Australia and elsewhere to terrestrial runoff.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Brain stem cells (neural stem cells or NSCs) and neurons of a chosen kind reprogramming is a potential technique for cell therapy. It is possible to reprogram non-neuronal cells, for example, by using a predetermined group of factors, nuclear transfer, and the induced transcriptional factors (TFs) expression in a related lineage of cells, and non-coding microRNAs (miRNAs). Researchers have additionally been attempting to improve reprogramming methods, whether it is by employing unique sets of biomolecules and particular TFs or by delivering relevant miRNA and Biomolecules. The technique of miRNA mediated is intriguing for its capability to quickly create a range of biologically desirable cell types for therapy from different lineages of cells. Current findings have made significant advancements towards changing the somatic cells to diverse particular neuronal subgroups with greater efficiency, using reprogramming of miRNA-mediated neural cells, despite the fact that the precise processes need to be discovered. To further understand how miRNAs might direct somatic cells to become neural, we need to look at the latest research on their function in neural reprogramming over the differentiated cells. Recent findings on the role of miRNAs in the initiation of cell reprogramming and the determination of the neuronal subtype's destiny are the primary focus of this comprehensive overview. Furthermore, we cover the far more latest results concerning certain miRNAs' activity in controlling different phases of neuronal differentiation, which contributes in comprehending the interaction network of miRNAs and their receptors.

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

The role of circulating plasma cells (CPCs) and circulating leukemic cells (CLCs) as biomarkers for several blood cancers, such as multiple myeloma and leukemia, respectively, have recently been reported. These markers can be attractive due to the minimally invasive nature of their acquisition through a blood draw (i.e., liquid biopsy) negating the need for painful bone marrow biopsies. CPCs or CLCs can be used for cellular/molecular analyses, such as immunophenotyping or fluorescence in situ hybridization (FISH). FISH, which is typically carried out on slides involving complex workflows, becomes problematic when operating on CLCs or CPCs due to their relatively modest numbers. Here, we present a microfluidic device for characterizing CPCs and CLCs enriched from peripheral blood using immunofluorescence or FISH. The microfluidic possessed an array of cross-channels (2-4 µm in depth and width) that interconnected a series of input and output fluidic channels. Placing a cover plate over the device formed microtraps, the size of which was defined by the width and depth of the cross-channels. This microfluidic chip allowed for automating immunofluorescence and FISH requiring the use of small volumes of reagents, such as antibodies and probes, as compared to slide-based immunophenotyping and FISH. In addition, the device could secure FISH results in <4 h compared to 2-3 d for conventional FISH.

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICC) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric-emptying. Regenerating these fundamental structures with stem cell therapy, would be helpful to restore gastric function in GP. Mesenchymal stem cells (MSC) have been successfully used in animal models of other gastrointestinal (GI) diseases including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored if mouse MSC can be delivered from a hydrogel-scaffold to the luminal surfaces of GP mice stomach. Mouse MSC was seeded atop alginate-gelatin, coated with poly-L-lysine. These cell-gel constructs were placed atop stomach explants facing the luminal side. MSC grew uniformly all across the gel surface within 48 hr. When placed atop the lumen of the stomach, MSC migrated from the gels to the tissues as confirmed by positive staining with Vimentin and N-cadherin. The feasibility of transplanting a cell-gel construct to deliver stem cells in the stomach wall was successfully shown in a mice GP model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with stem cells, and growth factors.

The adipose-derived mesenchymal stem cells are becoming the tool of choice for many clinical applications and nowadays, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type for many diseases and pathological conditions. To reach the goal of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize the GMP processes and thus collection methods, transportation strategies, extraction protocols and characterization procedures without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability genetically determined and acquired during life. Here we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. Variability in the age of patients, gender and laboratory parameters like total cell number, cell viability, stem cell number and other stromal vascular fraction cell sub-populations have been compared to each other. Results show that, when the laboratory protocol is standardized, the variability in quantifiable cell parameters is widely statistically non-significant, meaning that we can make a further step toward standardized advanced cell therapy products.

Maxwell equations governing electromagnetic effects are being shown to be equivalent to the compressible inviscid Navier-Stokes equations applicable in fluid dynamics and representing conservation of mass and linear momentum. The latter applies subject to a generalized Beltrami condition to be satisfied by the magnetic field. This equivalence indicates that the compressible inviscid Navier-Stokes equations are Lorentz invariant as they derive directly from the Lorentz invariant Maxwell equations subject to the same Beltrami condition. In addition, the derivation results provide support for the claim that electromagnetic potentials have physical significance as demonstrated by Aharonov-Bohm effect, and are not only a convenient mathematical formulation.

Temporary streams are a key component of the hydrological cycle in arid and semi-arid regions, but their flow is highly variable and difficult to measure. In this paper, we present a novel approach that could be used to assess the flow of temporary streams and characterize their environmental status. Specifically, we apply the Image Velocimetry method to estimate surface velocity in temporary streams using unmanned aerial vehicles (UAVs) equipped with optical sensors (IV-UAV method). The IV-UAV method enables the easy, safe and quick estimation of the velocity on the water’s surface. This method was applied in different temporary streams in Lesvos Island, Greece. The produced results show that the IV-UAV can be implemented at low discharges, at temporary streams and at small streams. However, there were many occasions that measurements were unable due to various reasons such as dense vegetation or archaeological sites. Despite of this, the proposed methodology could be incorporated in optical protocols which are used to assess the environmental status of temporary streams of Mediterranean conditions. Finally, this would become a valuable tool for understanding the dynamics of these eco-systems and monitoring changes over time.

The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induced the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In the present study, we aimed to explore the signaling pathway in BM cells responsible for MDSC generation. RNA-seq revealed that the mitogen-activated protein kinase (MAPK) pathways, among biochemical pathways, exhibited the highest number of differentially expressed genes in BM cells with MSC coculture relative to those without. Western blot confirmed strong phosphorylation of c-Jun N-terminal kinase (JNK) in BM cells cocultured with MSCs under GM-CSF stimulation, whereas p38 kinase activation remained unaltered by MSCs. Inhibition of JNK by SP600125 significantly abolished the expression of Arg1 and Nos2, the hallmark genes of MDSCs, as well as Hif1α, a molecule mediating monocyte functional re-programming into suppressive phenotype, in MSC-cocultured BM cells, while increasing TNF-α in response to lipopolysaccharides stimulation. Furthermore, JNK inhibition markedly abrogated the effect of MSCs on the production of TGF-β1, TGF-β2 and IL-10 in BM cells. These results suggest that MSCs induce MDSC differentiation in BM during inflammation, at least in part, through the activation of the JNK MAPK signaling pathway.

Since the past few decades, numerous modifications and innovations have been done to design the optimal corneal biomatrix for corneal epithelial cells (CECs) or limbal epithelial stem cells (LESCs) carriers. However, researchers have yet to discover the ideal optimization strategies in the development of corneal biomatrix design and its effects on cultured CECs or LESCs. This review further discusses and summarizes recent optimization strategies to develop an ideal collagen biomatrix and its interaction with CECs and LESCs. Using PRISMA guidelines, the articles published from June 2012 to June 2022 were systematically searched using Web of Science (WoS), Scopus, PubMed, Wiley, and EBSCOhost databases. The literature search identified 444 potential relevant published articles, with 29 relevant articles selected based on the inclusion and exclusion criteria after the screening and appraising processes. The current paper highlights the physicochemical and biocompatibility (in vitro and in vivo) characterization methods, which were inconsistent throughout the different studies. Despite the variability in the methodology approach, the reviewer postulated that the modification of the collagen biomatrix improves its mechanical and biocompatibility properties toward CECs and LESCs. All findings were discussed in this review; thus, it provides a general view of up-to-date trends in this field.

Hippocampus plays a crucial role in spatial and episodic memory. The acquisition of new memories is impossible without participation of the hippocampus. There are two main functional states or “modes” of the hippocampal activity, theta and non-theta state. They have different behavioral correlates and clearly different spectral content of the LFPs and neuronal spiking. Hippocampal theta state is present under active exploratory behavior, locomotion, cognitive situations requiring attention and REM sleep. Slow-wave sleep and quiet wakefulness (immobility, eating, grooming) represent the non-theta hippocampal state. The nodal point for the regulation of hippocampal activity is the MS. The activation or suppression of different types of MS cells appears to be responsible for controlling hippocampal theta and non-theta states. Functional coupling between MS neurons and hippocampal interneurons varies in a state-dependent manner.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

Nowadays the positive immune involvement in the eradication of tumor cells is assigned to the adaptive immune response. By awakening of in vivo responding T cells that are suppressed by the tumor and prevents immunological cure of the cancer. The adaptive immune response is a complex of different cells and protein molecules. Normally activated T cells are well-ordered by several late occurring inhibitors to contain the response to the unknown invaders and spare the normal cells. The tumor strengthens this inhibitory response to escape from immune elimination. Immunotherapy is to unleash the full capacity of the adaptive immune system by blocking this inhibitor response by monoclonal antibodies but with the potential drawback of autoimmune phenomena. Seen the success of the immunotherapy another feature of the immune system is overlooked. Cytokines and chemokines became in oblivion after their suspected necrosis of the tumor (TNF) did not fulfil their initial hope. When patients seek help for their complaints the ovarian cancer is in most cases already metastasized to the peritoneum and omentum. Here, we show that on the one hand chemokines produced by Th2, CD8 and NK cells inhibit cancer spreading and thus leads to a better operability and thus better survival. On the other hand, chemokine receptors are expressed by the tumor that are a decoy by binding chemokines that normally should attract antigen cross-presenting dendritic cells, which start an adaptive T cell response.

Inflammatory bowel disease (IBD) is a CC chemokine receptor 6 (CCR6) - associated immune mediated disorder which has attracted an extensive superfluity of experimental analyses. IBD has come to the fore of varied scrutinizing owing to its complexity by nature for comprising of two synergistic sub phenotypes; Crohn’s disease (CD) and Ulcerative colitis (UC). Both these disease entities cause potent immune dysregulation followed by intense tissue damage within the gut mucosal system, initiating symptoms which are severely debilitating. Multiple causative factors are said to be responsible for IBD but direct immune dysfunction is kindled by overplay of innate and adaptive immune responses produced against a pathogenic microbial attack through the weakened or leaky gut epithelial barrier. Once immune homeostasis is not achieved by tolerating agents, the self-assertive adaptive immunity mobilize its various T and B cell cohorts initializing their allied immune mechanisms by vigorously deploying them towards the site of infection. CCR6 and its unique solitary ligand CC-chemokine ligand 20 (CCL20) are small protein molecules which are abundantly expressed by T and B lymphocytes and act as chemotactic immune-modulatory envoys that help in the deployment of the effector lymphocyte arm of the immune system, producing two directly opposing outcomes in IBD. This dichotomous immunity consists of either immune tolerance or inflammation which then develops into a chronic state, remaining catatonic to inherent immunity or targeted clinical therapy. In this review, we have chronologically identified a plethora of experimental studies radiating into 14 different compartments highlighted in the visual depiction which have employed both mouse models and clinical subjects spanning a period of nearly two decades. In doing so, we expect the research community would further benefit by tracing through the history, thereby understanding the CCR6 –CCL20 axis in IBD and identifying the gaps in literature which can be fortuitously filled in the future.

Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.

Abstract: Presence in a recipient of antibodies directed against donor specific antigens represent a major obstacle in transplanting such patients. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques and old and new drugs are to date used to desensitize these patients. Desensitization may occur before transplantation or at the time of transplantation or after transplantation according whether physicians deal with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivity and specificity, different advantages and disadvantages. The target of the drugs used to desensitize are B cells, Plasma cells, the antibodies themselves and finally, the complement that is the final actor causing tissue disruption. If B cells are relatively easy to be targeted, more difficult are the plasma cell. Indeed, several new drugs are used in randomized trials also to defeat plasma cells. Antibodies may be removed rather easily, but often their removal is followed by a rebound. Complement is not easy to be defeated and new drugs are to date used to be successful in this action. However is to date possible to desensitize many patients and to obtain successful transplantation.

The discrete element method (DEM) coupled with computational dynamics (CFD) has been considered one of the most sensitive ways of studying fluidized beds. This paper presents gas-solid fluidized bed simulations by use of CFD-DEM. The two-phase interaction is calculated in a way of decoupling. Within the effective neighborhood of the particles, the kernel approximation method is used to calculate the local porosity, thereby calculating the drag force on the particles. At the grid scale, the momentum exchange coefficient is calculated using a two fluid model based method, thereby calculating the source term of the phase interaction in the fluid control equation. The simulated form, size and motion process of the big bubble are all consistent with experimental observations. The simulated solid volume fraction and relative pressure averaged in a horizontal plane at 45 mm above the bottom are in reasonable agreement with the experimental data. The fluctuation of the simulated bed height over time is similar to the experimental measurement results. The reproduction of these qualitative and quantitative results indicates that the proposed method effectively improves simulation performance and accuracy.

Active flow control is a promising technology for reducing noise, emissions, and power consumption in various applications. To better understand the performance of synthetic jet actuators, a computational model that couples structural mechanics with electrostatics, pressure acoustics, and fluid dynamics has been needed. The model presented here has been validated against experimental data and then used to investigate the fluid behavior inside and outside the synthetic jet actuator cavity, impacts of thermoviscous losses on capturing the acoustic response of the actuator, and viability of different modeling methods of diaphragms in computational simulations. The results capture the feedback from the fluid onto the diaphragm and highlight the need for careful acoustic modeling.

Material and methods. The trial was carried out over two years in Southern Italy. Two grapevine rootstocks, 110R and SO4, were compared to evaluate the water extraction ability from the soil and the effect on the yield and quality of the Cardinal grapevine table cultivar. Therefore, a new approach to plant water consumption based on sap flow was adopted. Results. The earlier and faster water refilling of the xylem in Cardinal onto 110R (C/110R) appears responsible for the earlier evolution of the phenological phases than Cardinal onto SO4 (C/SO4). The maximum length of the principal shoot was reached in Cardinal/110R compared to C/SO4, while a higher number of lateral shoots with lower internode has changed canopy architecture and light distribution in C/SO4. The 110R used more water compared to SO4; it was possible to quantify the real transpired flux of the plant per day: sap flow was 12.3 L.plant-1.d-1 and 11.7 L.plant-1d-1 in C/110R in the first and second year, respectively, while it was 14% lower in alternative graft combination. Conclusions. However, C/SO4 was able to sustain leaf water status and physiological mecha-nisms, although with lesser performance than C/110R, but that did not cause negative effects on production parameters.

With the wide application of flow sensor, their reliability under extreme conditions has been concerned in recent years. The reliability of a Micro Electro Mechanical Systems flow sensor under temperature (Ts) is researched in this paper. Firstly, the Step-stress accelerated degradation test is designed. Because this flow sensor consists flow sensor chip and signal processing system, the accelerated degradation testing is implemented, respectively. While the results show that the biggest drift is 3.15% for flow sensor chips with 150℃ conditions, and 32.91% for this flowmeter. By analysis, it could be found that the attenuation of the signal processing system is significant to the degeneration of this flowmeter. The minimum drift of the signal processing system accounts for 82.01% of this flowmeter. Secondly, using the Coffin-Manson model, the relationship between cycle-index and Ts is established. And the lifetime with different Ts is estimated by the Arrhenius model. In addition, the Weibull distribution is applied to evaluate the lifetime distribution. Finally, the reliability function of the Weibull distribution is demonstrated, and the survival rate within one year is 87.69% with 85℃ conditions. Thus, by the application of accelerated degradation testing, the acquired results are innovative and original. This research illustrates the reliability research, which provides a relational database for the application of this flow sensor.

Background: Poor patient flow can lead to adverse outcomes for patients and organisational inefficiency. Many hospitals have addressed suboptimal patient flow by increasing resourcing, such as bed stock and staffing, however, this is an unsustainable approach. In determining the nature of poor patient flow issues, it is important to collect data from healthcare professionals who manage patient flow on a daily basis. Doing so provides insights into the current state of patient flow management in its entirety, whilst also helping with the development of sustainable solutions.; Methods: Thirteen semi-structured interviews were conducted with clinicians who were directly involved with patient flow at a tertiary care centre in Tasmania, Australia. Results: Through a thematic analysis method, four major themes were developed: managing patient flow, communication for decisions, tools as enablers and barriers and increasing complexity. Conclusions: The findings of this study provide great insights into patient flow issues, with potential solutions identified to address them.

This paper presents the results of simulations of particle-laden air-solid jet flow in long straight tubes using CFD-DEM, along with an analysis of coarse-graining. Although previous studies have used CFD-DEM for similar flows, these have typically been in a dilute flow regime where uncoupled simulations are accurate. However, fully coupled simulations can introduce issues, necessitating validation studies to ensure that all coupling parameters are effectively used and that the physics is accurately represented. This paper validates the simulations against two different experimental studies, with fluid Reynolds numbers between 10,000 and 40,000 and Stokes numbers between 5.6 and 50. Interestingly, the profiles of mean particle velocity exhibit fewer discrepancies as the Stokes number increases but more discrepancies for the root mean square velocity compared to the experiments. Particle number flux is consistent with the experiments after the nozzle exit. Coarse-graining is also applied to the same simulations, achieving relatively accurate results. However, as expected, scaling of contact collision frequencies, forces, and stresses cannot be achieved, meaning that coarse-graining may be useful for comparing designs or operating parameters on an industrial scale but falls short when measuring the total energy dissipation of one experiment.

Gas embolism is a medical condition leading to the blockage of blood flow in the microvasculature by gas bubbles. While reported as rare, gas embolism often has devastating, fatal physiological consequences. Despite this acute importance, the genesis and evolution of air bubbles in blood vessels under different physiological conditions, such as blood viscosity and blood flow rate, is still understudied, largely because of difficult experimentation and in situ visualization. The objective of this work was to study the gas embolism phenomenon in vitro, using a microfluidic system that mimicked the architecture of microvasculature. The microfluidic systems comprised linear channels with two different air inlet types, namely, T- and Y-junctions with three different widths (20 µm, 40 µm, and 60 µm), and a 30 µm width honeycombed network with three bifurcation angles (30°, 60°, and 90°). Three synthetic liquids equivalent to 0%, 20%, and 46% hematocrit that mimicked the physiological blood viscosity and hematocrit concentrations were used. Our results show that: (i) 20 µm and 40 µm width channels had an elevated risk of gas embolism due to wide fluctuations in the total slug sizes; (ii) the resistance to the flow of air bubbles increased with the increase in the equivalent concentration of hematocrit; (iii) gas bubbles causing blockages and dampening of the flow velocity were frequently observed in 20 µm channels, and lastly (iv) increased risk of gas embolism was observed in the honeycomb architecture with 60° and 30° bifurcations. This work suggests that in vitro experimentation using microfluidic devices with microvascular tissue-like structures opens the possibility of studying this medical condition with high reproducibility and impacts the fact-based medical guidelines for preventing or mitigating iatrogenic occurrences.

This paper presents an analysis of linear viscous stress Favre-Averaged turbulence models for computational fluid dynamics (CFD) of fully turbulent round jets with a long straight tube geometry in the near field. Although similar work has been performed in the past with very relevant solutions, considerations were not given for the issues and limitations involved with coupling between an Eulerian and Lagrangian phase, such as in fully two-way coupled CFD-DEM. These issues include limitations on solution domain, mesh cell size, wall modelling, and momentum coupling between the two phases in relation to the particles size. Therefore, within these considerations, solutions are provided to the Navier-Stokes equations with various turbulence models using a three-dimensional wedge long straight tube geometry for fully developed turbulence flow. Simulations are performed with a Reynolds number of 15000 and 50000 using two different tube diameters. It is found that a modified k−ε turbulence model achieved the most agreeable results for both the velocity and turbulent flow fields between these two flow regimes, while a modified k−ω SST/BSL also provided suitable results.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24hour urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005 respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24hour urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005 respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

Magnesium (Mg) deficiency may be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim was to determine the acute effect of an oral Mg supplement compared to control on endothelieal function assessed by flow-mediated-dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9kg/m2) completed this randomised cross-over study. Blood pressure (BP) and FMD were measured and blood samples taken before participants drank 200ml water with or without an over the counter Mg supplement (450mg and 300mg for men and women). Measurements were repeated at 60 and 120 minutes. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = .037). A difference of -0.085mm in FMD was observed 60 minutes post drink in the control group compared to baseline FMD, and no difference was observed in the supplement group compared to baseline. Despite the non-significant interaction between treatment and time on FMD, the difference seen in the control group and the lack of change in the supplement group at 60 minutes post-drink suggests that Mg may attenuate the reduction in FMD post-prandially.

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2±1.3% (n = 3) and radiochemical purity &gt;90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6±3.6% (n = 3) with an equivalent RCP &gt;90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus, and optimisation of the method is required before the flow process is competitive with manual reactions.

The objective of this work is to evaluate the impact of the innovative modifications made to the conventional effluent capture and discharge devices used in subsurface flow wetlands (SSFW). The main modifications developed consist on extending the influence of the capture and discharge device in such a way that the SSFW width and height are fully covered. This improved innovative device was applied and evaluated in two subsurface flow wetlands, one on a pilot scale and one on a real scale. To evaluate the impact of the innovative device with respect to conventional one in the operational functioning of subsurface flow wetlands, the elimination of chemical oxygen demand was measured and compared. The results show that for the innovative device, the COD removal was 10% higher than for the conventional device, confirming the validity and effectiveness of the modifications implemented in the effluent capture and discharge devices used in SSFW.

The hydrodynamic results obtained from the permeability of porous materials not only affect the assessment of the stream of the gas flow through those materials but they also refer to the loss of pressure energy in that flow. The direct measure of that loss is flow resistances.The results of experimental research upon the assessment of the flow resistances of porous materials with respect to gas flow. The research conducted applied to natural materials with an anisotropic gap-porous structure. The tests were carried out on a gas permeability measuring system, adapted to different shapes of porous material samples. The process issue of the total pressure drop on a porous deposit was considered in the Reynolds number category. The coefficient of flow resistance for anisotropic materials was defined and the value of this coefficient was compared to the gas stream and the total pressure drop on the porous bed was experimentally evaluated.

Simulation programs contain Computational Fluid Dynamics - CFD codes and are a useful tool used for gas flow through porous materials. Conducting numerical simulations allows for detailed analysis of hydrodynamic phenomena. The results of numerical modeling should always be verifiable based on experimental data. Only their compliance with the results of experimental tests is a determinant of the correctness of the applied method. As part of the work, experimental studies of hydrodynamics of gas flow through an isotropic porous material were carried out and numerical simulation for material of the same shape was used. In the CFD modeling Kolmogorov's hypothesis for the transport of kinetic energy of turbulence k and transport of dissipation rate of kinetic energy of turbulence ε was used.

The aim of this work is to evaluate the impact of proposed modifications to conventional capturing and discharging effluents devices in Subsurface Flow Wetland (SSFW) systems. Main modifications proposed consist on extending the influence of the capture and discharge device in such a way that the SSFW width and height are fully covered. Additionally an SSFW prototype was built as pilot including the proposed modifications and the impact of the innovative device is measured based on the efficiency of the Chemical Oxygen Demand (COD) removal as compared to a traditionally built SSFW. The results show that for the innovative device, the COD removal was 10% higher than for the conventional device.

In this paper, we studied and analyzed the behavior of velocity profiles and the distribution of pressures in a pipe connected to an accessory. In this case, it was a 90º elbow fitting in which water flows as an incompressible flow. This study was developed numerically through the fluent program of ANSYS. It is of practical interest in engineering because it is based on results regarding the internal structure of a model of incompressible flows. In the same way, it provides a basis for the proper design and implementation of velocity profiles within an elbow.In the agricultural industry, suitable systems can be implemented for crop irrigation in this way with the results obtained to improve the design in the fluid distribution system.We used a feasible κ-ε turbulence model because this model causes less turbulence than the standard κ-ε model. A mesh independence study was developed, in which it was observed that combining different densities of meshes for the same geometry causes some variables, so a fine meshing was used to carry out the study so that the results are as close to reality as possible.