DETERMINING THE OPTIMAL SITE LOCATION OF GNSS BASE STATIONS

The relative positioning technique plays an essential role in Global Navigation Satellite System (GNSS) surveys. Simultaneous observation at base and rover stations eliminates the majority of error sources thus the quality of a positioning solution can be substantially improved. However, topographic obstruction is still a key issue affecting positioning quality. In this study, an integrated approach for analyzing the impact of topographic obstruction on GNSS relative positioning has been developed. By considering varied satellite geometry according to actual terrain variation, this approach can be used to realistically determine satellite visibility condition for a specific base station with respect to any rover station. Furthermore, a base station quality index (BSQI) is proposed as an explicit indication of the sufficiency in a relative positioning. By incorporating the proposed approach, one can immediately identify an optimal site location for a GNSS base station with subsequent GNSS field survey thus achieved in a more reliable and cost-efficient manner

Inlet and Outlet Boundary Conditions and Uncertainty Quantification in Volumetric Lattice Boltzmann Method for Image-Based Computational Hemodynamics

Inlet and outlet boundary conditions (BCs) play an important role in newly emerged image-based computational hemodynamics for blood flows in human arteries anatomically extracted from medical images. We developed physiological inlet and outlet BCs based on patients’ medical data and integrated them into the volumetric lattice Boltzmann method. The inlet BC is a pulsatile paraboloidal velocity profile, which fits the real arterial shape, constructed from the Doppler velocity waveform. The BC of each outlet is a pulsatile pressure calculated from the three-element Windkessel model, in which three physiological parameters are tuned by the corresponding Doppler velocity waveform. Both velocity and pressure BCs are introduced into the lattice Boltzmann equations through Guo’s non-equilibrium extrapolation scheme. Meanwhile, we performed uncertainty quantification for the impact of uncertainties on the computation results. An application study was conducted for six human aortorenal arterial systems. The computed pressure waveforms have good agreement with the medical measurement data. A systematic uncertainty quantification analysis demonstrates the reliability of the computed pressure with associated uncertainties in the Windkessel model. With the developed physiological BCs, the image-based computation hemodynamics is expected to provide a computation potential for the noninvasive evaluation of hemodynamic abnormalities in diseased human vessels

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations

Identification of Glycine Receptor α3 as a Colchicine-Binding Protein

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations

Aberrant Sensory Gating of the Primary Somatosensory Cortex Contributes to the Motor Circuit Dysfunction in Paroxysmal Kinesigenic Dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits. The role of synchronized gamma oscillations in sensory gating is an important mechanism of automatic cortical inhibition. The patterns of gamma oscillations have been used to characterize neurophysiological features of many neurological diseases, including epilepsy and MDs. This study was aimed to investigate the features of gamma synchronizations in PKD. In the paired-pulse electrical-stimulation task, we recorded the magnetoencephalographic data with distributed source modeling and time-frequency analysis in 19 patients of newly-diagnosed PKD without receiving pharmacotherapy and 18 healthy controls. In combination with the magnetic resonance imaging, the source of gamma oscillations was localized in the primary somatosensory cortex. Somatosensory evoked fields of PKD patients had a reduced peak frequency (p < 0.001 for the first and the second response) and a prolonged peak latency (the first response p = 0.02, the second response p = 0.002), indicating the synchronization of gamma oscillation is significantly attenuated. The power ratio between two responses was much higher in the PKD group (p = 0.013), indicating the incompetence of activity suppression. Aberrant gamma synchronizations revealed the defective sensory gating of the somatosensory area contributes the pathogenesis of PKD. Our findings documented disinhibited cortical function is a pathomechanism common to PKD and epilepsy, thus rationalized the clinical overlaps of these two diseases and the therapeutic effect of antiepileptic agents for PKD. There is a greater reduction of the peak gamma frequency in PRRT2-related PKD than the non-PRRT PKD group (p = 0.028 for the first response, p = 0.004 for the second response). Loss-of-function PRRT2 mutations could lead to synaptic dysfunction. The disinhibiton change on neurophysiology reflected the impacts of PRRT2 mutations on human neurophysiology

Determining the optimal site location of GNSS base stations

The relative positioning technique plays an essential role in Global Navigation Satellite System (GNSS) surveys. Simultaneous observation at base and rover stations eliminates the majority of error sources thus the quality of a positioning solution can be substantially improved. However, topographic obstruction is still a key issue affecting positioning quality. In this study, an integrated approach for analyzing the impact of topographic obstruction on GNSS relative positioning has been developed. By considering varied satellite geometry according to actual terrain variation, this approach can be used to realistically determine satellite visibility condition for a specific base station with respect to any rover station. Furthermore, a base station quality index (BSQI) is proposed as an explicit indication of the sufficiency in a relative positioning. By incorporating the proposed approach, one can immediately identify an optimal site location for a GNSS base station with subsequent GNSS field survey thus achieved in a more reliable and cost-efficient manner

The Effects of the Hepatitis C Virus NS3 Protein on Cell Adhesion and Migration Ability

C型肝炎病毒的NS3為一多功能性之非結構性蛋白質，具有絲胺酸蛋白酶、核醣核酸水解酶和核醣核酸解旋酶的酵素活性。Integrin是一種位於細胞表面負責與細胞外基質交互作用的穿膜受器。目前研究顯示，integrin可以調控細胞生長、存活、分化和型態的改變等訊號。研究指出表現NS3可造成纖維母細胞在養分缺乏的環境下增生，NS3也被證明具有誘導細胞轉型的能力。本實驗室發現NS3在NS4A的輔助下會發生內部截切，且NS3蛋白酶活性對於細胞轉型扮演重要的角色；因此我們認為NS3蛋白質為肝癌形成的重要因子。實驗室結果指出NS3蛋白質和細胞內生性integrin β1有相互作用，本研究更進一步探討NS3是否影響細胞的貼附、移動能力和integrin下游訊號傳遞。利用不同的細胞外基質，進行細胞貼附實驗，結果發現細胞貼附能力隨著NS3蛋白質表現量而明顯下降；而在傷口癒合分析實驗中，表現NS3蛋白質的細胞移動能力有提升的趨勢。利用西方墨點法分析表現NS3蛋白質的細胞integrin及下游訊號paxillin活化的變化，結果顯示細胞不論貼附在poly-L-lysine、fibronectin和collagen的細胞外基質上時，NS3蛋白質的表現都會造成integrin β1總表現量下降；但貼附在fibronectin時，integrin β1活化程度的下降比較明顯。當表現NS3蛋白質的細胞貼附在collagen上時，其integrin β1下游訊號傳遞paxillin磷酸化比例有下降的趨勢。NS3是否藉由影響細胞integrin β1的表現量，並對於integrin辦認不同細胞外基質的形態(α2β1和α5β1)造成差異性影響，導致下游訊號有所改變，進而調控細胞貼附和移動有待進一步確認。本研究對NS3影響細胞貼附和移動之瞭解，提供了進一步探討NS3促使細胞癌化可能作用機制的一個方向。Hepatitis C virus (HCV) non-structural protein 3 (NS3) is a multiple functional protein that possesses serine protease, NTPase and RNA helicase activities. Integrins, which are heterodimeric membrane glycoproteins, are cell-surface receptors mediating cell-matrix adhesion and initiate multiple intracellular signal transductions in response to ligand occupancy. Through these signaling pathways, integrins play important roles in regulating cell proliferation, cell survival, cell morphological changes and cell differentiation. Previous studies have demonstrated the abilities of the HCV NS3 to enhance cell growth rate, to allow culture cells to grow in low serum condition, and to induce cell transformation. Therefore, NS3 was proposed to be an important factor in tumorigenesis. Studies in our laboratory have demonstrated that the NS3 has an NS4A-dependent internal NS3 cleavage activity, and the protease activity of the NS3 plays an important role in cell transforming activity. In addition, an interaction between the NS3 protein and endogenous integrin β1 was demonstrated. In this study, whether NS3 affects cell adhesion and migration was examined. A possible association of the effects with integrin signaling was further analyzed. Adhesion assay and wound healing assay were performed. The results showed that NS3 reduced cell adhesion and promoted cell migration. In addition, NS3 reduced the expression levels of total integrin β1 no matter poly-L-lysine, fibronectin, or collagen was used as the extracellular matrix, but showed a reduction in the active form integrin β1 only when fibronectin was used. In addition, the ratio of phosphorylated paxillin to total was reduced in NS3 expressing cells that were attached on collagen. Whether NS3 down-regulates integrin expression causing an inhibitory effect on cell adhesion needs to be further confirmed. In addition, the regulation can be complicated and depends on various integrin heterodimers. These results provide a possible direction in further studying the mechanisms of NS3 involved in HCV turmorigenesis

The Effects of the Hepatitis C Virus NS3 Protein on Cell Adhesion and Migration Ability

C型肝炎病毒的NS3為一多功能性之非結構性蛋白質，具有絲胺酸蛋白酶、核醣核酸水解酶和核醣核酸解旋酶的酵素活性。Integrin是一種位於細胞表面負責與細胞外基質交互作用的穿膜受器。目前研究顯示，integrin可以調控細胞生長、存活、分化和型態的改變等訊號。研究指出表現NS3可造成纖維母細胞在養分缺乏的環境下增生，NS3也被證明具有誘導細胞轉型的能力。本實驗室發現NS3在NS4A的輔助下會發生內部截切，且NS3蛋白酶活性對於細胞轉型扮演重要的角色；因此我們認為NS3蛋白質為肝癌形成的重要因子。實驗室結果指出NS3蛋白質和細胞內生性integrin β1有相互作用，本研究更進一步探討NS3是否影響細胞的貼附、移動能力和integrin下游訊號傳遞。利用不同的細胞外基質，進行細胞貼附實驗，結果發現細胞貼附能力隨著NS3蛋白質表現量而明顯下降；而在傷口癒合分析實驗中，表現NS3蛋白質的細胞移動能力有提升的趨勢。利用西方墨點法分析表現NS3蛋白質的細胞integrin及下游訊號paxillin活化的變化，結果顯示細胞不論貼附在poly-L-lysine、fibronectin和collagen的細胞外基質上時，NS3蛋白質的表現都會造成integrin β1總表現量下降；但貼附在fibronectin時，integrin β1活化程度的下降比較明顯。當表現NS3蛋白質的細胞貼附在collagen上時，其integrin β1下游訊號傳遞paxillin磷酸化比例有下降的趨勢。NS3是否藉由影響細胞integrin β1的表現量，並對於integrin辦認不同細胞外基質的形態(α2β1和α5β1)造成差異性影響，導致下游訊號有所改變，進而調控細胞貼附和移動有待進一步確認。本研究對NS3影響細胞貼附和移動之瞭解，提供了進一步探討NS3促使細胞癌化可能作用機制的一個方向。Hepatitis C virus (HCV) non-structural protein 3 (NS3) is a multiple functional protein that possesses serine protease, NTPase and RNA helicase activities. Integrins, which are heterodimeric membrane glycoproteins, are cell-surface receptors mediating cell-matrix adhesion and initiate multiple intracellular signal transductions in response to ligand occupancy. Through these signaling pathways, integrins play important roles in regulating cell proliferation, cell survival, cell morphological changes and cell differentiation. Previous studies have demonstrated the abilities of the HCV NS3 to enhance cell growth rate, to allow culture cells to grow in low serum condition, and to induce cell transformation. Therefore, NS3 was proposed to be an important factor in tumorigenesis. Studies in our laboratory have demonstrated that the NS3 has an NS4A-dependent internal NS3 cleavage activity, and the protease activity of the NS3 plays an important role in cell transforming activity. In addition, an interaction between the NS3 protein and endogenous integrin β1 was demonstrated. In this study, whether NS3 affects cell adhesion and migration was examined. A possible association of the effects with integrin signaling was further analyzed. Adhesion assay and wound healing assay were performed. The results showed that NS3 reduced cell adhesion and promoted cell migration. In addition, NS3 reduced the expression levels of total integrin β1 no matter poly-L-lysine, fibronectin, or collagen was used as the extracellular matrix, but showed a reduction in the active form integrin β1 only when fibronectin was used. In addition, the ratio of phosphorylated paxillin to total was reduced in NS3 expressing cells that were attached on collagen. Whether NS3 down-regulates integrin expression causing an inhibitory effect on cell adhesion needs to be further confirmed. In addition, the regulation can be complicated and depends on various integrin heterodimers. These results provide a possible direction in further studying the mechanisms of NS3 involved in HCV turmorigenesis