A neural network-based PDE solving algorithm with high precision.

The consumption of solving large-scale linear equations is one of the most critical issues in numerical computation. An innovative method is introduced in this study to solve linear equations based on deep neural networks. To achieve a high accuracy, we employ the residual network architecture and the correction iteration inspired by the classic iteration methods. By solving the one-dimensional Burgers equation and the two-dimensional heat-conduction equation, the precision and effectiveness of the proposed method have been proven. Numerical results indicate that this DNN-based technique is capable of obtaining an error of less than 10-7. Moreover, its computation time is less sensitive to the problem size than that of classic iterative methods. Consequently, the proposed method possesses a significant efficiency advantage for large-scale problems.

Effect of thread depth and thread pitch on the primary stability of miniscrews receiving a torque load : A finite element analysis.

PURPOSE: We have been developing a new type of miniscrew to specifically withstand orthodontic torque load. This study aimed to investigate the effect of thread depth and thread pitch on the primary stability of these miniscrews if stressed with torque load. METHODS: Finite element analysis (FEA) was used to evaluate the primary stability of the miniscrews. For thread depth analysis, the thread depth was set to 0.1-0.4 mm to construct 7 models. For thread pitch analysis, the thread pitch was set to 0.4-1.0 mm to construct another 7 models. A torque load of 6 Nmm was applied to the miniscrew, and the other parameters were kept constant for the analyses. Maximum equivalent stress (Max EQV) of cortical bone and maximum displacement of the miniscrews (Max DM) were the indicators for primary stability of the miniscrew in the 14 models. RESULTS: In the thread depth analysis, Max DM increased as the miniscrew thread depth increased, while Max EQV was smallest in model 3 (thread depth = 0.2, Max EQV = 8.91 MPa). In the pitch analysis, with an increase of the thread pitch, Max DM generally exhibited a trend to increase, while Max EQV of cortical bone showed a general trend to decrease. CONCLUSION: Considering the data of Max DM and Max EQV, the most appropriate thread depth and thread pitch of the miniscrews in our model was 0.2 and 0.7 mm, respectively. This knowledge may effectively improve the primary stability of newly developed miniscrews.

Optimization Analysis of Two-Factor Continuous Variable between Thread Depth and Pitch of Microimplant under Toque Force.

Microimplant, an anchorage device, is widely applied in clinical orthodontic treatment. Since tooth torque is required to be controlled during orthodontic tooth movement, a novel microimplant needs to be developed to apply better torque force during orthodontic. In this study, the optimal value ranges of thread depth and pitch under toque force were studied for choosing microimplant with relevant value ranges in clinical design from biomechanical perspective. Finite element analysis (FEA) and optimization design technology were used for accessing the optimal value ranges of thread depth and pitch under toque force. Thread depth (D) (0.1 mm to 0.4 mm) and pitch (P) (0.4 mm to 1 mm) were used as continuous variables, with the other parameters as constant, and the optimal value ranges were obtained by analyzing the tangent slope and sensitivity of the response curve. When a torque force of 6 Nmm was applied on the microimplant, the maximum equivalent stress (Max EQV) of cortical bone and maximum displacements (Max DM) of microimplant were analysis indexes. When 0.55 mm ≤ P ≤ 1 mm, the Max EQV of cortical bone was relatively smaller with less variation range. When 0.1 mm ≤ D ≤ 0.35 mm, the Max DM of microimplant was relatively smaller with less variation range. So in conclusion, the initial stability of microimplants with pitch 0.55 mm ≤ P ≤ 1 mm and thread depth 0.1 mm ≤ D ≤ 0.35 mm was better with the torque force applied.

Numerical Investigation of T-Shaped Microfluidic Oscillator with Viscoelastic Fluid.

Oscillatory flow has many applications in micro-scaled devices. The methods of realizing microfluidic oscillators reported so far are typically based on the impinging-jet and Coanda effect, which usually require the flow Reynolds number to be at least at the order of unity. Another approach is to introduce elastomeric membrane into the microfluidic units; however, the manufacturing process is relatively complex, and the membrane will become soft after long-time operation, which leads to deviation from the design condition. From the perspective of the core requirement of a microfluidic circuit, i.e., nonlinearity, the oscillatory microfluidic flow can be realized via the nonlinear characteristics of viscoelastic fluid flow. In this paper, the flow characteristics of viscoelastic fluid (Boger-type) in a T-shaped channel and its modified structures are studied by two-dimensional direct numerical simulation (DNS). The main results obtained from the DNS study are as follows: (1) Both Weissenberg (Wi) number and viscosity ratio need to be within a certain range to achieve a periodic oscillating performance; (2) With the presence of the dynamic evolution of the pair of vortices in the upstream near the intersection, the oscillation intensity increases as the elasticity-dominated area in the junction enlarges; (3) Considering the simplicity of the T-type channel as a potential oscillator, the improved structure should have a groove carved toward the entrance near the upper wall. The maximum oscillation intensity measured by the standard deviation of flow rate at outlet is increased by 129% compared with that of the original standard T-shaped channel under the same condition. To sum up, with Wi number and viscosity ratio within a certain range, the regular periodic oscillation characteristics of Oldroyd-B type viscoelastic fluid flow in standard T-shaped and its modified channels can be obtained. This structure can serve as a passive microfluidic oscillator with great potential value at an extremely low Reynolds number, which has the advantages of simplicity, no moving parts and fan-out of two.

Thread shape affects the stress distribution of torque force on miniscrews: a finite element analysis.

This study aimed to investigate the effect of miniscrews thread shape on the stress distribution receiving a torque load. Seven thread shapes (S,V1,V2,B1,B2,R1,R2) models were constructed and a 6 Nmm-torque load was applied. The order of maximum equivalent stress (EQV) value was V1 > V2 > B1 > R1 > R2 > B2 > S. The order of maximum displacement of miniscrew (Max DM) value was S > B2 > R1 = V1 > B1 > V2 > R2. Model R2 may be the most appropriate thread shape affording a torque force.

DPP-4 inhibitor saxagliptin ameliorates oxygen deprivation/reoxygenation-induced brain endothelial injury.

Cardiovascular diseases are the main cause of death and disability among diabetes patients. Atherosclerosis-associated stroke is one of the most severe complications in diabetes patients. DPP-4 inhibitors are a class of potent anti-glycemic agents used to treat diabetes. Recently, some DPP-4 inhibitors have been shown to have cardiovascular benefits. In this study, we reveal that saxagliptin, one of the most widely used DPP-4 inhibitors, exhibits vascular protective effects against oxygen and glucose depletion/reoxygenation (OGD/R) in human brain vascular endothelial cells. Our data show that DPP-4 is fairly expressed in brain endothelial cells and its expression is induced by OGD/R. The results of MTT assay show that inhibition of DPP-4 by saxagliptin ameliorates OGD/R-induced reduced cell viability, and LDH assay demonstrated that saxagliptin reduces cellular toxicity. Furthermore, we show that saxagliptin mitigates OGD/R-induced collapse of mitochondrial membrane potential (MMP). Saxagliptin also reduces oxidative stress-induced release of 4-HNE and the NAPDH oxidase catalytic subunit NOX-4. At the molecular level, saxagliptin suppresses OGD/R-induced expression of pro-inflammatory cytokines and production of vascular adhesion molecules including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1), vascular cellular adhesion molecule 1 (VCAM-1), and E-selectin. Mechanistically, saxagliptin inhibits activation of the NF-κB pathway by OGD/R via its inhibitory effect on nuclear p65 and NF-κB promoter activity. Collectively, our study explicitly demonstrates the cellular protective effect of saxagliptin against OGD/R-induced brain endothelial injury. Our findings extend our recognition of the protective roles of DPP-4 inhibitors in brain vascular cells.

Anagliptin protects neuronal cells against endogenous amyloid ß (Aß)-induced cytotoxicity and apoptosis.

Excessive generation and accumulation of amyloid-ß (Aß) fragments by familial mutations of amyloid precursor protein (APP) and presenilin 1 (PS1) play a key role in causing oxidative stress, mitochondrial abnormalities and neuronal apoptosis in Alzheimer's disease (AD). Anagliptin, a novel DPP-4 inhibitor, is a clinical drug for the management of type II diabetes approved for use in 2012. Little on the pharmacological function of anagliptin against Aß-induced cytotoxicity in neuronal cells is known. Here, we examined the protective capacities of anagliptin against cytotoxicity in N2a neuronal cells overexpressing APP Swedish mutant and PS1 exon 9 deletion mutant (N2a/Swe.D9). Our results demonstrate that anagliptin reduced the production of ROS and the expression of NADPH oxidase 4 (NOX-4) in N2a/Swe.D9 cells. We also reported that anagliptin activates the antioxidant system by increasing the level of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity. Notably, anagliptin is able to improve mitochondrial function by elevating mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production. Additionally, our results demonstrate that anagliptin decreased the vulnerability of cells to hydrogen peroxide (H2O2)-induced secondary insult by increasing cell viability and reducing the secretion of lactate dehydrogenase (LDH) and high mobility group box 1 protein (HMGB-1). Importantly, we found that treatment with anagliptin suppressed the mitochondrial-dependent apoptosis pathway by preventing the translocation of cytochrome C, reducing cleavage of caspase-3, and the inhibiting expression of Bax. These results implicate that anagliptin may have potential as a therapeutic agent for AD treatment.

Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway.

Mitochondrial biogenesis deficits in neuronal cells are associated with the pathological progression of neurodegenerative diseases. Resistin, a secretory adipocytokine, possesses multiple physiological functions in diverse cells and tissues. However, the effects of resistin on mitochondrial biogenesis in neuronal cells are still elusive. In the current study, we found that resistin caused a sustainable decrease in mitochondrial contents, including mitochondrial DNA/nuclear DNA ratio (mtDNA/nDNA), mitochondrial mass, cytochrome b protein expression, and cytochrome c oxidase activity, which were correlated with "loss of mitochondrial function" including reduced mitochondrial respiration rate and ATP production in human SH-SY5Y neuronal cells. Indeed, resistin treatment destroyed the expression of peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, as well as its downstream target genes including nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Notably, overexpression of PGC-1α could completely rescue mitochondrial biogenesis and mitochondrial deficits induced by resistin. Mechanistically, inhibition of 5'-adenosine monophosphate-activated protein kinase (AMPK) was shown to mediate the inhibitory effects of resistin on mitochondrial biogenesis.

Comparison of novel granulated pellet-containing tablets and traditional pellet-containing tablets by artificial neural networks.

Novel granulated pellets technique was adopted to prepare granulated pellet-containing tablets (GPCT). GPCT and traditional pellet-containing tablets (PCT) were prepared according to 29 formulations devised by the Design Expert 7.0, with doxycycline hydrochloride as model drug, blends of Eudragit FS 30D and Eudragit L 30D-55 as coating materials, for the comparison study to confirm the superiority of GPCT during compaction. Eudragit FS 30D content, coating weight gain, tablet hardness and pellet size were chosen as influential factors to investigate the properties and drug release behavior of tablets. The correlation coefficients between the experimental values and the predicted values by artificial neural networks (ANNs) for PCT and GPCT were 0.9474 and 0.9843, respectively, indicating the excellent prediction of ANNs. The similarity factors (f2) for release profiles of GPCT and the corresponding original pellets were higher than those of PCT, suggesting that the excipient layer of granulated pellets absorbed the compressing force and protected the integrity of coating films during compaction.

Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma.

Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain (P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors (P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade (P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score (P = .03), and high CREB-1 expression correlated positively with mean tumor diameter (P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.

A hypermotor seizure with a focal orbital frontal lesion originating in the insula: a case report.

We present herein the case of a patient with a focal orbital frontal lesion on magnetic resonance imaging (MRI), but an insular onset of seizures. A 15-year-old boy suffered from hypermotor seizures for 9 years. In his seizures, he initially had a sensation that sounds were distant, and then his consciousness became impaired. After a short period of tonic activity, violent activities occurred, such as kicking or gripping some objects and shaking. MRI showed a focal cortical abnormality in the right orbital frontal lobe. [(18)F]FDG-PET revealed diffuse hypometabolism in the right frontal lobe, especially in the same site as the cortical lesion on MRI. The seizure onset zone was localized in the right anterior insula by intracranial recording. A resection of the right anterior insula and a partial disconnection of the frontal lobe were performed, rendering the patient seizure-free.

Low- and high-frequency electric cortical stimulation suppress the ferric chloride-induced seizures in rats.

The clinic treatment of epilepsy with epileptic foci overlapped with eloquent cortex is not satisfactory. In this study we investigated the direct effects of low- and high-frequency electric cortical stimulation (ECS) on ferric chloride-induced seizures in the experimental rats. Results showed that spontaneous seizures were observed in all rats during the EEG recording after the intracortical injection of ferric chloride solution into left sensorimotor cortex. One-hertz or 100-Hz ECS with 0.3 ms duration and 0.1 mA amplitude square pulses in 1h on the cortical lesioned area significantly decreased the number of seizures compared with that of the non-stimulation control group. The mean duration time of seizures in 1-Hz or 100-Hz groups was apparently shorter than that in the control group. In brief, this study showed that both low- and high-frequency ECS suppressed the seizures induced by ferric chloride in rats, indicating their potential treatment effects on epilepsy in clinic.