Cardiac PI3Kα Signaling and K+ Channel Regulation in Cardiac Hypertrophy and Heart Failure

Pathologic biomechanical stresses cause cardiac hypertrophy, which is associated with QT prolongation and increased risk of life-threatening ventricular arrhythmias. Previous studies demonstrated that repolarizing K+ current densities are decreased in pressure overload-induced left ventricular hypertrophy, resulting in action potential and QT prolongation. Cardiac hypertrophy also occurs with exercise training, but this physiological hypertrophy is not associated with electrical abnormalities or increased arrhythmia risk, suggesting that repolarizing K+ currents are upregulated, in parallel with the increase in myocyte size, to maintain normal cardiac function. To explore this hypothesis directly, two mouse models of physiological hypertrophy, one produced by chronic exercise: swim-) training of wild type mice and the other by cardiac-specific expression of constitutively active phosphoinositide-3-kinase-p110α: caPI3Kα), were utilized. Electrophysiological experiments revealed that repolarizing K+ current amplitudes were increased and K+ current densities were normalized in hypertrophied ventricular myocytes from swim-trained or caPI3Kα animals. Molecular analyses revealed that increases in K+currents reflect the upregulation of the transcripts encoding the underlying K+ channel subunits. Importantly, additional experiments demonstrated that the transcriptional upregulation of myocardial K+ channel expression in response to exercise or augmented PI3Kα signaling is independent of cellular hypertrophy and Akt signaling. The hypothesis that increased PI3Kα signaling can counteract the adverse electrophysiological remodeling, including decreased K+ current densities and impaired repolarization associated with pathological hypertrophy and heart failure was also explored. These experiments revealed that increased PI3Kα signaling, but not renin-angiotensin system blockade, results in transcriptional upregulation of repolarizing K+ channel subunits and normalization of K+ current densities in transverse aortic constriction: TAC)-induced pathological hypertrophy, as well as in a transgenic mouse model of dilated cardiomyopathy/heart failure. Increased PI3Kα signaling, therefore, normalizes ventricular action potential durations, QT intervals and cardiac electrical functioning in the hypertrophied and failing heart. Additional studies here applied a combined miRNA- and RNA-sequencing approach to define the impact of enhanced PI3Kα signaling on myocardial transcriptome structure in the setting of pressure overload-induced pathological left ventricular hypertrophy. These analyses revealed that enhanced PI3Kα signaling normalized miRNAs and mRNAs that were aberrantly expressed in pathological hypertrophy and that increased PI3Kα signaling reduces cardiac fibrosis in pathological hypertrophy through the modulation of TGF-β signaling and miR-21 expression. In conclusion, enhanced PI3Kα signaling results in the transcriptional upregulation of K+ channel subunits and the maintenance of cardiac excitability in physiological hypertrophy, and the impact of increased PI3Kα signaling on K+ channel regulation is independent of cellular hypertrophy and Akt. In addition, enhancing PI3Kα signaling increases repolarizing K+ currents and K+ channel subunit expression in mouse models of pathological hypertrophy and heart failure, ameliorating arrhythmogenic electrical remodeling. Augmentation of PI3Kα signaling, therefore, may be a useful and unique strategy to protect against the increased risk of ventricular arrhythmias and sudden death associated with cardiomyopathy. The results here also demonstrate the power and robustness of next-generation sequencing in efforts to define the cardiac transcriptome architecture and dynamics in physiological and pathological contexts, as well as to identify novel molecular mechanisms important in cardiovascular pathophysiology

Factors Influencing the Usage of Mobile Value-Added Services

Mobile value-added services have drawn the attention of researchers and practitioners recently, due to the rapid development of the mobile telecommunications market. Various mobile-based services and applications have therefore been introduced in order to satisfy mobile phone subscribers’ needs. Facing intensive competition, service providers are eager to persuade mobile phone subscribers into using the mobile value-add services in the hope to expand market share and ultimately raise revenues. This study therefore intends to investigate the factors that influence mobile phone subscribers’ intention to use mobile value-added services in Taiwan by incorporating quality factors and perceived playfulness with the Technology Acceptance Model. A preliminary proposal is presented in this extended abstract, together with expected contributions for research and practice

The Adoption of Wikipedia: A Community- and Information Quality-Based View

The Web 2.0 model has aroused vast attention as it alters the traditional role of Internet users as pure information receivers. Wikipedia, as one of the most successful case of the Web 2.0 model, creates an online encyclopedia through the collective efforts of volunteers. Shared freely by all Internet users, it forms an online community platform on which users can seek and share knowledge. This study investigates the factors that affect the adoption of Wikipedia. Based on the TAM of Davis (1989), perceived critical mass, community identification, and perceived information quality were incorporated into the research model to explain the intention and usage of Wikipedia. This research is a work-in-progress and a questionnaire survey will be executed, targeting at Internet users who had prior experiences with knowledge seeking on Wikipedia

The Different Attribute of Online Store- An Industrial Perspective

Online stores are dramatically increasing and becoming popular, in a way that enterprisers invest tremendous resource and effort to meet customer requirements. However, the failure rate resulting from improper operation has been increasing year by year. By investigating the main cause, the operators cannot grasp the online store websites’ industry type and attribute category. Therefore, they fail to effectively use resource, show website image of the stores and information quality, to further meet customers’ demand and obtain the expected operational efficiency. Therefore, this research (1) grasps the website attribute of online stores by reviewing the literature; (2) sets up “online store website attributes structure” through qualitative method, serving as a basis for enterprisers to improve the operation/service mechanism; (3) sets up “industry breadth and depth graph”, so as to find the website content equilibrium degree of various industries’ online store and further obtain improvement strategy. It is believed that this research result, as said by the professors and scholars being interviewed, not only assists enterprisers to clearly grasp advantage/disadvantage and strategy of online store website attribute, but also promotes the effectiveness in resource utilization and the probability of success. Meanwhile, this research result can also effectively link practical application and academic value and provide researchers with new direction and scope.DOR : 98.1000/1726-8125.2015.0.27.0.0.84.10

Low temperature and high magnetic field spectroscopic ellipsometry system

We report on the design and implementation of a spectral ellipsometer at near-infrared wavelength (700-1000 nm) for samples placed in high magnetic fields (up to 14 T) at low temperatures (~4.2 K). The main optical components are integrated in a probe, which can be inserted into a conventional long-neck He dewar and has a very long free-space optical path (~1.8 m×2). A polarizer-sample-(quarter-wave plate)-rotating analyzer configuration was employed. Two dielectric mirrors, one before and one after the sample in the optical path, helped to reflect the light back to the analyzer and a two-axis piezo-driven goniometer under the sample holder was used to control the direction of the reflected light. Functional test results performed on an intrinsic GaAs wafer and analysis on the random error of the system are shown. We obtained both amplitude and phase ellipsometric spectra simultaneously and observed helicity transformation at energies near the GaAs exciton transitions in the phase spectra. Significant shifts of them induced by magnetic fields were observed and fitted with a simple model. This system will allow us to study the collective magneto-optical response of materials and spatial dispersive exciton-polariton related problems in high external magnetic fields at low temperatures

Dedifferentiated liposarcoma can induce a leukemoid reaction

SummaryLiposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence

Frequency-based Vehicle Idling Detection

Continuous increases in fuel prices and environmental awareness have raised the importance of reducing vehicle emissions, with many national governments passing anti-idling laws. To reduce air pollution and fuel consumption, we propose a frequency-based vehicle idling detection method to remind drivers to turn off the engine vehicle idling exceeds a certain time threshold. The method is implemented in existing handheld devices without any modification to the car or engine, making the solution cheap and simple to implement in any type of motor vehicle. Experimental results show the proposed method can effectively differentiate idling, engine-off, and moving conditions. Two implementation cases are presented to demonstrate the feasibility and performance of the proposed method