Respiratory distress syndrome (RDS) is a major respiratory morbidity associated with prematurity. In this case-control study, we prospectively evaluated whether targeted metabolomic analysis (gas chromatography–mass spectrometry) of the gastric fluid obtained from very preterm neonates (< 32 weeks’ gestation) during the first hour after birth could predict the need for exogenous surfactant for the treatment of RDS. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants with mild or no RDS (controls) who were not treated with surfactant. Perinatal and neonatal characteristics were recorded. Univariate analysis showed significant differences between the two groups in gastric fluid metabolites (L-glycine and acetyl-L-serine) and clinical parameters (gestational age, 1- and 5-minute Apgar scores, and intubation in the delivery room). Moreover, multivariate analysis revealed intubation in the delivery room as the most potent clinical predictor of surfactant administration [AUC of 0.69 (95% CI 0.57-0.81)]. The combination of metabolomic and clinical data allowed for the construction of a model with good accuracy [AUC 0.76 (95% CI 0.64-0.86)] in predicting surfactant replacement therapy. Further research is required to explore the role of gastric fluid metabolomics in the prediction of RDS and other neonatal outcomes.

This study proposes a customized industrial nozzle for generating impulsive air jets. It is installed on an automatic machine where wine caps are stacked and shot consecutively into a rotating cylinder by an air jet. This process is very noisy; hence, this study aimed to investigate possible geometric variations of the nozzle that can reduce the emitted noise. First, the nozzle was tested in a laboratory to measure the air consumption at different supply pressures. Subsequently, 3D models of the nozzle and its variations were created and used for computational fluid dynamics simulations. Different boundary conditions were set, first to validate the model and compare it with the experimental test results, and then to simulate the real working conditions and determine the geometry that is less noisy while maintaining the velocity peak. Among the various possibilities, shortening the final ducts of the nozzle appears to be the most promising solution. These modified nozzles could be easily added to current machines to provide immediate benefits, and this study represents a promising start for action on other machines where this type of device is present.

Oil and Gas companies, both national and international, along with government regulators, share a common goal of efficiently managing their valuable assets. These assets refer to the Reserves of oil and Gas located underground. Typically, production and Reserves Engineers play a crucial role in managing these reserves through the implementation of well testing techniques. Thus far, the gold standard in this field has been to ensure the optimal management and utilization of these resources. In the context of well testing, the separator has traditionally been considered the gold standard. However, despite regulatory mandates for frequency of well testing (Such as the general requirements of every 30days in the Nigeria south East zone sector), There is a lack of specific regulations regarding the expected flow measurement uncertainties. This gap in the regulations leaves room for improvement in establishing guidelines for accurate flow measurements. This paper aim to Review the various test separator employed, examine the implications of the 30days testing interval under real - world conditions, and critically assess the achievable measurements uncertainties in the field. Additionally, it will provide a candid analysis that sheds light on the expected uncertainties associated with flow measurements. The introduction of the multiphase meters in the past two decades hold the potential for significant advancements in Reservoirs management performance. However, the authors suspect that this potential has not been universally realized. This paper aim to address this issue by examining the extent to which the benefits of multiphase meters have been effectively utilized in reservoir management. By doing so, it seeks to shed light on any existing gaps and propose recommendation for maximizing the impact of multiphase metres in the field. In addition to the aforementioned objectives, this paper will also address and explore the following key aspects:Identification and review of both the strength and weaknesses associated with test separators. By thoroughly examining these attributes, we can gain valuable insight into their effectiveness and potential areas for improvement. Exploration of alternative application of test separator and their impact on well testing efficiency. Real -World comparison will be provided to highlight the advantages and challenges associated with these alternative uses, offering a comprehensive understanding of their implications. Evaluation of the contribution that multiphase flows meters (MPFMs) can bring to the testing scenario and overall performance. By assessing the capabilities and potential benefits of MPFMs, we aim to provide a comprehensive picture of their role in enhancing testing procedures. Examination of the flow measurement uncertainties that can be expected from a test separator and their potential impact on reservoirs management performance. By understanding and quantifying these uncertainties, we can gain insight into how they may affect decision -making and optimization strategies in managing our materials assets effectively. Delving into the question of reconciling multiphase flow meter (MPFMs) with test separators. This analysis aims to inject a sense of realism into the world of managing our major material assets by explaining the challenges and opportunities associated with integrating and aligning these two measurement technologies. By addressing these crucial aspects, this paper strives to provide a comprehensive understanding of the complexities involved in managing our material assets, ultimately driving towards more informed decision-making and improved performance.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

This prospective study aimed to evaluate the ability of point-of-care Doppler ultrasound measurements of carotid-corrected flow time and changes in corrected carotid flow time (FTc) induced by volume expansion to predict fluid responsiveness in patients undergoing robot-assisted gynecological surgery in a modified head-down lithotomy position. FTc was measured using Doppler images of the common carotid artery before and after volume expansion. The stroke volume index at each time point was recorded using the MostCare instrument. Fluid responsiveness was defined as a stroke volume index ≥10% increase after volume expansion. Half (50%) of the 52 patients responded positively. The areas under the receiver operating characteristic curves measured to predict fluid responsiveness for the corrected carotid flow time and changes in the FTc were 0.82 [95% confidence interval:0.705–0.937; P &lt; 0.0001] and 0.67 (95% confidence interval:0.520–0.815; P &lt; 0.05), respectively. The optimal cut-off value for the FTc and the change in FTc were 356.5 ms and 19.5 ms, respectively. FTc is a more reliable predictor of fluid responsiveness than FTc induced by volume expansion in gynecological patients undergoing robot-assisted laparoscopic surgery in the modified head-down lithotomy position.

Hydatid cyst fluid is a complex biological substance consisting primarily of water, proteins, lipids, carbohydrates, salts, enzymes, hormones, growth factors, immune modulators, and other bioactive molecules. Antigens, including antigen B (AgB) and antigen 5 family members (Ag5), have been identified in hydatid cyst fluid and have been shown to have the ability to inhibit cancer progression. The exact mechanisms by which these components exert inhibitory effects on cancer progression are not fully understood, but it is believed that they may influence multiple signaling pathways involved in cell proliferation, survival, angiogenesis, and metastasis. In vitro studies have demonstrated that treatment with hydatid cyst fluid or specific antigens can inhibit cell growth, induce apoptosis, and suppress the migration of cancer cells. Animal model studies have also demonstrated significant inhibition of tumor growth, reduction in angiogenesis, and suppression of metastasis. Limited clinical studies have shown promising outcomes, including improved overall survival and reduced recurrence rates among breast cancer patients receiving AgB immunotherapy alongside standard treatment.

In this study, the motion characteristics of soft alginate microrobots were investigated with wireless magnetic fields in complex fluidic environments. Our aim is to explore the various motion modes that arise as a result of shear forces in viscoelastic fluids. Polyacrylamide (PAA), a water-soluble polymer, was characterized to produce a dynamic environment with a non-Newtonian fluid. The robots were fabricated by an extrusion-based microcentrifugal droplet method. We successfully demonstrated the feasibility of both wiggling and tumbling motions using snowman-shaped microbots. It is found that wiggling motion is primarily influenced by the interaction between the viscoelastic fluid environment and the non-uniform magnetization of the microbots. Additionally, it is discovered that modifying the viscoelasticity properties of the fluid can affect the motion behavior of the microbots. Furthermore, we observed that swarms of microbots exhibit non-uniform behavior within complex environments. Our velocity analysis has provided valuable insights into the relationship between applied magnetic fields and motion characteristics, enabling a more realistic understanding of surface locomotion in the context of targeted drug delivery.

Prediction of survival in very preterm infants is very important in terms of clinical medicine and parent counseling. In this prospective study involving 96 very preterm infants, we evaluated whether metabolomic analysis of gastric fluid and urine samples obtained soon after birth could predict survival on days of life (DOL) 3 and 15 as well as overall survival up to hospital discharge. Gas chromatography-mass spectrometry (GC-MS) profiling was used. Uni- and multivariate statistical analyses were carried out to evaluate significant metabolites and their prognostic value. Differences in several metabolites were identified between survivors and non-survivors at the time-points of the study. Binary logistic regression showed that certain metabolites in the gastric fluid including arabitol as well as succinic, erythronic and threonic acids was associated with DOL 15 and overall survival. Gastric glyceric acid was also associated with DOL 15 survival. Urine glyceric acid could predict survival on DOL 3 and overall survival. In conclusion, non-surviving preterm infants showed a different metabolic profile compared survivors showing a significant discrimination with the use of GC-MS-based gastric fluid and urine analysis. Results of this study support the usefulness of metabolomics in developing survival biomarkers in very preterm infants.

The main objective of this study is to demonstrate proof of principle that computational fluid dynamics (CFD) modeling is a tool for studying the contribution of covert and overt vascular architecture to the risk of cerebrovascular disease in in sickle cell disease (SCD) as well as uncover one or more mechanism of response to therapy such as chronic red blood cell (cRBC) transfusion. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial, using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific potions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral artery such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arm. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had SCI) that developed neurovascular outcomes. CFD approaches allows for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions.

Biology is about structure. Structures within structures. Organs within animals, tissues within organs, cells within tissues, and molecules, often proteins within cells. The structures are so complex that they can only be described by numbers. No numbers are of more importance than those that describe proteins. The numbers that describe coordinates of its atoms, often determined by Patterson functions (which are inverse Fourier Transforms of intensities) of crystal diffraction. Without these numbers, structural biology would hardly exist. Without numbers, engineering would not exist. Numbers are surely needed by the engineers who produce the x-rays diffracting from atoms of protein crystals. Devices of engineering have function. They are built to implement equations. Engineering devices use structures to implement equations, when power is supplied at the right places, that produces appropriate flows. Flows are the essence of life. Equilibrium means death in most living systems. Flows in biological structures are hard to analyze because we do not know input output equations in advance. Sometimes we do not know their function. Flows, forces, and structures of life (like those of engineering) are related by field equations of conservation laws, partial differential equations, constrained by location and properties of structures. Constraints are boundary conditions located on the complicated domain of biological structure. Dealing with this complexity is simplified if one systematically analyzes structure using the most general field theory known, electricity described by the Maxwell equations, without significant known error. Currents are involved because flows of biology usually involve migration of charges, convection of water and solutes, diffusion of ions that form the plasma of life, and their interactions. Interactions can dominate function. Here I show how a few complex structures can be understood in engineering detail. This approach may be useful in dealing with biological and medical issues in many other cases. In one limited case—the clearance of a toxic waste (potassium ions) from the optic nerve—this approach seems to have succeeded.

In this paper, a method of direct spinning is proposed for direct spinning of heterogeneous spun wire-blown holes standard parts and the motherboard mounted on the spin board assemblies. The standardization of the spinneret hole was conducive to improving the machining accuracy and efficiency of the pores, and the spinneret holes could be replaced in time when a hole in the spinneret fails. Moreover; on the other hand, according to the needs of the process of spinning, the spinnerets with various cross-sections were combined and installed on the same motherboard for spinning, and the spinning obtained different bionic new functional products. Based on the results, a finite element model of the standard part of the spinneret hole was developed, and the spinnability of the combinable spinnable spinneret board was verified by simulating the melt flow in the spinneret channel through POLYFLOW software. Further, by the processing of the spinneret, the motherboard was installed into a combined spinneret, and the spinneret assembly was installed on the spinning machine for the experiments. Furthermore, the tow section was observed using a microscope, and the results showed the feasibility of the proposed method.

Docked ships are a source of contamination for the city while they keep their engine working. Plumes emissions from large boats can carry a number of pollutants to the nearby cities causing a detrimental effect on the life quality and health of local citizens and ecosystems. A computational fluid dynamics model of the harbour area of Tromsø has been built in order to model the deposition of CO2 gas emitted by docked vessels within the city. The ground level distribution of the emitted gas has been obtained and the influence of the wind speed and direction, vessel chimney height, ambient temperature and exhaust gas temperature has been studied. The deposition range is found to be the largest when the wind speed is low. At high wind speeds, the deposition of pollutants along the wind direction is enhanced and spots of high pollutant concentration can be created. The simulation model is intended for the detailed study of the contamination in cities near the coast or an industrial pollutant source of any type of gas pollutants and can easily be extended for the study of particulate matter.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

In a thin-volume photobioreactor where a concentrated suspension of microalgae is circulated throughout the established spatial irradiance gradient, microalgal cells experience a time-variable irradiance. Deploying this feature is the most convenient way of obtaining the so-called “flashing light” effect, improving biomass production in high irradiance. This work investigates the light flashing features of sloping wavy photobioreactors, a recently proposed type, by introducing and validating a Computational Fluid Dynamics model. Two characteristic flow zones (straight top-bottom stream and local recirculation stream), both effective toward light flashing, have been found and characterised: a recirculation-induced frequency of 3.7 Hz and straight flow-induced frequency of 5.6 Hz were estimated. If the channel slope is increased, the recirculation area becomes less stable while the recirculation frequency is nearly constant with flow rate. The validated CFD model is a mighty tool that could be reliably used to further increase the flashing frequency by optimising the design, the dimensions, the installation and the operational parameters of the sloping wavy photobioreactor.

This paper investigates the tank drainage problem of an isothermal, unsteady, incompressible electrically conducting Power law fluid. Analytic solution have been obtained from governing continuity and momentum equations subject to appropriate boundary conditions by using Perturbation method. The Power law fluid model solution without MHD is retrieved from this proposed model on substitution . Declaration on behalf of velocity profile, volume flux, average velocity, connection of time with respect to length of the tank and requirement of time for whole drainage of fluid are acquired. Special effects of numerous emerging parameter’s on velocity profile vz and depth of the fluid in the tank are graphically presented. Keywords: Tank drainage, Power law MHD fluid, Analytical solution.

An overview is presented of several diverse branches of work in the area of effectively 2D fluid equilibria which have in common that they are constrained by an infinite number of conservation laws. Broad concepts, and the enormous variety of physical phenomena that can be explored, are highlighted. These span, roughly in order of increasing complexity, Euler flow, nonlinear Rossby waves, 3D axisymmetric flow, shallow water dynamics, and 2D magnetohydrodynamics. The classical field theories describing these systems bear some resemblance to perhaps more familiar fluctuating membrane and continuous spin models, but the fluid physics drives these models into unconventional regimes exhibiting large scale jet and eddy structures. From a dynamical point of view these structures are the end result of various conserved variable forward and inverse cascades. The resulting balance between large scale structure and small scale fluctuations is controlled by the competition between energy and entropy in the system free energy, in turn highly tunable through setting the values of the conserved integrals. Although the statistical mechanical description of such systems is fully self-consistent, with remarkable mathematical structure and diversity of solutions, great care must be taken because the underlying assumptions, especially ergodicity, can be violated or at minimum lead to exceedingly long equilibration times. Generalization of the theory to include weak driving and dissipation (e.g., non-equilibrium statistical mechanics and associated linear response formalism) could provide additional insights, but has yet to be properly explored.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Plastic materials have revolutionized modern life, particularly in the domain of food packaging, owing to their versatility, lightweight nature, and ease of processing. However, the environmental ramifications of non-degradable plastics have raised concerns. Polylactic acid (PLA), derived from renewable sources, presents a sustainable alternative due to its biodegradability and exceptional barrier, mechanical, and safety properties. Nevertheless, the high UV transmittance of PLA limits its use for photosensitive food and pharmaceutical packaging, where UV radiation can lead to nutritional loss and spoilage. Various methods have been explored to enhance the UV-blocking capabilities of PLA, including the integration of inorganic nanoparticles and surface coatings. Despite advancements, these approaches often compromise the inherent transparency of PLA. Incorporating large conjugated groups can maintain transparency but introduces additional challenges. This paper reviews modification methods to enhance PLA's UV-barrier properties and anticipates its expanded utility in food and drug packaging, promoting UV resistance and diversifying PLA's applications.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

The Baltic Sea coast is one of the geographical areas of Europe most threatened by the current climate change. This issue concerns erosional processes, groundwater flows affecting sea-shore settings. Long term hydrological investigations within the western sector of the Łeba Barrier, northern Poland, based on a network of monitoring stations, coupled with the meteorology records of the past 12 years, revealed significant fluctuations in ground water fluxes from the Baltic Sea on the adjoining mainland. Groundwater resources are negatively affected by sea-level drops in the coastal areas along the southern Baltic coast. The low sea levels strengthen the effects of low precipitation and high temperatures, causing altogether the occurrence of hydrogeological drought in the coastal sandbar areas. Drought periods are characterized by lowering of water-tables in the Slowinski National Park. The obtained results have direct relevance to a long-term assessment of water resources, environmental protection of the climatically most susceptible ecosystems, as well as the tourism management of this popular visitors’ destination.

Aging is a major risk factor for Alzheimer's disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood-brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.

Insulin receptors are internalized by endothelial cells; however, the impact of hyperinsulinemia on this process is not known. Thus, the aim of this study is to determine the role of hyperinsulinemia on insulin receptor function and internalization, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). To this end, hippocampal microvessels were isolated from male C57Bl/6J mice on either a control or high-fat diet and assessed for insulin receptor signaling. Cell surface insulin receptors in brain microvascular endothelial cells were labelled with biotin to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without Claramine treatment, a potent PTP1B antagonist. Our results indicated that insulin receptor levels increased in tandem with insulin receptor dysfunction in the high-fat diet mouse hippocampal microvessels. Hyperinsulinemic cell-receptors demonstrate a shift in splice variation towards decreased IR-A/IR-B ratios and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling, however, Claramine restored signaling and receptor internalization in hyperinsulinemic cells. In conclusion, hyperinsulinemia negatively impacts brain microvascular endothelial cell insulin receptor function and internalization, likely through both alternative splicing and increased negative feedback from PTP1B.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

The synergistic efficacy of combined treatment mild heat (MH) and dielectric barrier discharge (DBD) plasma in Bacillus cereus-contaminated red pepper powder was tested. A cocktail of three strains of B. cereus (NCCP 10623, NCCP 14579, ATCC 11778) was inoculated onto red pepper powder and then treated with MH (60 ℃ for 5-20 min) and DBD plasma (5-20 min). Treatment with MH and DBD plasma alone for 5~20 min resulted in reductions of 0.23~1.43 and 0.12~0.96 log CFU/g, respectively. Combined treatment with MH and DBD plasma was the most effective at reducing B. cereus counts on red pepper powder and resulted in log-reductions of ≥ 6.0 log CFU/g. The largest synergistic values (4.24-4.42 log) against B. cereus in red pepper powder were obtained by the combination of 20 min MH and 5~15 min DBD plasma. Hunter color ‘‘L’’, ‘‘a’’, and ‘‘b’’ values of the combination-treated samples were not significantly different from those of non-treated samples. Also, no significant (p > 0.05) differences in pH values between samples were observed. Therefore, these results suggest that the combination of MH treatment and DBD plasma can be potentially utilized in the food industry to effectively inactivate B. cereus without incurring quality deterioration of red pepper powder.

The controls of depositional environments on reservoir quality have been evaluated in terms of porosity and permeability of the Gabo Field, Niger Delta, Nigeria. Data used in this research include Well logs, Core data and photos, and grain size analysis for Wells 51 and 52 in the study area. Standard methods as applicable in petrophysical and sedimentological analysis has been adopted. Thirteen reservoir units have been identified in wells 51 and 52 which had 5 reservoirs cored each. The lithofacies units of the identified reservoirs across the study area, comprise pebbly sands, coarse -, medium -, fine- and very fine-grained sands, sandy mud, silty sands and heteroliths. The heteroliths – very fine-grained silty muds are highly bioturbated. Ophiomorpha and skolithos are the major trace fossils with sedimentary structures (ripple lamination, wavy lenticular and planar beds, cross bedded sands, coarsening and fining upward). The facies associations interpreted for the study area are Channel and Coastal barrier systems and the environment of deposition as distributary channel, upper and lower shoreface. The sedimentary processes that deposited facies ranged from high energy regimes, reworking by waves to low energy with periodic influx of silts and muds. The average porosity and permeability for reservoirs in Well 51 is 16.7% and 1317 Md, reservoirs in Well 52 is 28.2% and 2330Md whereas porosity range for the study area is 2% - 32% and permeability is 1.2 – 10600 Md. The reservoir quality reservoir of the sand units in Well 51 (7, 9 and 13) and Well 52 (5, 7, 9, 11 and 13) is excellent - good, this is because of the dynamics environments of deposition (upper shoreface and distributary channel) as well as the mechanisms that play out during deposition such as bioturbation, sorting, sedimentary structures formed. Whereas the poor quality across the reservoirs especially the lower shoreface and prodelta facies is as result of lack bioturbation, connectivity, multiplicity of burrows that may have been plugged by clay and intercalation of shale and sand (heteroliths). This research has shown that environments of deposition have direct influence the reservoir quality in terms of porosity and permeability.

The scene for regional biogeography and human settlements in Central Amazonia is set by the river network, which presumably consolidated in the Pliocene. However, we present geomorphological and sediment chronological data showing that the river network has been anything but stable. Even during the last 50 kyr, the tributary relationships have repeatedly changed for four major rivers, together corresponding to one third of the discharge of the Amazon. The latest major river capture event converted the Japurá from a tributary of the Rio Negro to a tributary of the Amazon only 1000 years ago. Such broad-scale lability implies that rivers cannot have been as efficient biogeographical dispersal barriers as has generally been assumed, but that their effects on human societies can have been even more profound. Climate change and deforestation scenarios predict increasing water levels during peak floods, which will likely increase the risk of future river avulsions. This may have disastrous consequences for the local human societies, especially in those areas where the current floodplains are at only marginally lower elevations than the nearest water divide. We suggest that the prevailing paradigm of rivers as principal structuring elements of Amazonian biogeography needs to be re-evaluated, and that land use planning and civil risk assessment should take the possibility of river avulsions into account.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

Introduction: Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Materials and methods: Fetal biometric data, and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Results: Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β=0.39, p

Sweat rate and electrolyte losses have a large inter-individual variability, a personalized approach to hydration can overcome this issue to meet an individual’s needs. This study aimed to investigate the effects of personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with 3-day of familiarization exercise following by two random exercise trials with a either PHS or control (CON). Then, participants crossed-over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, and HYP+CON. The PHS was prescribed according to participants’ fluid and sweat sodium losses. CON drank ad-libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: 1) 45min constant workload; 2) high-intensity intermittent exercise (HIIT) until exhaustion. PHS had a significantly greater fluid intake compared to CON. HYP+CON produced the lowest sweat sodium concentration. HYP+PHS had a lower thirst perception and a longer HIIT compared to HYP+CON. Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor to preventing negative physiological consequences during high-intensity exercise in the heat.

This work is aimed at investigating the capabilities and limits of the mid-fidelity numerical solver DUST for the evaluation of wind turbines aerodynamic performance. In particular, this study was conducted by analysing the benchmarks NREL- 5MW and Phase VI wind turbines, widely investigated in literature by from experimental and numerical activities. The work started by simulating simpler configuration of the NREL- 5MW turbine to progressively integrate complexities such as shaft tilt, cone effects and yawed inflow conditions, offering a detailed portrayal of their collective impact on turbine performance. A particular focus was then given to the evaluation of aerodynamic responses from the tower and nacelle, as well as aerodynamic behavior in yawed inflow condition, crucial for optimizing farm layouts. In the second phase, the work was focused on NREL Phase VI turbine due to the availability of experimental data on this benchmark case. Comparison of DUST simulations results with both experimental data and high-fidelity CFD tools shows the robustness and adaptability of this mid-fidelity solver for this applications, thus opening a new scenario for the use of such mid-fidelity tools for the preliminary design of novel wind turbines configurations or complex environments as wind farms, characterised by robust interactional aerodynamics.

In this paper is proposed an analytical technique which can be used to obtain the forced response of a cantilevered tube conveying fluid. Considering the pipe subjected to an arbitrary harmonic force either distributed or concentrated, an analytical solution is found using Green’s function method. The solution obtained of the closed form satisfies the differential equations in a classical sense. The presented method giving the exact solutions is more precise than the classical eigenfunction expansion or Galerkin’s method with no need to the eigenfunctions or eigenvalues.

In this study, nano-diamond (ND) and MoS2 powder are used as additives in a carbonyl iron based magnetorheological fluid (MRF) to improve its tribological performance. MRFs are prepared by dispersing 35 wt.% of CI particles in silicone oil, and adding different proportions (0, 1, 3 or 5 wt.%) of ND and MoS2 additives. Seven kinds of MRFs are made and tested using reciprocating friction and wear tester under different normal loads, and then the friction characteristics are evaluated through analyzing experiment results. The morphology properties of MRFs and contacting surfaces before and after tests are also observed using a scanning electron microscope and analyzed by energy-dispersive X-ray spectroscopy. The results show that the appropriate weight percentage of MoS2 additives may decrease friction coefficient and wear zone. It is also demonstrated from the detailed analyses of worn surfaces that the wear mechanism is influenced not only by additives but also by applied normal load and magnetic field strength.

Heat dissipation from Li-ion batteries is a potential safety issue for large-scale energy storage applications. Maintaining low and uniform temperature distribution, and low energy consumption of the battery storage is very important. We studied the fluid dynamics and heat transfer phenomena of a single cell, 16-cell modules, battery packs, and cabinet through computer simulations and experimental measurements. The results show that the temperature distribution of single cell is relatively uniform when the cell is facing the air flow. In a module, very high air flow rate and large gap between the cells can reduce the cell temperature. A pack with a good thermally conductive case is very important to ensure good heat dissipation of the battery module. Due to limited space in the cabinet, additional air inlets and outlets can be opened outside of the cabinet to slightly lower the pack temperature. Installing fins outside the cabinet can also slightly reduce the temperature inside the cabinet. Liquid cooling medium, such as water, is much better than the air-cooling medium.

Cambodian spices Amomum kravanh, Citrus hystrix and Piper nigrum 'Kampot' have long history of seasoning of food products. In this study, essential oils (EOs) and supercritical CO2 extracts from all three species have been analyzed using GC-MS with two columns of different polarity, whereas EO and CO2 extract from P. nigrum fruits and CO2 extract from the peel of C. hystrix have been isolated and analyzed for the first time. The results showed that A. kravanh EO contained mostly eucalyptol (78.8/ 72.6 %), while CO2 extract was rich in oleic acid (29.26 %) and tricosane (14.74 %). C. hystrix EO was rich in β-pinene (29.95/29.45 %), followed by D-limonene (24.54/23.24 %) and sabinene (9.94/10.23 %). β-pinene (30.2/28.9 %), D-limonene (23.99/23.74 %) and sabinene (13.36/19.55 %) were also predominant in the CO2 extracts. β-Caryophyllene was the main constituent of both EO and CO2 extract from P. nigrum 'Kampot' with contents ranging from 37.84 to 55.84 %, followed by 3-carene (from 7.18 to 18.72 %). Such findings suggest that supercritical CO2 can potentially be used for extraction of all three Cambodian spices. Nevertheless, further research determining the most efficient extraction parameters will be needed before its application in the spice processing practice.

This research, which focuses on wave energy generating technology, suggests a brand-new oscillating float-type wave energy conversion system that is appropriate for the offshore wave environment. To accurately model the device, a three-dimensional viscous numerical pool is created based on STAR-CCM+. The array-type power generation device is numerically simulated using theoretical analysis and numerical simulation, and the wave energy power generation device is arranged as double floats in the front and rear rows, representing triangular array type and rectangular array type, respectively. The triangular array type is a superior layout and can make greater use of marine resources, according to this paper's analysis of the hydrodynamic and power generation impacts of the three array types. The findings are meant to serve as a guide for engineering practice.

The development of cost-effective methods for estimating hydraulic conductivity profiles has been an ongoing effort in the field of engineering practice, which can be used to increase availability to clarify the hydrogeological complexity of fractured rock aquifers for the aid of solving groundwater-related problems. A methodology is presented, which combines electrical well logs, fluid conductivity logs, double packer hydraulic tests, Archie’s law, and the Kozeny-Carman-Bear equation to investigate relations between formation factor and hydraulic conductivity. This method was applied to develop hydraulic conductivity profiles based on the data collected from 88 boreholes in Taiwan's mountainous areas. The investigation results include: (1) Well logging signals were suggested to be categorized by rock types to establish effective relationships with hydraulic conductivity. (2) Removing the mud-bearing section data with two proposed data clustering techniques could effectively enhance the correlation between the formation factor and hydraulic conductivity. (3) The predictive models for estimating hydraulic conductivity have been developed for sandstone, schist, and slate. (4) The prevalence of clay content in most of Taiwan's mountainous rock formations has been found, which implies that careful consideration of clay-related issues in complex geologic formations is essential while applying Archie's law theory.

Aujeszky Disease Virus (ADV) is a double-stranded DNA virus with a lipoprotein envelope. The natural hosts of the infection are suidae, but the virus can infect many other mammals. The gold-standard method identified by the WOAH for the diagnosis of Aujeszky disease is ELISA method. The objective of this study was to compare the performance of meat juice and oral fluid matrices using a commercial ELISA kit designed for serum. A total of 80 blood and oral fluid samples were collected from four pig farms selected for this study. Diaphragm muscle samples of about 100 g and blood samples were collected from 213 animals at the abattoir. These biological matrices were collected from the same animals and tested using a competitive ELISA kit to detect antibodies against ADV. The relative accuracy of the meat juice compared to that of the serum was 96.7% (95% CI: 93.3%-98.7%), with 206 correct results out of 213. The relative accuracy of the oral fluid compared to that of the serum was 61.3% (95% CI: 49.7%-71.9%), with 58 correct results out of 80. Meat juice has a better combination of sensitivity and specificity than oral fluid. The usage of meat juice in routine diagnostic examinations could be achieved after further investigations to optimize the procedure.

An axial wind turbine's performance is analyzed numerically using geometrical and operational parameters. The performance of an axial wind turbine is simulated using three-dimensional computational fluid dynamics (CFD) and compared with experimental data, which confirms the validity of the assumptions and method used. A study of the effects of air in clean and sand particlesy conditions is then conducted. A study was also conducted on mechanical power and the impact of the blade tip on the extension of the vortex. It has been found that different sand particle sizes have a significant impact on wind performance numerically from 0.1 to 0.9, and the results indicate that mechanical power and thrust increase as wind velocity increases, but larger sand particle sizes reduce power, thrust, and torque as wind velocity increases. The turbulence intensity causes the pressure distribution on the walls to be irregular, thereby increasing mechanical power and propulsion force. Moreover, as the wind velocity increases, the tip speed ratio increases and the vortexes are subsequently extended.

Onion is not just an edible food but its seeds can also be an important source of valuable oil with various sensitive applications mainly in pharmaceutical, cosmetic and food fields. This has encouraged the use of a supercritical fluid extraction in the present study to obtain oil from local onion seeds, hence avoiding even traces of organic solvents. For several advantages carbon dioxide at supercritical conditions was used as the fluid. The effects of four key operating parameters like pressure, temperature, particle size and CO2 mass flowrate were investigated in ranges of [150, 250 bars], [35, 65°C], [0.25, 0.85mm] and [50, 100g/min], respectively, using a Box-Behnken experimental design, for a constant extraction time of 3 hours. This led to optimal operating conditions of 250 bar, 57°C, 0.25mm and 50g CO2/min for the highest oil extraction yield value of 24.36%. Furthermore, gas chromatography-mass spectrometry (GC-MS) was used to identify qualitatively and quantitatively the chemical composition of the onion seed oils. About ten components were identified in the extracts, but with four major ones, namely 9,12-Octadecadienoic acid ,methyl ester, 9,12-Octadecadienoic acid (Z,Z)-,methyl ester, 9-Octadecadienoic acid (Z)-,methyl ester and Hexadecanoic acid, methyl ester, present with significant percentages, depending on the operating parameters values. These fatty acids are well known for their benefits for human health. Finally the study shows the importance and the merits of fluids when used under particular conditions of pressure and temperature, in very sensitive industrial fields.

Idiopathic scoliosis (IS) is an unexplained dysplasia of the spine that can occur at any age, with idiopathic scoliosis making up the largest proportion of the total population worldwide, approximately 2-3%. Scoliosis is not just a cosmetic defect, but the development of the spinal deformity can lead to cardiovascular and respiratory lesions, often resulting in serious health problems. Treatment of the condition usually involves major surgery, which is both a physical and financial burden for patients. In order to clarify the aetiology of IS and provide a theoretical basis for new diagnostic and treatment methods IS, it is important to use different animal models for experiments. Zebrafish is an emerging model animal with a short reproductive cycle, minimal breeding expenses, and other beneficial traits including in vitro fertilisation, in vitro development, and embryo transparency. As a result, genetic alteration and observation are simpler than with traditional model animals. This study examines the history of animal models for IS research, focuses on the benefits and drawbacks of zebrafish as an IS model and the advances it provides to IS research, and anticipates zebrafish application prospects in IS research.

With the development of free trade port in Hainan Island, the construction of tourist roads around the island is also in full swing. Under the weather conditions of strong typhoon and rainstorm in Hainan, the highway cutting slope built on the coastal weak sandy terraces has strong sand loss and is easy to be scour by rainfall. MICP green spray irrigation solidification technology is used to strengthen the sandy cutting, and pore water pressure monitoring is carried out on the slope model during MICP solidification and rainfall scour. Combined with the model pore water pressure and flow slip failure pattern, dynamic analysis was carried out. The results show that MICP sprinkler irrigation technology can solidified the surface of the slope model in a short time, and the cementation depth of the model reaches 4cm after three sets of rotation reinforcement. The surface reinforcement effect is good, and the sand samples are closely connected. Under the erosion effect of simulated rainfall intensity, the sand loss of the slope is weakened, and no sand binding damage occurs, and the integrity is enhanced. Due to the cementation between sand grains, most of the rainfall was converted into runoff, and the slope slid after 150s. When the slope began to slip, the leading edge of the slope model lost sand and unloaded, and the failure mode was graded creep slip failure. Finally, the slope was divided into several blocks due to the continuous expansion of cracks after the slope failure. The erosion stability of the sandy slope under heavy rains is optimized and the sand loss is prevented effectively. In this study, a new method of MICP remediation techniques is proposed, which provides a new test basis for the application of MICP technology in practical engineering.

We previously described spherical crystals in minerals from prismatine-bearing rock from Waldheim, including ultrahigh-pressure (UHP) minerals such as stishovite and coesite, in uncommon crustal environments. To determine if this was an outlier phenomenon, we searched for equivalent inclusions in other rocks, which we indeed discovered in a Variscan tin granite sensu stricto from the Erzgebirge. The identification of more examples of this phenomenon implies a novel, very rapid transcrustal transport mechanism, which however is not unique. We demonstrate the unusual occurrence of UHP minerals (moissanite, diamond, lonsdaleite, stishovite, coesite, kumdykolite, and cristobalite-II) in topaz of granitic rocks, which reflects the direct interaction of mantle and crust via supercritical fluids or extremely volatile-rich melts. Most UHP minerals are tiny inclusions in moissanite. The trapping by this mineral prevents a fast reaction in an extraneous environment.

Road vehicles are a large contributor to Nitrogen Oxides (NOx) pollution. The routine road-side monitoring stations, however, may underrepresent the severity of personal exposure in urban areas, because long-term average readings cannot capture the effects of momentary, high peaks of air pollution. While numerical modelling tools historically have been used to propose an improved distribution of monitoring stations, ultra-high resolution Computational Fluid Dynamics models can further assist the relevant stakeholders in understanding the important details of pollutant dispersion and exposure at local level. This study deploys a 10 cm-resolution CFD model to evaluate actual high peaks of personal exposure to NOx from traffic, by tracking the gases emitted from the tailpipe of moving vehicles being dispersed towards the roadside. The investigation shows that a set of four Euro 5-rated diesel vehicles travelling at constant speed may generate momentary road-side concentrations of NOx as high as 1.25 mg/m3, with 25% expected increase for doubling the number of vehicles and approximately 50% reduction when considering Euro 6-rated vehicles. The paper demonstrates how the numerical tool can be used to identify the impact of measures to reduce personal exposure, such as protective urban furniture, as traffic patterns and environmental conditions change.

Lipid metabolism is clearly associated to Parkinson´s disease (PD). Although lipid homeostasis has been widely studied in multiple animal and cellular models as well as in blood derived from PD individuals, the cerebrospinal fluid (CSF) lipidomic profile in PD remains largely unexplored. In this study, we have characterized the CSF lipidomic imbalance between neurologically intact controls (n=10) and PD subjects (n=20). The combination of dual extraction with ultra-performance liquid chromatography-electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-qToF-MS/MS) allowed to monitor 257 lipid species across all samples. Complementary multivariate and univariate data analysis pointed out that glycerolipids (mono-, di-, and triacylglycerides), saturated and mono/polyunsaturated fatty acids, primary fatty amides, glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines), sphingolipids (ceramides, sphingomyelins), N-acylethanolamines and sterol lipids (cholesteryl esters, steroids) were significantly increased in the CSF of PD compared to control group. These results, despite the limitation of being obtained in a small population, demonstrate and extensive CSF lipid remodelling in PD, shedding new light on the deployment of CSF lipidomics as a promising tool to identify potential lipid markers as well as discriminatory lipid species between PD and other atypical parkinsonisms.

This study addressed a Fluid-Structure Interaction of an open Water test for vp1304 propeller to predict pressure and stress distributions with a low cost and high precision method. The most striking aspect of such a method(one-way coupling) is to use one hydrodynamic solution for the number of different structural sets involved in other materials or different layup methods and combinations of layers. An open-access software(OpenFOAM) with an open-source code solver is used to simulate the fluid domain. Abaqus is used To evaluate and predict the deformation and strength of the blade with the Finite Element Method(FEM). The coupling approach is based on dry condition, which means the added mass effects due to propeller blades vibration is neglected. The pressures imposed on the blades are extracted from the fluid solver for each time step. Then, These pressures role as a load condition for the structure solver. This approach was verified in the last paper(wedge impact); a key factor for the present solution is the rotational rate interrelated between two solution domains, which is explained in this paper. Finally, the blades' stress and strain are calculated and compared in each advance coefficient.

Adhesion systems are very important in robots for infrastructure inspection (especially in vertical walls). They present the challenge of optimizing the ratio vacuum/power consumption in battery-powered robots. In this paper a CFD (Computer Fluid Dynamics) modelling and optimization process of a robot adhesion system is carried out to determine the best performing configuration in terms of vacuum and power consumption. Analytical and numerical models were developed to predict the behaviour of the system for different configurations. The models were validated, using test rig measurements, by calibrating an arbitrary defined inlet height that simulates the leakage flow. Then, different geometric parameters were varied to determine the best performing configuration based on the vacuum/power consumption ratio value. The model presented in the paper was capable of predicting the behaviour of the system for different configurations, with a margin of error of 15% for the vacuum prediction and a 25% for the motor power calculation. Finally, the model was used to optimize parameters of the system, like the number of blades of the impeller. The adhesion system was conceived for the modular autonomous climbing legged robot ROMERIN.

It is a theoretical exportation for mass transpiration and thermal transpiration of Casson nanofluid over an extending cylindrical surface. The Stagnation point flow through porous matrix is influenced by magnetic field of form strength. Appropriate similarity functions are availed to yield the transmuted system of leading differential equations. Existence for the solution of momentum equation is proved for various values of Casson parameter β, magnetic parameter M, porosity parameter Kp and Raynolds number Re in two situations of mass transpiration (suction/injuction). Moreover, uniqueness results are discussed and for skin friction factor are established to attain accuracy for large injection values. Thermal and concentration profiles are delineated numerically by applying Runge-Kutta method and shooting technique.

The adoption of Machine Learning (ML) for building emulators for complex physical processes has seen an exponential rise in the recent years. While neural networks are good function approximators, optimizing the hyper-parameters of the network to reach a global minimum is not trivial, and often needs human knowl- edge and expertise. In this light, automatic ML or autoML methods have gained large interest as they automate the process of network hyper-parameter tuning. In addition, Neural Architecture Search (NAS) has shown promising outcomes for improving model performance. While autoML methods have grown in popularity for image, text and other applications, their effectiveness for high-dimensional, complex scientific datasets remains to be investigated. In this work, a data driven emulator for turbulence closure terms in the context of Large Eddy Simulation (LES) models is trained using Artificial Neural Networks and an autoML frame- work based on Bayesian Optimization, incorporating priors to jointly optimize the hyper-parameters as well as conduct a full neural network architecture search to converge to a global minima, is proposed. Additionally, we compare the effect of using different network weight initializations and optimizers such as ADAM, SGDM and RMSProp, to explore the best performing setting. Weight and function space similarities during the optimization trajectory are investigated, and critical differences in the learning process evolution are noted and compared to theory. We observe ADAM optimizer and Glorot initialization consistently performs better, while RMSProp outperforms SGDM as the latter appears to have been stuck at a local minima. Therefore, this autoML BayesOpt framework provides a means to choose the best hyper-parameter settings for a given dataset.

Persistent, non-explosive passive degassing is a common characteristic of active volcanoes. Distinct periodic components in measurable parameters of gas release have been widely identified over timescales ranging from seconds to months. The development and implementation of high temporal resolution gas measurement techniques now enables the robust quantification of high frequency processes operating on timescales comparable to those detectable in geophysical datasets. This review presents an overview of the current state of understanding regarding periodic volcanic degassing, and evaluates the methods available for detecting periodicity, e.g., autocorrelation, variations of the Fast Fourier Transform (FFT), and the continuous wavelet transform (CWT). Periodicities in volcanic degassing from published studies are summarised and statistically analysed, together with analyses of literature-derived datasets where periodicity had not previously been investigated. Finally, an overview of current knowledge on drivers of periodicity is presented and discussed in the framework of four main generating categories, including: (1) non-volcanic (e.g., atmospheric or tidally generated); (2) gas-driven, shallow conduit processes; (3) magma movement, intermediate to shallow storage zone; and (4) deep magmatic processes.

Due to poor ventilation conditions in the tunnel, if gas pipeline leaks, the consequence of the accident will be more serious. Therefore, before the emergency repair, gas in the tunnel needs to be excharged so as not to explode during the repair process. Therefore, it is necessary to study the ventilation of gas in the tunnel. Based on the computational fluid dynamics (CFD) theory and taking the Yanyingshan tunnel section of China-Myanmar pipeline as an example, this paper uses Fluent software to establish the leakage model of the gas pipeline and fan model in the tunnel and analyzes the influence of different fan locations and number of fans on gas concentration. It can be concluded that: (1) the use of press-in method makes it more efficient to discharge gas out of the tunnel. (2) In order to make ventilation efficient, the fan should be arranged in a higher position and needs to be at a distance from the top of the tunnel. (3) Parallel use of two fans has better ventilation effect than single fan.

Starting with a hypothetical geostrophic zonal current in an unbounded ocean, the investigation points out the response of this simple system to a thermal forcing, applied to the free surface and consistent with the maintenance of the geostrophic balance. The main result is the formation of a meridional component of the current, according to the Sverdrup relation, such that the full velocity vector rotates clockwise for heating and anticlockwise for cooling to adjust eventually in the initial zonal direction for large depths.

This article discusses the results of fluid inclusions study in barite collected at the Jan Mayen vent field area (Troll Wall and Perle &amp; Bruce) and Loki’s Castle vent field of the Mohns Ridge segment of the Arctic Mid-Ocean Ridge. Three mafic-hosted volcanogenic massive sulfide deposits were examined within the active vent fields that adequately correspond to geological settings of ultraslow-spreading ridges and PT-conditions. Hydrothermal sediments were investigated to determine the temperature and salinity of the fluids responsible for barite precipitation. The hydrothermal origin of the barite was confirmed by its morphology. Fluid inclusions are two-phase and homogenized into the liquid phase on heating at temperatures below 287ºC. The salt concentration in fluids trapped in inclusions is 2.6–4.4 wt.% NaCl eq. The crystallization temperatures varied from 276ºС to 119ºС and from 307ºС to 223ºС for the Jan Mayen and Loki’s Castle vent fields, respectively. The data obtained allowed us to confirm evidence of fluid phase separation in the hydrothermal systems and to expand our knowledge of the temperature and salinity of mineral fluids previously known from recent direct measurements during the cruises within the G.O. Sars research vessel. The fluid inclusions data obtained from barites emphasize the fluid features characteristic of volcanogenic massive sulfide deposits, the similarities and differences for the studied hydrothermal sites, and allow comparisons with similar products from other active hydrothermal systems.

The growing adoption of distributed energy production technologies, and the potential of energy underutilization when it is produced by non-connected groups, has raised interest in ‘sharing economy’ concepts in the electricity sector. We suggest that mechanisms, such as peer-to-peer (P2P) energy trading, will allow users to exchange their surplus energy for mutual benefits, stimulate the adoption of renewable energy, encourage communities to ‘democratically’ control their own energy supplies for local development, and improved energy efficiency, and create many other benefits This approach is receiving increasing attention across the world, particularly in Germany, the Netherlands and Australia. Nevertheless, the actual development and implementation of these platforms is slow and mostly limited to trial activities. This study investigates the challenges and barriers facing P2P energy trading developments based on previous academic and industry studies. We provide a comprehensive multidimensional barrier analysis through a PESTLE approach to assess the barriers from a variety of perspectives, including the political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) aspects. This approach clarifies the many intersecting problem fields of P2P trading in renewable energy, and the paper identifies a list of such barriers, and discusses the prospects for addressing these issues. We also elaborate on the importance of incentive-based P2P market design.

Reproductive isolating barriers are a crucial element in the speciation process. There are various types of barriers, and within those that act early in the speciation process, the behavioral one can play an important role in isolating populations or closely related species. It has been shown that the high diversity of some taxa correlates with the variation of sexual signals, which facilitate isolation. Here it is explored whether chemical signals may contribute to the high diversity of Liolaemus lizards, which has more than 290 species. Population chemical discrimination was investigated in two co-distributed species, L. tenuis and L. lemniscatus. The studied populations were closely located and likely belonged to the same genetic lineages. Lizards of both species discriminated between scents of their own and different populations, and in most cases, scents from their population were preferred. Results suggest a fast evolution of scents, and their recognition, and there for the ethological barriers associated with the chemical modality may evolve fast. However, because the studied species differed in the strength of the exhibited population chemical discrimination, ethological barriers evolve at different rates across species. It can be concluded that ethological barriers involving the chemical modality may disrupt species' cohesion, contributing to Liolaemus diversification, in synergy or not with geographical barriers.

Purpose: Inducible Slc4a11 KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH3-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study is to investigate the link between oxidative stress and failure of pump and barrier functions and test different approaches to revert the process. Methods: Mice homozygous for Slc4a11 Flox and Estrogen receptor –Cre Recombinase fusion protein alleles at 8 weeks of age were fed Tamoxifen (Tm) enriched chow (0.4 g/Kg) for 2 weeks, and controls were fed normal chow. During the initial 14 days, Slc4a11 expression, corneal thickness (CT), stromal [lactate], Na+-K+ ATPase activity, mitochondrial superoxide levels, expression of lactate transporters, and activity of key kinases were assessed. In addition, barrier function was assessed by fluorescein permeability, ZO-1 tight junction integrity, and cortical cytoskeleton F-actin morphology. Results: Tm induced a rapid decay in Slc4a11 expression that was 84% complete at 7 days and 96% at 14 days of treatment. Superoxide levels increased significantly by day 7; CT and fluorescein permeability by day 14. Tight junction ZO-1 distribution and cortical cytoskeleton were disrupted at day 14 concomitant with decreased expression of Cldn1 yet an increase in tyrosine phosphorylation. Stromal lactate increased by 60%, Na+-K+ATPase activity decreased by 40%, and expression of lactate transporters MCT2 and MCT4 significantly decreased, but MCT1 was unchanged at 14 days. Src kinase was activated but not Rock, PKCα, JNK, or P38Mapk. Mitochondrial antioxidant Visomitin (SkQ1, mitochondrial targeted antioxidant) or Src kinase inhibitor eCF506 significantly slowed the increase in CT, with concomitant decreased stromal lactate retention, improved barrier function, reduced Src activation and Cldn1 phosphorylation, and rescued MCT2 and MCT4 expression. Conclusions: Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that results in perturbation of pump components and barrier function of the CE.

Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). In murine models, chronic SF can impair endothelial function and induce cognitive declines. These deficits are likely mediated, at least in part, by alterations in Blood-Brain Barrier (BBB) integrity. Male C57Bl/6J mice were randomly assigned to SF or sleep control (SC) conditions for 4 or 9 weeks, and in a subset 2 or 6 weeks of normal sleep recovery. Presence of inflammation and microglia activation were evaluated. Explicit memory function was assessed with the novel object recognition (NOR) test, while BBB permeability was determined by systemic dextran-4kDA-FITC injection and Claudin 5 expression. SF exposures resulted in decreased NOR performance and in increased inflammatory markers and microglial activation as well as enhanced BBB permeability. Explicit memory and BBB permeability were significantly associated. BBB permeability remained elevated after 2 weeks of sleep recovery (p<0.01) and returned to baseline values only after 6 weeks. Chronic SF exposures mimicking the fragmentation of sleep that characterizes patient with OSA elicits evidence of inflammation in brain regions and explicit memory impairments in mice. Similarly, SF is also associated with increased BBB permeability, the magnitude of which is closely associated with cognitive functional losses. Despite normalization of sleep patterns, BBB functional recovery is a protracted process that merits further investigation.

In kidney, epithelial barrier has diverse functions in body fluid and electrolyte homeostasis, and urine production. Maintaining epithelial integrity fundamentally builds up physiological functionality of the renal epithelial barrier (REB). Specially, the REB) states regularly in osmotic dynamics. The osmotic dynamics gives rise of osmotic pressure that is a physical force. Overloading of osmotic pressure can crack epithelial integrity and damage REB. How REB endures the osmotic pressure force yet remains enigmatic. LMO7 (LIM domain only 7) is a protein associated with cell-cell junctional complex and cortical F-actin. LMO7 upregulation was observed in cells cultured in hypertonic condition. In kidney, LMO7 predominantly distributes in epithelial cells in renal tubules. Hypertonic stimulation leads to assembly of LMO7 and F-actin in cortical stress fibers in renal epithelial cells. Hypertonic-isotonic alternation as pressure force pushing plasma membrane inward/outward was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. Along with junctional integrity, LMO7 depleted cells resulted in loss of junctional integrity in the epithelial sheet cultured hypertonic medium or hypertonic-isotonic alternation. On the other hand, FAK inhibited by PF-573228 leads to failure in robust cortical F-actin assembly and association of LMO7 with cortical F-actin in epithelial cells responding upon hypertonic stress. Epithelial integrity in context of osmotic stress, LMO7 and FAK signaling both involves in assembling robust cortical F-actin and maintaining junctional integrity. The LMO7 elaborately manages FAK activation in renal epithelial cells, which was evidently demonstrated in NRK-52E cells who have excessive FAK activation and lost epithelial integrity when cells with LMO7 depletion exposed to hypertonic environment. Our data suggests that LOM7 manages FAK activation and is responsible for maintaining REB under osmotic disturbance.

The electrical performance of the back-channel etched Indium–Gallium–Zinc–Oxide (IGZO) thin-film transistors (TFTs) with copper (Cu) source and drain (S/D) which are patterned by a selective etchant was investigated. The Cu S/D were fabricated on molybdenum (Mo) layer to prevent the Cu diffusion to the active layer (IGZO). We deposited the Cu layer using thermal evaporation and performed the selective wet etching of Cu using non-acidic special etchant without damaging the IGZO active layer. We fabricated the IGZO TFTs and compare the performance in terms of linear and saturation region mobility, threshold voltage and ON current (ION). The IGZO TFTs with Mo/Cu S/D exhibits good electrical properties as the linear region mobility is 12.3 cm2/V-s, saturation region mobility is 11 cm2/V-s, threshold voltage is 1.2 V and ION is 3.16 x 10-6 A. We patterned all the layers by photolithography process. Finally, we introduced SiO2-ESL layer to protect the device from the external influence. The results show that the prevention of Cu and introduced ESL layer enhances the electrical properties of IGZO TFTs.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

Focal cerebral ischemia can lead to blood-brain barrier (BBB) breakdown, which is implicated in neuroinflammation and elevation of matrix metalloproteinases (MMPs). The role of the anti-inflammatory protein, monocyte chemotactic protein–induced protein 1 (MCPIP1) plays in the injury of BBB in stroke has not yet been reported. This study was conducted to identify and characterize the role MCPIP1 plays in BBB breakdown. Transient middle cerebral artery occlusion (MCAO) is induced in both wild-type and Mcpip1^-/- mice for 2 hours of occlusion periods followed by reperfusion for 24 or 48 hours. BBB permeability was measured by FITC-dextran extravasation, MMP-9/3 expression was analyzed by western blot, and claudin-5 and zonula occludens-1 (ZO-1) were analyzed by immunohistochemistry and western blot. After MCAO in wild type mouse is induced, there is significantly increase in MCPIP1 mRNA and protein levels. Absence of MCPIP1 leaded to significant increase in FITC-dextran leakage in peri-infarct brain, significant upregulation of MMP-9, MMP-3 and reduced levels of tight junction components, claudin-5 and ZO-1 in the brain after MCAO. Our data demonstrate that absence of MCPIP1 exacerbates ischemia-induced blood-brain barrier disruption by enhancing the expression of matrix metalloproteinases and degradation of tight junction proteins. Overall data indicate that MCPIP1 is important protective role against BBB disruption in cerebral ischemia.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

Geological disposal facilities for radioactive waste pose significant challenges for robust monitoring of environmental conditions within the engineered barriers that surround the waste canister. Temperatures are elevated, due to the presence of heat generating waste, relative humidity varies from 20% to 100%, and swelling pressures within the bentonite barrier can typically be 2-10 MPa. Here, we test the robustness of a bespoke design MEMS sensor-based monitoring system, which we encapsulate in polyurethane resin. We place the sensor within an oedometer cell and show that despite a rise in swelling pressure to 2 MPa, our relative humidity (RH) measurements are unaffected. We then test the sensing system against a traditional RH sensor, using saturated bentonite with a range of RH values between 50% and 100%. Measurements differ, on average, by 2.87% RH, and are particularly far apart for values of RH greater than 98%. However, bespoke calibration of the MEMS sensing system using saturated solutions of known RH, reduces the measurement difference to an average of 1.97% RH, greatly increasing the accuracy for RH values close to 100%.

We propose the Hamiltonian formalism of Bianchi type 1 cosmological model for perfect fluid. We have considered both the equation of state parameter ω and the cosmological constant Λ as the function of volume V(t) which is defined by the product of three scale factors of the Bianchi type 1 line element. We propose a Lagrangian for the anisotropic Bianchi type-1 model in view of a variable mass moving in a variable potential . We can decompose the anisotropic expansion in terms of expansion and shearing motion by Lagrangian mechanism. We have considered a canonical transformation from expanding scale factor to scalar field ø which helps us to give the proper classical definition of that scalar field in terms of scale factors of the mentioned model. This definition helps us to explain the cosmological inflation. We have used large anisotropy(as in the cases of Bianchi models) and proved that cosmic inflation is not possible in such large anisotropy. Therefore we can conclude that the extent of anisotropy is less in case of our universe. Otherwise the inflation theory which explained the limitations of Big Bang cannot be resolved.Part II is contained with some analysis of the lagrangian ; derived in Part I ; on the quintessence model.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from the Terminalia arjuna (Combreatceae) bark, i.e. arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid, and arjunetin, is presented. The studies are based on the in silico pharmacokinetic and biomimetic studies, the acetylcholinesterase (AChE) inhibitory activity tests, and the molecular docking research. Based on the calculated pharmacokinetic parameters, arjunetin and arjunglucoside I are indicated as able to cross the blood-brain barrier. The compounds of interest exhibit marked acetylcholinesterase inhibitory potential, which was tested in the TLC bioautography test. The longest time to reach brain equilibrium is observed for both the arjunic and arjunolic acids and the shortest one for arjunetin. All compounds exhibit high and relatively similar magnitude of binding energies, varying from ca. -15 to -13 kcal/mol. The superposition of the most favorable positions of all ligands interacting with AChE is analyzed. The correlation between the experimentally determined IC50 values and the steric parameters of the molecules is investigated. The inhibition of the enzyme by the analyzed compounds shows their potential to be used as cognition enhancing agents. For the most potent compound (arjunglucoside I; ARG), the kinetics of AChE inhibition is tested. The Michaelis–Menten constant (Km) for the hydrolysis of the acetylthiocholine iodide substrate was calculated to be 0.011 mM.

With the increment of the aging population in recent years, neurodegenerative diseases exert a major global disease burden, essentially as a result of the lack of treatments that can stop the disease progression. Alzheimer’s Disease (AD) is an example of a neurodegenerative disease, that affects millions of people globally, with no effective treatment. Natural compounds have emerged as a viable therapy to fill a huge gap in AD management, and in recent years, mostly fuelled by the Covid-19 pandemic, RNA-based therapeutics have become a hot topic in the treatment of several diseases. Treatments of neurodegenerative diseases face significant limitations due to the complex and interconnected pathways that lead to their hallmarks and, also due to the necessity to cross the blood–brain barrier. Nanotechnology has contributed to surpass this bottleneck in the treatment of AD, by promoting safe and enhanced drug delivery to the brain. In particular, exosome-like nanoparticles, a hybrid delivery system combining exosomes and liposomes' advantageous features, are demonstrating great potential in the treatment of central nervous system diseases.

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

The idea of using the lytic power of viruses against the malignant cells has been entertained for many decades. However, oncolytic viruses (OV) gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of the oncolytic herpesvirus to treat advanced melanoma. OVs offer an attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, yet the latter effect is less well studied. Nevertheless, OVs can be envisaged as potential in situ tumor vaccines. The therapeutic potential of OVs can be instigated further by using the molecular biological and biotechnological tools to modify the existing viruses for their optimal tumor selectivity and enhanced immune stimulation. Furthermore, OVs can be readily combined with other therapeutic agents to increase the efficacy of the existing therapeutic schemes. In this review, we discuss biotechnological advances in the development of therapeutic applications of OVs in Russia. Particular emphasis is made on the OV-mediated treatment of glioblastoma. In addition, we highlight the challenges of oncolytic virotherapy, and describe the strategies to optimize current approaches to improve clinical outcomes.

Lead-acid batteries utilised in electrical substations release hydrogen and oxygen when these are charged. These gases could be dangerous and cause a risk of fire if they are not properly ventilated. Therefore, this research seeks to design and implement a network control panel for heating, ventilation, and air-conditioning systems (HVACS). This is done using a specific range of controllers, which have more than thirty loops of proportional, integral and derivative (PID) control to achieve a cost-effective design. It performs the required function of extracting hydrogen, oxygen, and maintaining the desired temperature of the battery storage room within the recommended limits (i.e. 25°C ±1°C tolerance) without compromising quality as set out in the user requirement specification in Appendix-A. The system control panel allows the user to access control parameters such as changing temperature set-points, fan-speed, sensor database amongst others. The hardware is configured to detect extreme hydrogen and oxygen gas content in the battery room and ensure that the HVACS extract the gas content to the outside environment. The results of the system show that the network control panel effectively operates as per the recommended system requirements. Therefore, the effective operation of the HVACS ensures sufficient gas ventilation, thus mitigating the risk of fire in a typical battery storage room. Furthermore, the effective operation of HVACS enhances battery lifespan because of regulated operating temperature, which is conducive to minimise the effect of sulfation in lead acid Batteries (LABs).

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

In our previous study, a novel barrier processing on a porous low-dielectric constant (low-k) film was developed: an ultrathin Mn oxide on a nitrogen-stuffed porous carbon-doped organosilica film (p-SiOCH(N)) as a barrier of the Cu film was fabricated. To form a better barrier Mn₂O_3-xN film, an additional annealing at 450°C was implemented. In this study, the electrical characteristics and reliability of this integrated Cu/Mn₂O_3-xN/p-SiOCH(N)/Si structure is investigated. The proposed Cu/Mn₂O_3-xN/p-SiOCH(N)/Si capacitors exhibited poor dielectric breakdown characteristics in the as-fabricted stage, although, less degradation was found after thermal stress. Moreover, its time-dependence-dielectric-breakdown electric-field acceleration factor slightly increased after thermal stress, leading to a larger dielectric lifetime in a low electric-field as compared to other MIS capacitors. Furthermore, its Cu barrier ability under electrical or thermal stress was improved. As a consequent, the proposed Cu/Mn₂O_3-xN/p-SiCOH(N) scheme is a promising integrity for back-end-of-line interconnects.

Using co-precipitation to synthesize (CeO2)0.95(Y2O3)0.05 (YDC) and solid reaction method to synthesize (CeO2)0.75(ZrO2)0.25 (ZDC), and the characterization for both crystal structure and micro-structure of the two materials was conducted with X-ray diffraction (XRD) and scanning electron microscope (SEM) methods. Prepare the YDC and ZDC based limited current O2 sensor by employing platinum pasting bonding method. Sensing characteristics of the sensor were obtained at different conditions and study on the impact of temperature, O2 concentration as well as water vapor pressure on the sensing characteristics had been conducted. XRD results show that the phase structure of both YDC and ZDC is cubic phase. SEM results show that both YDC and ZDC layers are dense layers, which are then qualified to be the composition materials of the sensor. This limited current O2 sensor shows good sensing performance and conforms to the Knudsen model. Log(IL•T) depends linearly on 1000/T with R2 of 0.9904, IL depends linearly on x(O2) with R2 of 0.9726 and sensing characteristics are not affected by p(H2O).

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species. The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

Hemodynamic relevance of differently located stenoses of the internal jugular veins remains undetermined. It particularly concerns nozzle-like strictures in the upper parts of these veins and stenotic jugular valves located at the end of this vein. This study was aimed at understanding flow disturbances caused by such stenoses. Computational fluid dynamics software, Flowsquare+, was used. We constructed 3-dimensional models of venous outflow, comprising two alternative routes: tube representing the internal jugular vein and irregular network representing the vertebral veins. At the beginning of the tube representing the internal jugular vein, differently-shaped and sized short strictures, representing nozzle-like strictures were built in. At the end of this tube, differently-shaped membranes, representing the jugular valve, were built in. With the use of computational fluid dynamics modeling, we studied how these two obstacles influenced the outflow. We found that the most relevant outflow disturbances were evoked by nozzle-like strictures in the upper part of the internal jugular vein that were either small, long or asymmetrically positioned. Very tight stenotic valves and septum-like malformed valve were equally hemodynamically relevant. These findings suggest that both upper and lower strictures of the internal jugular vein can be of clinical significance.

The emergence of electric vehicles has brought new issues such as the problem of rolling element bearings (REBs) operating at high speeds. Losses due to these components in mechanical transmissions are a key issue and must therefore be taken into account right from the design stage of these systems. Among these losses, the one induced by the motion of rolling elements , known as drag loss, becomes predominant in high-speed REBs. Although an experimental approach is still possible, it is difficult to isolate this loss in order to study it properly. A numerical approach based on CFD is therefore a possible way forward, even if other issues arise. The aim of this article is to study the ability of such an approach to correctly estimate the drag coefficient associated with the motion of rolling elements. The influence of the numerical domain extension, the mesh refinement, the simplification of the ring shape and the presence of the cage, on the values of the drag coefficient is presented. While it seems possible to compromise on the calculation domain and mesh size, it appears that the other parameters must be taken into account as much as possible to obtain realistic results.

: AliCPT-1 is the first Cosmic Microwave Background (CMB) experiment in China, dedicated to achieve accurate measurements of B-mode polarization. Situated in Ali of Tibet, China, this telescope is currently undergoing deployment and will operate in two frequency bands centered at 90 and 150 GHz. The Far-Field Flat Mirror（FFF）is a calibration device of AliCPT-1 telescope for far-field beam mapping. The design of FFF is optimized for easy assembly and adjustment. Meteorological station data reveals that the maximum wind speed near FFF is 17.5 m/s, while the maximum wind speed on the windward side is 8 m/s. The wind pressure on FFF was analysed using a maximum wind speed of 17.5m/s as the input condition, based on the fluid-structure coupling method in ANSYS. The results demonstrate that it is safe and reliable when withstanding combined gravity and wind pressure loads. The torque on the mount is within the motor rated torque. The flatness of the FFF reflective surface can be adjusted to an RMS value of 0.05 mm when taken into account the effect of gravity and assembly accuracy. The deformation caused by the maximum wind loads is approximately 0.0587 mm under the protection of wind-proof wall. The combined deformation is 0.077 mm in RMS value combining the two influences, which is less than 1/20 of wavelength. The FFF mirror assembly is stable and precisely for telescope calibration.

Hydrocephalus is caused by an overproduction of cerebrospinal fluid (CSF), a blockage of fluid circulation, or improper reabsorption. CSF accumulation in the brain’s ventricles causes ventriculomegaly and brain cell damage. Hydrocephalus can be caused by brain trauma, hemorrhage, infection, tumors, or genetic mutations. Currently, there is no cure for hydrocephalus. Treatments like shunting and endoscopic third ventriculostomies are used, but unfortunately, these techniques require brain surgery and have high failure rates. To advance the development of hydrocephalus treatments, physiologically relevant pre-clinical models are crucial. This review covers some of the current animal and cell culture methods used to study hydrocephalus. The choroid plexus epithelium (CPe) is thought to be the major producer of CSF in the brain. It is a polarized epithelium that regulates ion and water movement from a fenestrated capillary exudate to the ventricles. Despite decades of research, control of electrolyte movement in the CPe is still not fully understood. This review discusses important transporters on the CPe and how some of these could be potential targets for hydrocephalus treatment.

In view of the inability to directly and accurately obtain the athlete's aerodynamic force during take-off phase through wind tunnel test, the athlete's aerodynamic force and surrounding flow field form under different take-off postures are obtained through numerical simulation research, and the effects of different take-off modes on the aerodynamic characteristics during take-off in ski jumping are discussed. The multi-body system composed of the athlete and skis was selected as the research objects. By using partially averaged Navier-Stokes (PANS) turbulence model and 3D numerical simulation of computational fluid dynamics (CFD), the aerodynamic characteristics of the athlete under different take-off postures were predicted. Take-off modes include knee-push-hip (KPH) mode and hip-drive-knee (HDK) mode, and the hip joint angle of HDK mode is significantly greater than KPH mode. First, the aerodynamic force ratio of the athlete’s torso and legs is obviously large. Although the aerodynamic force of arms themselves is not obvious, they have a great impact on the overall aerodynamic characteristics of the athlete, so the posture of arms cannot be ignored. Then, the total drag and moment of HDK mode are significantly higher than that of KPH mode, and the lift-to-drag ratio of HDK mode is significantly lower than that of KPH mode. At first the total lift of HDK mode is higher than that of KPH mode, but in the last attitude the total lift of HDK mode does not rise but fall, and finally the total lift of HDK mode is lower than KPH mode. The aerodynamic characteristics change dramatically during take-off phase, and the aerodynamic characteristics of the two take-off modes are quite different, and these changes and differences are difficult to be observed in real training and competition site. KPH mode has obvious aerodynamic advantage over HDK mode. During the take-off process, the athlete should increasethe force generated by the knee joint extension and appropriately reduce the speed of hip joint extension, and control the using force order of the lower limb joints, and push hip joint extension by knee joint extension, in order to avoid issues such as the hip joint angle is too large, the hip joint extension angle is too fast, the center of gravity is to back and other problems. Studying the aerodynamic characteristics during the take-off phase provides valuable insights for athletes to achieve favorable flight postures after take-off, offering scientific guidance to improve training strategies and enhance competitive performance.

Machine learning (ML) based on neural network (NN) facilitates data-driven techniques for handling large amounts of data, either obtained through experiments or simulations at multiple spatio-temporal scales, thereby finding the hidden patterns underlying these data and promoting efficient research methods. The main purpose of this paper is to extend the capabilities of a new solver, called realFluidReactingNNFoam, under development at University of Perugia in OpenFOAM with NN algorithm for replacing complex real-fluid thermophysical property evaluations, using the approach of coupling OpenFOAM and Python-trained NN models. Currently, NN models are trained against data generated using the Peng-Robinson equation of state (PR-EoS) assuming mixture frozen temperature. The OpenFOAM solver, where needed, calls the NN models in each grid-cell with appropriate inputs, and the returned results are used and stored in suitable OpenFOAM data structures. Such inference for the thermophysical properties is achieved via the “Neural Network Inference in C made Easy” (NNICE) library, which proved to be very efficient and robust. The overall model is validated considering a liquid-rocket benchmark comprised of liquid-oxygen (LOX) and gaseous-hydrogen (GH2) streams. The model accounts for real-fluid thermodynamics and transport properties, making use of the PR-EoS and the Chung transport models. First, the development of a real-fluid model (RFM) with artificial neural network is described in detail. Then, the numerical results of the transcritical mixing layer (LOX/GH2) benchmark are presented and analyzed in terms of accuracy and computational ef-ficiency. Results of the overall implementation indicate that the combined OpenFOAM and ML approach provides a speed-up factor higher than seven, while preserving the original solver accuracy.

Numerical simulations of standard situations in the transition region from gas kinetics to fluid dynamics at small Mach numbers indicate a clear dependence of the simulation results on the underlying kinetic model (here: nonlinear and linearized Boltzmann collision operator vs. BGK relaxation model). We develop an improved mathematical framework (trace theory) to explain these differences. In particular we reveal certain deficiencies for the classical BKG system as well as for the standard Navier Stokes approach.

Magnetorheological (MR) fluids have been known to react to magnetic fields of sufficient magnitudes. While in the presence of the field the material develops a yield stress. The tunable property has made it attractive in e.g. semi-active damper applications in vibration control domain in particular. Within the context of a given application the fluids can be exploited in at least one of the fundamental operating modes of which the so-called gradient pinch mode has been least explored. Contrary to the other operating modes, the MR fluid volume in the flow channel is exposed to a non-uniform magnetic field in such a way that the Venturi-like contraction is developed in a flow channel solely by means of a solidified material in the regions near the walls rather than mechanically driven changes of the channel’s geometry. The pinch mode rheology of the material has made it a potential candidate in developing on a new category of MR valves. By convention, a pinch mode valve features a single flow channel with poles over which non-uniform magnetic field is induced. In this study the authors examine ways of extending the dynamic range of pinch mode valves by employing a number of such arrangements (stages) in series. To accomplish this, the authors developed a prototype of a multi-stage (three-stage) valve, and then compared its performance against that of a single-stage valve across a wide range of hydraulic and magnetic stimuli. To summarize, improvements in the pinch mode valve dynamic range are evident, however, at the same time it is hampered by the presence of serial air gaps in the flow channel.

One of the operational challenges for the use of bentonite pellets as a sealing material in the abandonment of offshore fields consists in their disposition inside the well. This study aims to analyze the interaction of fluid media, consisting of saline solutions (NaCl, CaCl2 and KCl) and organic compounds (diesel, glycerin and olefin), with bentonite pellets, aiming its application as displacement fluid in offshore oil well abandonment operations. The physical integrity of the bentonite pellets in contact with the fluids was verified through visual inspections and dispersibility tests. Linear swelling tests were also performed to evaluate the potential for swelling of pellets in deionized water after contact with the fluid media. The results indicated that NaCl, CaCl2 and KCl solutions completely compromise the physical integrity of the pellets, while diesel and olefin showed the best responses regarding the structural preservation. Futhermore, the linear swelling tests showed that, even after the contact with diesel and olefin for 1 hour, bentonite pellets have reached a total swelling in water of 78%, after 24 hours. In this way, diesel and olefin proved to be highly promising alternatives to be used as displacement fluids for bentonite pellets in wells to be abandoned in a submarine environment.

In recent years, applying deep learning to solve physics problems has attracted much attention. Data-driven deep learning methods produce operators that can learn solutions to the whole system of partial differential equations. However, the existing methods are only evaluated on simple flow equations (e.g., Burger's equation), and only consider the generalization ability on different initial conditions. In this paper, we construct CFDBench, a benchmark with four classic problems in computational fluid dynamics (CFD): lid-driven cavity flow, laminar boundary layer flow in circular tubes, dam flows through the steps, and periodic Karman vortex street. Each flow problem includes data with various boundary conditions, fluid physical properties, and domain geometries. Compared to existing datasets, the advantages of CFDBench are (1) comprehensive. It contains common physical parameters such as velocity, pressure, and cavity fraction. (2) realistic. It is very suitable for deep learning solutions of fluid mechanics equations. (3) challenging. It has a certain learning difficulty, prompting to find models with strong learning ability. (4) standardized. CFDBench facilitates a comprehensive and fair comparison of different deep learning methods for CFD. We make appropriate modifications to popular deep neural networks to apply them to CFDBench and enable the accommodation of more changing inputs. The evaluation on CFDBench reveals some new shortcomings of existing works and we propose possible directions for solving such problems.

This study focuses on the aerodynamic optimization of the re-entry capsule (REC) Orion Crew Exploration Vehicle (CEV) module, evaluating its performance using computational fluid dynamics (CFD). Three different models, namely Baseline, 2-Duct, and 4-Duct, are investigated under a wide range of flow speeds, from supersonic (Ma=1.6) to hypersonic (Ma=6) regimes. Thermofluids aspects, drag coefficient, surface heat flux, and the effectiveness of the modified geometry are assessed using aerodynamic and temperature-based models. The results show that the introduction of ducts in the 2-Duct and 4-Duct models leads to an average decrease in the drag coefficient of approximately 2.1% and 2.9%, respectively, compared to the baseline model, across all Mach numbers. The maximum reduction in drag coefficient is 3.55%, observed at Ma=1.4 using the 4-Duct capsule. However, it is found that the addition of extra ducts to the model increases the maximum heat transfer rate. Specifically, the heat flux is increased by up to 69% for the 4-Duct model at Ma=6, compared to the baseline model. On average, the heat flux is increased by approximately 28.6% for all conditions. The findings indicate that the introduction of ducts in the REC model improves its aerothermodynamic performance by reducing drag but also increases the heat transfer rate on the surface.

Computational Fluid Dynamics (CFD)-based simulation has been the traditional way to model complex industrial systems and processes. One very large and complex industrial system that has benefited from CFD-based simulations is the steel blast furnace. The problem with the CFD-based simulation approach is that it tends to be very slow to generate data. The CFD-only approach may not be fast enough for use in real-time decision-making. To address this issue, in this work, the authors propose the use of machine learning techniques to train and test models based on data generated via CFD simulation. Regression models based on neural networks are compared to tree boosting models. In particular, several areas (tuyere, raceway, and shaft) of the blast furnace are modeled using these approaches. The results of the model training and testing are presented and discussed. The obtained R2 metrics are, in general, very high. The results look promising and may help to improve the efficiency of operator and process engineer decision-making when running a blast furnace.

In this paper, we propose a novel approach to utilize silicon nanowires as high-sensitivity pH sensors. Our approach works based on fixing the current bias of silicon nanowires Ion Sensitive Field Effect Transistors (ISFETs) and monitor the resulting drain voltage as the sensing signal. By fine tuning the injected current levels, we can optimize the sensing conditions according to different sensor requirements. This method proves to be highly suitable for real-time and continuous measurements of biomarkers in human biofluids. To validate our approach, we conducted experiments, with real human sera samples to simulate the composition of human interstitial fluid (ISF), using both the conventional top-gate approach and the optimized constant current method . We successfully demonstrated pH sensing within the physiopathological range of 6.5 to 8, achieving an exceptional level of accuracy in this complex matrix. Specifically, we obtained a maximum error as low as 0.92\% (equivalent to 0.07 pH unit) using the constant-current method at the optimal current levels (1.71\% for top-gate). Moreover, by utilizing different pools of human sera with varying total protein content, we demonstrated that the protein content among patients does not impact the sensors' performance in pH sensing. Furthermore, we tested real-human ISF samples collected from volunteers. The obtained accuracy in this scenario was also outstanding, with an error as low as 0.015 pH unit using the constant-current method and 0.178 pH unit in traditional top-gate configuration.

Backgroumd: The feeling of nasal obstruction is one of the most complaints of the Ear Nose and Throats (ENT) patients. The reason of this complaint is variable, such as Nasal Septal Deviation (NSD). NSD is a significant obstacle to normal respiration and the volume of air entering the lungs. Understanding how the deviation causes the obstruction is so important, because it leads to better management of this disease. Rhinomanometry and acoustic rhinometry are methods that are used for objective evaluation of upper airway, but they are semi invasive and the accuracy are not guaranteed. With development of Computed Tomography (CT scan) and Computational Fluid Dynamics (CFD), numerical studies on airflow in different parts of the nasal cavity have been performed. Objectives: The purpose of this study was to compare nasal airflow patterns between patient with NSD and healthy nasal cavity using a computational fluid dynamics (CFD) Methods: A patient with NSD and a healthy human were selected. Using CFD, the maximal airflow velocity, nasal resistance, maximal Wall Shear Stress (WSS), and pressure drop in bilateral nostrils of both cases were assessed. Results: Pressure and velocity profiles are evaluated at a mass flow rate of 17.4 Liters Per Minute (LPM). The velocity profile shows an abnormal flow profile in the septal deviated nasal cavity and the peak velocity is observed at the middle nasal region, whereas this point is at the nasal valve level in a healthy nasal cavity. Wall shear stress (WSS) caused by NSD is lower than in normal nasal cavities. The pressure drop in a nasal cavity with deviated septum is higher than in a healthy nasal cavity. Based on the results of this investigation nasal resistance in NSD was higher than in normal, healthy nasal cavity. Conclusions: NSD plays an important role in nasal airflow regime and it results in the feeling of obstruction comparing to normal nasal cavity. Also there is a promising future for CFD to become a useful tool in understanding airflow physiology and pathology.

In this paper, a sensitivity sensor of dual-core photonic crystal fiber (DC-PCF) filled with magnetic liquid is introduced and investigated by the finite element method (FEM). To regulate the energy coupling involving the two cores, the magnetic fluid is filled into the pore between the two cores. To adjust the coupling between the supermodes in the DC-PCF, the refractive index of the magnetic fluid-filled air hole may change due to the external magnetic field. This specifically created a magnetic fluid-filled DC-PCF, the magnetic fluid-filled hole is not used as the core for energy transmission, thus avoiding transmission loss. The dip wavelength and the magnetic field displayed an excellent linear connection between 80 and 260 Oe, depending on the numerical data. The detection sensitivity of the magnetic field reached 515.75 pm/Oe at a short fiber length of 482 m. The designed magnetic fluid-filled DC-PCF has high sensitivity and small volume and has great application prospects in medical and industrial field magnetic field detection.

The mechanical effects of membrane compositional inhomogeneities are analyzed in a process analogous of neck formation in cellular membranes. We cast on the Canham-Helfrich model of fluid membranes with both the spontaneous curvature and the surface tension being non-homogeneous functions along the cell membrane. The inhomogeneous distribution is determined by the equilibrium mechanical equations and the boundary conditions as considered in the axisymmetric setting compatible with the necking process. To establish the role played by mechanical inhomogeneity, we focus on the catenoid, a surface of zero mean curvature. Analytic solutions are shown to exist for the spontaneous curvature and the constrictive forces in terms of the border-radii. Our theoretical analysis shows that the inhomogeneous distribution of spontaneous curvature in a mosaic-like neck constrictional forces potentially contributing to the membrane scission under minimized work in living cells.

Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates are one of the most difficult pathogens to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 indicated for the treatment of infections due to CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported higher than all-cause mortality rate in patients treated with cefiderocol. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Recent results have shown that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here we describe molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Methods: Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were subjected to whole genome sequencing and transcriptional analysis to identify mutations and expression changes associated with cefiderocol heteroresistance. The impact of these mutations on the pharmacodynamic activity of cefiderocol was assessed via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses showed significant modifications in levels of expression of genes associated with these functions. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes’ expression was reduced. One of the mutations common to both heteroresistant strains mapped within pipA, a gene associated with iron homeostasis in other species. Static time-kill assays showed that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin, the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. Conclusions: We conclude that exposing CRAB to fluids containing high HSA facilitates the rise of heteroresistance associated with point mutations and upregulation of genes coding for β-lactamases and biofilm formation.