Search

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

Gravity Recovery and Climate Experiment (GRACE) and satellite altimetry are suitable for the precise measurement of terrestrial water storage (TWS) and lake water level variations from space. In this study, two GRACE solutions, namely, spherical harmonics (SH) and mascon (MSC), are utilized with the Global Land Data Assimilation System (GLDAS) model to estimate the spatial and temporal variations of TWS in the Upper Indus Basin (UIB) for the study period of January 2003 to December 2016. The TWS estimated by SH, MSC, and the GLDAS model are consistent and generally show negative trends of -4.47 ± 0.38 mm/year, -4.81 ± 0.49 mm/year, and -3.77 ± 0.46 mm/year, respectively. Moreover, we use the GLDAS model data to understand the roles of variations in land surface state variables (snow water equivalent (SWE), soil moisture, and canopy water storage) in enhancing or dissipating the TWS in the region. Results indicate that SWE, which has a significant contribution to GRACE TWS variability, is an important parameter. Spearman's rank correlations are calculated to demonstrate the relationship of the GLDAS land surface state variables and the GRACE signals. A highly positive correlation between SWE with TWS is estimated by SH and MSC as 0.691 and 0.649, respectively, indicating that the TWS signal is mainly reliant on snow water in the study region. The ground water storages estimated by SH and MSC solutions are nearly stable with slight increasing trends of 0.63 ± 0.48 mm/year and 0.29 ± 0.51 mm/year, respectively. We also take advantage of the potential of satellite altimetry in measuring lake water level variations, and our result indicates that Cryosat-2 SARin mode altimetry data can be used in estimating small water bodies accurately in the high mountainous region of the UIB. Moreover, the climate indices data of El-Niño Southern Oscillation and Pacific Decadal Oscillation are analyzed to determine the influence of pacific climatic variability on TWS.

Those who are challenged by dependency on prescription drugs or suffer drug addictions have few options available to them for recovery, such as psychotherapy and physiotherapy. Here we present a new approach with clinical examples involving stimulant addiction or overdose of hypnotic drugs that were received BIOCERAMIC Resonance, which was developed based on concept of 12 meridian channels of traditional Chinese medicine, and has successful withdrawal or dose reduction benefits. We describe the whole process and the clinical outcome. And by help of our previous publication on functional MRI, we discuss the possible brain locations response to BIOCERAMIC Resonance that may be corresponding to the beneficial effects of relief of depression, sleep deprivation and other mental symptoms that associate with substance abuse and withdrawal effects. We suggest this could be potentially widely application on substances abuse., Graphical abstract Image 1

Increasing numbers of studies have demonstrated the existence of nanoplastics (1-999 nm) in the environment and commercial products, but the current technologies for detecting and quantifying nanoplastics are still developing. Herein, we present a combination of two techniques, e.g., scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), to analyze submicron-sized plastics. A drop-casting of a 20-nL particle suspension on a Piranha solution-cleaned silicon wafer with dry ice incubation and subsequent freeze-drying was used to suppress the coffee-ring effect. SEM images were used to quantify particles, and this technique is applicable for 0.195-1.04-μm polystyrene (PS), 0.311-μm polyethylene terephthalate (PET), and 0.344-μm polyethylene (PE) at a minimum concentration of 2.49 × 10

Photodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard treatment for peripheral lung tumor.. We previously proposed a novel light delivery method, in which lipiodol is perfused into the bronchial tree to increase the scope of illumination via the fiber effect. Herein, we attempted this novel technique under electromagnetic bronchoscope guidance in a hybrid operation room where lipiodol facilitated light diffusion, and evaluated the effectiveness and feasibility of this technique for peripheral lung cancers.This phase 0 pilot study included three patients with peripheral lung cancers (primary tumors ≤20-mm diameter). The photodynamic therapy was administered using Porfimer sodium as the photosensitizer, and an electromagnetic navigation bronchoscope in a hybrid operating room to guide the catheter to the tumor. This facilitated lipiodol infusion to encase the tumor and permit the transbronchial photodynamic therapy ablation.Administering 630 nm 200 J/cm (400mW/500sec) energy through a 3-cm cylindrical diffusing laser fiber was safe; no significant acute complications were observed. Although the treatment outcome was unsatisfactory due to the low light dose, tumor pathology in one case revealed tumor necrosis, with no significant damage to the surrounding lung tissue.Novel light delivery transbronchial photodynamic therapy ablation for peripheral lung tumors is feasible and safe. Additional clinical trials may help determine the best illumination plan and light dose through multiple deliveries from multiple angles.

Emerging adulthood is a unique and distinct period demographically, subjectively, and in terms of identity exploration in developed and developing countries. This study aimed to investigate emerging adults’ moral thinking and communication competencies, and their differences by socio-demographic factors (i.e., gender, religious affiliation, college major, educational stages), in Taiwan, the USA, and the UK, as well as compare similarities/common trends and diversities between the three groups. We modified and utilized the MTC-II scale, including two dilemma stories relating to an individual and societal moral dilemma, to assess 743 valid sample participants. We found that females in the Taiwan group scored highest on the MTC-II scale across the three samples, whereas religious affiliation differentiated the USA and the UK groups. We also noted differences in scores relating to the two stories and associated moral levels. These findings are interpreted as a foundation for future research and educational practice.

Elucidating the metabolic mechanism of gold nanoclusters (AuNCs) in bacteria will play a pivotal role in bacterial detection and inhibition. A facile method to investigate the metabolic mechanism o...

Global sea level rise due to an increasingly warmer climate has begun to induce hazards, adversely affecting the lives and properties of people residing in low-lying coastal regions and islands. Therefore, it is important to monitor and understand variations in coastal sea level covering offshore regions. Signal-to-noise ratio (SNR) data of Global Navigation Satellite System (GNSS) have been successfully used to robustly derive sea level heights (SLHs). In Taiwan, there are a number of continuously operating GNSS stations, not originally installed for sea level monitoring. They were established in harbors or near coastal regions for monitoring land motion. This study utilizes existing SNR data from three GNSS stations (Kaohsiung, Suao, and TaiCOAST) in Taiwan to compute SLHs with two methods, namely, Lomb–Scargle Periodogram (LSP)-only, and LSP aided with tidal harmonic analysis developed in this study. The results of both methods are compared with co-located or nearby tide gauge records. Due to the poor quality of SNR data, the worst accuracy of SLHs derived from traditional LSP-only method exceeds 1 m at the TaiCOAST station. With our procedure, the standard deviations (STDs) of difference between GNSS-derived SLHs and tide gauge records in Kaohsiung and Suao stations decreased to 10 cm and the results show excellent agreement with tide gauge derived relative sea level records, with STD of differences of 7 cm and correlation coefficient of 0.96. In addition, the absolute GNSS-R sea level trend in Kaohsiung during 2006–2011 agrees well with that derived from satellite altimetry. We conclude that the coastal GNSS stations in Taiwan have the potential of monitoring absolute coastal sea level change accurately when our proposed methodology is used.

Because robustness and accuracy of localization are crucial for autonomous driving applications. Using the conventional integration scheme of Inertial Navigation System (INS) and Global Navigation Satellite System (GNSS), pose estimation error can drift and accumulate with time, especially in GNSS challenging environment and in unknown environment where an existing map has not been constructed. In this paper, in term of using multi-sensor fusion for improving the positioning accuracy, we proposed a localization method that is based on LiDAR-based 3D Normal Distribution Transform (NDT) scan matching with an INS/GNSS integration scheme. As the experimental results, our proposed method showed a statistical improvement over the state of the art INS/GNSS integration scheme.

The Pacific island countries are particularly vulnerable to the effects of global warming including more frequent and intense natural disasters. Seawater inundation, one of the most serious disasters, could damage human property and life. Regional sea level rise, highest astronomic tide, vertical land motions, and extreme sea level could result in episodic, recurrent, or permanent coastal inundation. Therefore, assessing potential flooding areas is a critical task for coastal management plans. In this study, a simulation of the static flooding situation in the southwest coast of Taiwan (Tainan city) at the end of this century was conducted by using a combination of the Taiwan Digital Elevation Model (DEM), regional sea level changes reconstructed by tide gauge and altimetry data, vertical land deformation derived from leveling and GPS data, and ocean tide models. In addition, the extreme sea level situation, which typically results from high water on a spring tide and a storm surge, was also evaluated by the joint probability method using tide gauge records. To analyze the possible static flood risk and avoid overestimation of inundation areas, a region-based image segmentation method was employed in the estimated future topographic data to generate the flood risk map. In addition, an extreme sea level situation, which typically results from high water on a spring tide and a storm surge, was also evaluated by the joint probability method using tide gauge records. Results showed that the range of inundation depth around the Tainan area is 0–8 m with a mean value of 4 m. In addition, most of the inundation areas are agricultural land use (60% of total inundation area of Tainan), and two important international wetlands, 88.5% of Zengwun Estuary Wetlands and 99.5% of Sihcao Wetlands (the important Black-faced Spoonbills Refuge) will disappear under the combined situation. The risk assessment of flooding areas is potentially useful for coastal ocean and land management to develop appropriate adaptation policies for preventing disasters resulting from global climate change.

Oxidative stress, which is an early determinant of Alzheimer's disease (AD), is involved in mediating neuronal apoptosis in Aβ-induced cell death. C60 fullerenes are known to behave like a ”radical sponge” as they can sponge tip free radicals and act more effectively than other antioxidants. PEO-C60-3, a C60 fullerene derivative, was investigated against β-amyloid (Aβ)(subscript 25-35)-induced toxicity toward Neuro-2A cells in this study. PFG-C60-3 reduced Aβ(subscript 25-35)-induced cytotoxicity, which showed an increasing cell viability with C60 and Aβ(subscript 25-35) co-treated cells. Moreover, the intracellular reactive oxygen species (ROS) accumulation caused by Aβ-treated Neuro-2A cells was reduced by PEG-C60-3 co-treatment. Microarray for the analysis of gene expressions was investigated. Endoplasmic reticulum (ER) stress responsive genes, ion-channel, cell-cycle and anti-oxidant related cell responses were found to be associated with C60 protective mechanism against Aβ(subscript 25-35) treatment. The results offered new comprehension into the possible pathway of Aβ(subscript 25-35) gene expression and C60 protective mechanism. With the understanding of the roles of Aβ and C60 in cells, we can hopefully provide insight on therapeutic design using C60 fullerene nanoparticles against Aβ-associated diseases.

Rapid sea level rise, a severe consequence of global warming, could significantly damage the lives and properties of numerous human beings living in low-lying coastal areas. Therefore, realizing and monitoring coastal sea level variations are of great importance for human society. Conventionally, sea level heights are measured by using tide gauges; however, the records are contaminated by vertical land motions which are difficult to be separated. Recently, Global Navigation Satellite System Reflectometry (GNSS-R) technology has been proved to effectively monitor the coastal sea level changes from GNSS signal-to-noise ratio (SNR) data. However, the generation of detrended SNR ( SNR) depending on different satellite elevation angle intervals via a quadratic fitting, considerably influences the accuracy of sea level retrievals. Moreover, the quadratic fitting cannot perfectly describe the trend of SNR data. Therefore, we proposed a method combining ensemble empirical mode decomposition (EEMD) and ocean tide model to compute SLHs. EEMD can decompose the original SNR data into several intrinsic mode functions (IMFs) corresponding to specific frequencies. Then, Lomb-Scargle Periodogram (LSP) is applied to calculate the dominant frequency of the IMF with maximum spectral power. EEMD is not only suitable for dealing with nonlinear and nonstationary data but also eliminates the mode mixing problem of empirical mode decomposition (EMD) by adding white noises. In addition, we set an empirical SLH interval from ocean tide model as a quality control. In this study, the existing GNSS stations at the coasts of Taiwan are used to examine the proposed approach and then compare the results with those from the traditional quadratic fitting. Finally, the measurements from co-located or nearby traditional tide gauges are served as ground truth to evaluate the accuracy and stability of the mentioned methods.

Despite the great significance of precisely forecasting the wind speed for development of the new and clean energy technology and stable grid operators, the stochasticity of wind speed makes the prediction a complex and challenging task. For improving the security and economic performance of power grids, accurate short-term wind power forecasting is crucial. In this paper, a deep learning model (Long Short-term Memory (LSTM)) has been proposed for wind speed prediction. Knowing that wind speed time series is nonlinear stochastic, the mutual information (MI) approach was used to find the best subset from the data by maximizing the joint MI between subset and target output. To enhance the accuracy and reduce input characteristics and data uncertainties, rough set and interval type-2 fuzzy set theory are combined in the proposed deep learning model. Wind speed data from an international airport station in the southern coast of Iran Bandar-Abbas City was used as the original input dataset for the optimized deep learning model. Based on the statistical results, the rough set LSTM (RST-LSTM) model showed better prediction accuracy than fuzzy and original LSTM, as well as traditional neural networks, with the lowest error for training and testing datasets in different time horizons. The suggested model can support the optimization of the control approach and the smooth procedure of power system. The results confirm the superior capabilities of deep learning techniques for wind speed forecasting, which could also inspire new applications in meteorology assessment.

Voltage-gated CaV2.1 channels comprise a pore-forming α1Asubunit with auxiliary α2δ and β subunits. CaV2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding the CaV2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of CaV2.1 wild-type (WT) protein expression via aberrant proteasomal degradation. Here, we set out to delineate the protein degradation mechanism of human CaV2.1 subunit by identifying RNF138, an E3 ubiquitin ligase, as a novel CaV2.1-binding partner. In neurons, RNF138 and CaV2.1 coexist in the same protein complex and display notable subcellular colocalization at presynaptic and postsynaptic regions. Overexpression of RNF138 promotes polyubiquitination and accelerates protein turnover of CaV2.1. Disrupting endogenous RNF138 function with a mutant (RNF138-H36E) or shRNA infection significantly upregulates the CaV2.1 protein level and enhances CaV2.1 protein stability. Disrupting endogenous RNF138 function also effectively rescues the defective protein expression of EA2 mutants, as well as fully reversing EA2 mutant-induced excessive proteasomal degradation of CaV2.1 WT subunits. RNF138-H36E coexpression only partially restores the dominant-negative effect of EA2 mutants on CaV2.1 WT functional expression, which can be attributed to defective membrane trafficking of CaV2.1 WT in the presence of EA2 mutants. We propose that RNF138 plays a critical role in the homeostatic regulation of CaV2.1 protein level and functional expression and that RNF138 serves as the primary E3 ubiquitin ligase promoting EA2-associated aberrant degradation of human CaV2.1 subunits.SIGNIFICANCE STATEMENTLoss-of-function mutations in the human CaV2.1 subunit are linked to episodic ataxia type 2 (EA2), a dominantly inherited disease characterized by paroxysmal attacks of ataxia and nystagmus. EA2-causing mutants may exert dominant-negative effects on the CaV2.1 wild-type subunit via aberrant proteasomal degradation. The molecular nature of the CaV2.1 ubiquitin–proteasome degradation pathway is currently unknown. The present study reports the first identification of an E3 ubiquitin ligase for CaV2.1, RNF138. CaV2.1 protein stability is dynamically regulated by RNF138 and auxiliary α2δ and β subunits. We provide a proof of concept that protecting the human CaV2.1 subunit from excessive proteasomal degradation with specific interruption of endogenous RNF138 function may partially contribute to the future development of a novel therapeutic strategy for EA2 patients.

Rationale Sedation, dependence, and abuse liability limit the use of non-selective γ-aminobutyric acid (GABAA) receptor positive modulators for the treatment of anxiety. AZD7325 and AZD6280 are novel, subtype-selective GABAAα2,3 receptor positive modulators with limited sedative effects. Objectives The current study aimed to confirm target engagement at GABAA receptors by AZD7325 and AZD6280 in humans and to determine the relationship between exposure, GABAA receptor occupancy, and tolerability. Method Two PET studies, using high-resolution research tomography (HRRT) and the radioligand [11C]flumazenil, were performed in 12 subjects at baseline and after administration of single oral doses of AZD7325 (0.2 to 30 mg) and AZD6280 (5 to 40 mg). PET images were analyzed using a simplified reference tissue model, and regional binding potentials (BPND) were obtained. The relationship between plasma concentration of AZD7325 or AZD6280 and GABAA receptor occupancy was described by hyperbolic function, and K i,plasma (plasma concentration required for 50% receptor occupancy) was estimated. Assessments of safety and tolerability included recording of adverse events, vital signs, electrocardiogram, and laboratory tests. Results The [11C]flumazenil binding was reduced in a dose-dependent, saturable manner by both agents. Maximum receptor occupancy could be reached for both compounds without causing sedation or cognitive impairment. The K i,plasma estimates for AZD7325 and AZD6280 were 15 and 440 nmol/l, respectively. Conclusion High GABAA receptor occupancy by AZD7325 and AZD6280 could be reached without clear sedative effects. Electronic supplementary material The online version of this article (doi:10.1007/s00213-016-4506-4) contains supplementary material, which is available to authorized users.

Objective To report our experiences with 40 patients who were treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS) for uterine fibroids and their 6-month follow-up status. Materials and Methods A total of 40 patients with uterine fibroids underwent MRgFUS from January 2009 to November 2011. The Uterine Fibroid Symptoms and Quality of Life Questionnaire was used to determine the patients' Symptom Severity Scores (SSS) prior to and 6 months after treatment. The nonperfused volume (NPV) values and NPV ratio were obtained immediately at the end of the treatment and at 6 months follow-up. Results No procedure-related complications were noted throughout the 6-month follow-up period among the 40 patients who underwent MRgFUS for uterine fibroids. The mean reduction in SSS in our patients after 6 months was 43.7%, and the mean reduction of fibroid volume was 31.7%. In addition, the mean reduction of NPV and mean NPV ratio was 52.7% and 33.3%, respectively. Conclusion The results obtained from this study demonstrated that MRgFUS can be safely and effectively used to ablate uterine fibroids to produce a significant decrease in mean fibroid volume and improve SSS for up to 6 months after treatment.

Inflammation is the first step that leads to inflammatory cell migration, cytokine release, and myofibroblast formation. Myofibroblasts can deposit excess amounts of extracellular matrix. Cyclooxygenase (COX) inhibitor exhibits strong anti-inflammatory response; however, this is usually achieved with undesirable side effects. In this study, we demonstrated the effects of the fluorine-modified rutaecarpine (RUT), fluoro-2-methoxyrutaecarpine (F-RUT), in inflammatory damage in the lungs. Based on the results, F-RUT retained anti-inflammatory activity both in vitro and in vivo in lungs. Compared to the parent compound, F-RUT showed better COX-2 suppression as a COX-2-selective inhibitor with lower cytotoxicity, and enhanced molecular reactivity and biological activity. F-RUT was also observed to reduce reactive oxygen species (ROS) generation and inflammatory infiltrating neutrophils in lipopolysaccharide (LPS)-stimulated zebrafish and ovalbumin (OVA)/alum-challenged KLF-10-knockout mouse lungs, respectively. Furthermore, F-RUT ameliorated the respiratory function in OVA/alum-challenged BALB/c mice by maintaining the thickness of the blood-air barrier in mouse lungs. Overall, these data suggest that F-RUT may function as an effective therapeutic agent for inflammation-induced lung dysfunction, and a better selection for pharmaceutical purposes than conventionally used anti-inflammatory agents.

This chapter presents basic concepts in the key areas of alternate-fuel production for green aviation and provides a foundation for critical thinking. It outlines the international standards for jet fuel, along with a description of the most important physical characteristics for aviation fuel. The chapter provides fuel composition and its corresponding effects on fuel properties. The hydrocarbon composition of any particular tank of jet fuel is dependent on the properties of the crude oil, refining operations, and the use of additives. The emissions from an airplane are a function of fuel properties, the amount of fuel used, operating conditions, and the combustion efficiency. There are three commonly used categories of biofuels that indicate their readiness for commercialization. The categories are first-generation, second-generation, and third-generation biofuels. The chapter considers alternative fuel feedstocks, biorefining techniques, and an introduction to life cycle analysis for aviation fuel. Processes such as transesterification and hydroprocessing are used to transform the molecular structure of the crude oils.

本研究針對525 位學校教育人員、學生家長與民間團體代表進行全國性問卷調查，以瞭解其對於我國品德教育實施現況與問題及面臨十二年國教課程改革之看法。結果顯示：一、品德教育在各教育階段採多元但隨機方式實施，其中個人品德修養與團體規範的教育成效尚佳，但較缺乏公民意識與道德思辨能力之養成；二、品德教育實施之主要困難來自媒體與家庭負面影響，以及師生未予以積極重視；三、受試者對於應著重的品德核心價值與道德議題有所共識；四、單獨設科為多數教育人員與家長期望之品德課程模式；五、十二年國教品德教育須強化的配套措施含師資、教材、網路資源、行政支援與親職教育等。最後，根據分析結果，本研究提出相關的討論與初探性的建議。 A national survey of 525 educators, parents, and civic groups was conducted to determine their perception of the status quo of character and moral education in Grades 1 to 12 as well as their suggestions for the curriculum reform of 12-year basic education. The results indicate that (1) the implementation of character and moral education is diverse and nonsystematic, (2) negative influences of media and family and the ignorance of teachers and students are among the major difficulties in implementing moral and character education, (3) a consensus on the core values and moral issues that should be addressed in 12-year basic education has been attained, (4) most educators and parents prefer that character and moral education be taught as a timetabled subject, and (5) accompanying measures related to the implementation of 12-year basic education include teacher education, instructional materials, Internet resources, administrative support, and parent education. Finally, the results are discussed, and preliminary recommendations for character and moral education in 12-year basic education are proposed.

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound.

Modulating deposition of Aβ-containing plaques in the brain may be beneficial in treating Alzheimer's disease. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors have been shown to reduce Aβ in plasma and CSF in healthy volunteers. In this study safety, pharmacokinetics and pharmacodynamics that is reduction of the plasma biomarkers Aβ40 and Aβ42, of the BACE1 inhibitor AZD3839 were evaluated. Single oral ascending doses (1–300 mg) of AZD3839 were administered to 54 young healthy volunteers in a randomized, double-blind, placebo-controlled study. The data was analyzed using non-linear mixed effects modeling. AZD3839 reduced Aβ40 and Aβ42 in plasma with estimated potencies (EC50) of 46 and 59 nM, respectively, and a maximum effect of approximately 55%. This was in excellent agreement with the concentration–response relationships obtained in mouse and guinea pig. AZD3839 exposure displayed non-linear kinetics, described by a three-compartment model with a saturated binding compartment and an increase in bioavailability with dose. AZD3839 was safe, although, a dose-dependent QTcF prolongation was observed (mean 20 milliseconds at 300 mg). In conclusion, AZD3839 reduced plasma Aβ40 and Aβ42, demonstrating clinical peripheral proof of mechanism. Pre-clinical models were predictive for the effect of AZD3839 on the human plasma biomarker in a strictly quantitative manner.

Background: Galectin-3 (Gal-3) shows the ability of survival prediction in heart failure (HF) patients. However, Gal-3 is strongly associated with serum markers of cardiac extracellular matrix (ECM) turnover. The aim of this study is to compare the impact of Gal-3 and serum markers of cardiac ECM turnover on prognostic prediction of chronic systolic HF patients. Methods: Serum Gal-3, brain natriuretic peptide (BNP), extracellular matrix including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2, 9 (MMP-2, 9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. Cox regression analysis was used for survival analysis. Results: A total of 105 (81 male) patients were enrolled. During 980±346 days follow-up, 17 patients died and 36 episodes of HF admission happened. Mortality of these patients was significantly associated with the log PIIINP (β= 15.380; P=0.042), log TIMP-1(β= 44.530; P=0.003), log MMP-2 (β= 554.336; P

// Yen-Tin Lin 1,* , Yen-Hung Lin 2,5,* , Xue-Ming Wu 1 , Chi-Lun Ko 3 , Ruoh-Fang Yen 3 , Ying-Hsein Chen 2 , Ron-Bin Hsu 4 , Chi-Ming Lee 2 , Shoei-Shen Wang 4 , Ming-Fong Chen 2,6 and Yen-Wen Wu 2,3,7,8 1 Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 3 Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 4 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 5 Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA 6 Cardiovascular Research Laboratory, Cardiovascular Center, Clinical Outcome Research and Training Center, Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan 7 Cardiology Division of Cardiovascular Medical Center, Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan 8 National Yang-Ming University School of Medicine, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Yen-Wen Wu, email: // Keywords : fibrosis; restrictive filling; ventriculography Received : October 04, 2016 Accepted : November 24, 2016 Published : December 04, 2016 Abstract Myocardial fibrosis leads to a restrictive diastolic filling pattern of the left ventricle which is associated with a poor prognosis in patients with heart failure. We investigated the relationship between cardiac fibrosis and restrictive filling pattern of the left ventricle measured by Tc99m left ventriculography in patients with chronic symptomatic heart failure. Serum cardiac extracellular matrix markers including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2,9 (MMP-2,9), and tissue inhibitor of MMP-1 (TIMP-1) were analyzed. Fifty-one (39 males) patients were enrolled. Their median age was 51.8 years, and median left ventricular ejection fraction was 31.9%. Time to peak filling rate of the left ventricle was significantly correlated with serum levels of the three cardiac extracellular matrix markers (TIMP-1, PIIINP, and MMP-2). The patients with a restrictive diastolic filling pattern of the left ventricle (time to peak filling rate ≤ 154 ms) had significantly higher levels of these extracellular matrix markers. In receiver operating characteristic curve analysis, areas under the curve of PIIINP, TIMP-1, and MMP-2 were 0.758, 0.695, and 0.751 to predict the presence of a restrictive pattern. In C -statistics, all three cardiac extracellular matrix markers significantly increased the area under the curve after adding creatinine. In net reclassification improvement and integrated discrimination improvement models, PIIINP and MMP-2 significantly improved the predictive power of age, creatinine and brain natriuretic peptide. In conclusion, serum extracellular matrix markers are significantly correlated with restrictive diastolic filling pattern of the left ventricle in patients with heart failure.

Voltage-gated Ca(V)2.1 channels comprise a pore-forming α(1A) subunit with auxiliary α(2)δ and β subunits. Ca(V)2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding the Ca(V)2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of Ca(V)2.1 wild-type (WT) protein expression via aberrant proteasomal degradation. Here, we set out to delineate the protein degradation mechanism of human Ca(V)2.1 subunit by identifying RNF138, an E3 ubiquitin ligase, as a novel Ca(V)2.1-binding partner. In neurons, RNF138 and Ca(V)2.1 coexist in the same protein complex and display notable subcellular colocalization at presynaptic and postsynaptic regions. Overexpression of RNF138 promotes polyubiquitination and accelerates protein turnover of Ca(V)2.1. Disrupting endogenous RNF138 function with a mutant (RNF138-H36E) or shRNA infection significantly upregulates the Ca(V)2.1 protein level and enhances Ca(V)2.1 protein stability. Disrupting endogenous RNF138 function also effectively rescues the defective protein expression of EA2 mutants, as well as fully reversing EA2 mutant-induced excessive proteasomal degradation of Ca(V)2.1 WT subunits. RNF138-H36E coexpression only partially restores the dominant-negative effect of EA2 mutants on Ca(V)2.1 WT functional expression, which can be attributed to defective membrane trafficking of Ca(V)2.1 WT in the presence of EA2 mutants. We propose that RNF138 plays a critical role in the homeostatic regulation of Ca(V)2.1 protein level and functional expression and that RNF138 serves as the primary E3 ubiquitin ligase promoting EA2-associated aberrant degradation of human Ca(V)2.1 subunits. SIGNIFICANCE STATEMENT Loss-of-function mutations in the human Ca(V)2.1 subunit are linked to episodic ataxia type 2 (EA2), a dominantly inherited disease characterized by paroxysmal attacks of ataxia and nystagmus. EA2-causing mutants may exert dominant-negative effects on the Ca(V)2.1 wild-type subunit via aberrant proteasomal degradation. The molecular nature of the Ca(V)2.1 ubiquitin–proteasome degradation pathway is currently unknown. The present study reports the first identification of an E3 ubiquitin ligase for Ca(V)2.1, RNF138. Ca(V)2.1 protein stability is dynamically regulated by RNF138 and auxiliary α(2)δ and β subunits. We provide a proof of concept that protecting the human Ca(V)2.1 subunit from excessive proteasomal degradation with specific interruption of endogenous RNF138 function may partially contribute to the future development of a novel therapeutic strategy for EA2 patients.

The evolution of wireless communication protocols drives the quest of power-efficient and flexible computing for embedded DSPs, but popular architectures, very-long-instruction-word (VLIW) and application-specific instruction set processor (ASIP), serve as opposite extreme cases in regard to power-efficiency and flexibility. To this end, we present DeAr: Dual-thread Architecture DSP, which manipulates a multi-banked register file that enables simultaneous multi-threading (SMT), and a transport-triggered bus that exploits the data forwarding mechanism in its compact datapath. We also propose a novel scheduling algorithm which leverages the compact hardware to achieve both high throughput and flexible computation. In the experiment of common DSP kernels, DeAr saves 20.3%–13.1% and 31.8%–2.2% of power dissipation, 36.1%–31.5% and 28.2%–5.7% of area, compared with VLIW and ASIP respectively.

Previous biomolecular and animal studies have shown that a room-temperature far-infrared-rayemitting ceramic material (bioceramic) demonstrates physical-biological effects, including the normalization of psychologically induced stress-conditioned elevated heart rate in animals. In this clinical study, the Harvard step test, the resting metabolic rate (RMR) assessment and the treadmill running test were conducted to evaluate possible physiological effects of the bioceramic material in human patients. The analysis of heart rate variability (HRV) during the Harvard step test indicated that the bioceramic material significantly increased the high-frequency (HF) power spectrum. In addition, the results of RMR analysis suggest that the bioceramic material reduced oxygen consumption (VO2). Our results demonstrate that the bioceramic material has the tendency to stimulate parasympathetic responses, which may reduce resting energy expenditure and improve cardiorespiratory recovery following exercise.

Introduction Recent advances in the treatment of NSCLC highlight the importance of distinguishing NSCLC subtypes and genotypes. We aimed to determine whether histological specimens obtained from computed tomography (CT)-guided biopsy are suitable for specific subtyping and epidermal growth factor receptor ( EGFR ) analyses of NSCLC. Patients and Methods The clinicohistological data of 332 consecutive patients undergoing 352 CT-guided biopsies for lung lesions between January 2007 and December 2011 were retrospectively analyzed. Additionally, NSCLC specimens were examined for the suitability of EGFR mutational testing. Results Of 209 specimens diagnosed as NSCLC, 197 (94.3%) were specifically subtyped into adenocarcinoma (n = 164; 78.5%), squamous cell carcinoma (n = 27; 12.9%) and other subtypes (n = 6; 2.9%). The rate of NSCLC not otherwise specified (NOS) was 5.7%, and the diagnosis of NSCLC-NOS was significantly associated with the poor differentiation of cancer (adjusted odds ratio, 6.17; 95% confidence interval, 1.62-23.55; P = .008). Of 134 histological tumor specimens submitted for EGFR molecular testing, 132 (98.5%) were suitable for analyses, and 130 of them (98.5%) showed conclusive results, revealing 59.8% (n = 79) with EGFR exon mutation(s). The sensitivity, specificity, and positive and negative predictive values of CT-guided biopsy in patients with malignancy were 92.2%, 100%, 100%, and 74.1%, respectively. Six percent (n = 21) of total lung biopsies led to pneumothorax requiring chest drainage, and no procedure-related fatality was observed. Conclusion Small tumor specimens obtained with CT-guided needle lung biopsy are suitable for specific subtyping and EGFR analyses of NSCLC, thus providing critical information for personalized therapy.