There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension ...introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.
Summary
Background
The pathogenesis of gastro‐oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive‐affective ...evaluation of visceral sensitivity.
Aims
To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD.
Methods
Patients with chronic reflux symptoms and negative endoscopy underwent 24‐hour impedance‐pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient‐reported outcomes, including EHAS, GERD questionnaire (GERDQ), State‐Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded.
Results
We enrolled 105 patients, aged 21‐64 years (mean, 48.8), of whom 58.1% were female; 27 had non‐erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient‐reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05).
Conclusions
EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
The putative modulators for reflux symptom severity.
As fossil fuels and people’s environmental awareness increases, renewable energy is becoming one of the world’s most anticipated areas of development. Taiwan has an outstandingly favorable ...environment for wind farms, and the Taiwanese government actively promotes wind-power generation (such as its “Thousand Wind Turbines Project”). Many wind turbines are expected to be built, driving the development of land-based and offshore wind turbines. Owing to its geographical location, Taiwan is prone to typhoons that bring constant strong winds and torrential rain in the summer. These natural phenomena have caused the collapse of several wind turbine towers in Taiwan in recent years, causing serious economic losses. Typhoon intensity and frequency have been increasing, so identifying the causes of wind turbine collapses and developing corresponding risk reduction measures have become crucial. This study investigates domestic and international wind turbine tower collapses to identify the mechanisms that trigger strong wind-induced wind turbine collapses; to analyze the activation mechanisms of tower collapse and the forces that are exerted on the wind turbines at these times, and to generalize the factors that govern wind turbine collapse. The root cause analysis of strong wind induced damage of wind turbines is applied. Based on the results, remarks concerning risk reduction of accidents involving wind turbines are provided.
•Natural phenomena have collapsed wind turbine towers, causing economic losses.•This study investigates mechanisms that trigger strong wind-induced wind turbine collapses.•Root causes of strong wind-induced damage to, and collapses of, wind turbines are identified.•Methods of reducing the risk of these incidences are developed.
Stroke is a common cause of death worldwide and leads to disability and cognitive dysfunction. Ischemic stroke and hemorrhagic stroke are major categories of stroke, accounting for 68% and 32% of ...strokes, respectively. Each year, 15 million people experience stroke worldwide, and the stroke incidence is rising. Epigenetic modifications regulate gene transcription and play a major role in stroke. Accordingly, histone deacetylase 1 (HDAC1) participates in DNA damage repair and cell survival. However, the mechanisms underlying the role of HDAC1 in stroke pathogenesis are still controversial. Therefore, we investigated the role of HDAC1 in stroke by using a rat model of endothelin-1-induced brain ischemia. Our results revealed that HDAC1 was deregulated following stroke, and its expressional level and enzymatic activity were decreased. We also used MS-275 to inhibit HDAC1 function in rats exposed to ischemic insult. We found that HDAC1 inhibition promoted the infarct volume, neuronal loss, DNA damage, neuronal apoptosis after stroke, and levels of reactive oxygen species and inflammation cytokines. Additionally, HDAC1 inhibition deteriorated the behavioral outcomes of rats with ischemic insult. Overall, our findings demonstrate that HDAC1 participates in ischemic pathogenesis in the brain and possesses potential for use as a therapeutic target.
•A semi-analytical solution for solute transport in the SWPP test was developed.•The proposed solution was developed under fully transient flow.•The long tail of BTC is characteristic of type curves ...for the transient flow model.•The steady-state flow model could result in the overestimation of dispersivity.
The single-well push–pull (SWPP) test has been extensively used in parameter estimation models. Numerous analytical solutions to the problem are available, all of which consider solute transport in a non-uniform flow field from steady radial flow created by the SWPP test. However, the non-uniform flow velocity is based on the Thiem equation and varies in a spatial manner, rather than a temporal manner. No analytical solution has been previously described for the solute transport equation of SWPP under fully transient flow. In this study, the generalized integral transform technique (GITT) was used to develop a new semi-analytical solution for solute transport in the SWPP test under fully transient flow. Four phases of the SWPP test were included: injection, chaser, rest, and extraction. With the proposed solution, the differences between a transient flow SWPP model solution and a piecewise steady-state flow SWPP model solution were non-negligible; such differences increased with decreases in the dimensionless parameter related to aquifer flow properties, which is proportional to transmissivity, aquifer thickness, and porosity, but inversely proportional to the storage coefficient and pumping rate. Additionally, long tails of BTCs are characteristic of type curves under the transient flow model. The long tails of BTCs under transient flow could result in overestimation of dispersivity if the SWPP model uses piecewise steady-state flow, rather than transient flow, for parameter estimation. The proposed semi-analytical solution provides a useful tool for curve-fitting during parameter estimation when the effects of transient flow are significant. The proposed solution can also serve as a performance comparison for testing numerical solutions to the SWPP test.
Background and Aim
Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary ...peristalsis by stimulating 5‐hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM.
Methods
After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid‐esophageal injections of air in 15 patients with IEM. Two separate sessions with 4‐mg oral prucalopride or placebo were randomly performed.
Results
Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% 43–70%) than placebo (45% 33–50%) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09).
Conclusions
Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.
This research presents a comprehensive, sequential ensemble framework meticulously crafted for optimizing investment portfolios, focusing on the construction industry. It employs decision tree-based ...and metaheuristic optimization algorithms to create an efficient stock-selection framework grounded in financial analysis. This approach offers a profitable investment strategy integrated with portfolio optimization while systematically lowering the portfolio investment threshold. In this framework, a web crawler was deployed to gather daily closing prices of stocks from the Taiwan Stock Exchange, along with monthly revenue data and financial statements. Subsequently, decision tree-based models were utilized to pinpoint the fundamental financial indicators with significant explanatory power over revenues. The stock selection conditions aligned with these indicators were optimized through a newly developed metaheuristic algorithm named the forensic-based investigation (FBI) optimizer. The optimal conditions were subsequently integrated with the equal-weighting scheme, mean-variance method, and hierarchical risk parity to identify the most effective investment portfolio strategies. Backtesting results showed that the proposed stock-portfolio investment strategy, optimized through machine learning and a metaheuristic algorithm, is well-suited for construction and all-stock categories. This study equips professional investment advisors or securities investment institutions with a decision-aid expert system for initial stock selection.
•Developing an innovative stock selection strategy based on specific criteria thresholds.•Utilizing machine learning models (RF, XGBoost, and LightGBM) to analyze key financial indicators.•Merging financial analysis with a Forensic-Based Investigation (FBI) algorithm for portfolio construction.•Examining portfolio allocation strategies (EW, MV, and HRP) to maximize investment returns.•Showcasing excess returns through strategic portfolio management in backtesting investments.
Demand has increased for analytical solutions to determine the velocities and dispersion coefficients that describe solute transport with spatial, temporal, or spatiotemporal variations encountered ...in the field. However, few analytical solutions have considered spatially, temporally, or spatiotemporally dependent dispersion coefficients and velocities. The proposed solutions consider eight cases of dispersion coefficients and velocities: both spatially dependent, both spatiotemporally dependent, both temporally dependent, spatiotemporally dependent dispersion coefficient with spatially dependent velocity, temporally dependent dispersion coefficient with constant velocity, both constant, spatially dependent dispersion coefficient with spatiotemporally dependent velocity, and constant dispersion coefficient with temporally dependent velocity. The spatial dependence is linear, while the temporal dependence may be exponential, asymptotical, or sinusoidal. An advection–dispersion equation with these variable coefficients was reduced to a non-homogeneous diffusion equation using the pertinent coordinate transform method. Then, solutions were obtained in an infinite medium using Green’s function. The proposed analytical solutions were validated against existing analytical solutions or against numerical solutions when analytical solutions were unavailable. In this study, we showed that the proposed analytical solutions could be applied for various spatiotemporal patterns of both velocity and the dispersion coefficient, shedding light on feasibility of the proposed solution under highly transient flow in heterogeneous porous medium.
•Solute transport in coastal aquifers subject to tidal fluctuations is calculated.•Variable boundary conditions at the seawater-groundwater interface is used.•Cauchy-Neumann variable boundary ...reflects reality better than Dirichlet-Neumann.
Transport of contaminants in coastal aquifers subject to tidal fluctuations is an important topic and a growing problem due to increasing populations and development in coastal areas. Many studies have used variable boundary conditions to simulate transport behavior at the interface between seawater and groundwater. However, to the best of our knowledge, no analytical solution accounting for variable-concentration boundary conditions exists for plume migration of land-derived contaminants passing through the inland zone of aquifers under tidally induced periodic flow. Here, a two-dimensional (2D) semi-analytical solution for land-derived solute transport was developed with variable boundary conditions at the seaward boundary under tidal fluctuations. The proposed 2D semi-analytical solution was verified through comparison with an existing one-dimensional semi-analytical solution and a 2D numerical solution developed using the finite-element method. Sensitivity analysis was performed to explore factors including hydraulic properties, tidal amplitude, and the location and distribution of initial contaminants, which affect the characteristics of land-derived pollutant transport in coastal aquifers. Through comparison of the calculated masses remaining over time in the aquifer using the proposed semi-analytical solution under two types of variable boundary conditions (Dirichlet-Neumann and Cauchy-Neumann variable boundary conditions), we found that the Cauchy-Neumann variable boundary conditions reflected reality better than did the Dirichlet-Neumann variable boundary conditions. The proposed analytical solution will be useful for obtaining insights into the mechanisms that drive the plume behavior of contaminants such as radionuclides or toxic chemicals released into coastal aquifers of tidally affected systems.
In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen
groups in a ...critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen
. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen
groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.
PDF
