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The propagation of the hepatitis C virus (HCV) is regulated in part by the phosphorylation of its nonstructural protein NS5A that undergoes sequential phosphorylation on several highly conserved serine residues and switches from a hypo- to a hyperphosphorylated state. Previous studies have shown that NS5A sequential phosphorylation requires NS3 encoded on the same NS3-NS4A-NS4B-NS5A polyprotein. Subtle mutations in NS3 without affecting its protease activity could affect NS5A phosphorylation. Given the ATPase domain in the NS3 COOH terminus, we tested whether NS3 participates in NS5A phosphorylation similarly to the nucleoside diphosphate kinase-like activity of the rotavirus NSP2 nucleoside triphosphatase (NTPase). Mutations in the NS3 ATP-binding motifs blunted NS5A hyperphosphorylation and phosphorylation at serines 225, 232, and 235, whereas a mutation in the RNA-binding domain did not. The phosphorylation events were not rescued with wild-type NS3 provided in trans. When provided with an NS3 ATPase-compatible ATP analog, N(6)-benzyl-ATP-γ-S, thiophosphorylated NS5A was detected in the cells expressing the wild-type NS3-NS5B polyprotein. The thiophosphorylation level was lower in the cells expressing NS3-NS5B with a mutation in the NS3 ATP-binding domain. In vitro assays with a synthetic peptide and purified wild-type NS3 followed by dot blotting and mass spectrometry found weak NS5A phosphorylation at serines 222 and 225 that was sensitive to an inhibitor of casein kinase Iα but not helicase. When casein kinase Iα was included in the assay, much stronger phosphorylation was observed at serines 225, 232, and 235. We concluded that NS5A sequential phosphorylation requires the ATP-binding domain of the NS3 helicase and that casein kinase Iα is a potent NS5A kinase. IMPORTANCE For more than 20 years, NS3 was known to participate in NS5A sequential phosphorylation. In the present study, we show for the first time that the ATP-binding domain of NS3 is involved in NS5A phosphorylation. In vitro assays showed that casein kinase Iα is a very potent kinase responsible for NS5A phosphorylation at serines 225, 232, and 235. Our data suggest that ATP binding by NS3 probably results in conformational changes that recruit casein kinase Iα to phosphorylate NS5A, initially at S225 and subsequently at S232 and S235. Our discovery reveals intricate requirements of the structural integrity of NS3 for NS5A hyperphosphorylation and HCV replication.

A toilet set with UVC LEDs radiating 275 nm for sterilization is presented. A visible indication and a proximity detection to warn and protect users from being hurt by the UVC radiation are also included. The sterilization of the toilet seat begins whenever the toilet lid lays down well on the seat. The condition is detected and confirmed by a coordination of a reed switch and a power magnet. The sterilization will last for an expected time, six minutes in a prototype toilet set. If it is interrupted, the proposed safety measures will take over the operation of the sterilization.

Jen-Yang Tang,1,2Tzu-Jung Yu,3 Li-Ching Lin,4–6 Sheng-Yao Peng,3 Chun-Lin Wang,7 Fu Ou-Yang,8,9Yuan-Bin Cheng,10 Hsueh-Wei Chang9,11–131Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 2Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 4Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan; 5School of Medicine, Taipei Medical University, Taipei 11031, Taiwan; 6Department of Optometry, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan; 7Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 30062, Taiwan; 8Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; 9Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; 10Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 11Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; 12Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 13Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanIntroduction: The genus Nepenthes of the pitcher plants contains several natural and hybrid species that are commonly used in herbal medicine in several countries, but its possible use in cancer applications remains unknown as yet.Methods: In this study, we investigated the antioral cancer properties using ethyl acetate extracts of the Nepenthes hybrid (Nepenthes ventricosa x sibuyanensis), namely EANS. The bioactivity was detected by a MTS-based cell proliferation assay and flow cytometric or Western blot analysis for apoptosis, oxidative stress, and DNA damage.Results: Treatment for 24 hrs of EANS inhibited all three types of oral cancer cells that were tested (Ca9-22, CAL 27, and SCC9), with just a small difference to normal oral cells (HGF-1). This antiproliferation was inhibited by pretreatments with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC), and the apoptosis inhibitor (Z-VAD). EANS treatment increased the subG1 population and it also dose- and time-dependently induced annexin V- and pancaspase-detected apoptosis as well as cleaved caspases 3 and 9 overexpressions in the oral cancer cells (Ca9-22). After EANS treatment of Ca9-22 cells, intracellular ROS and mitochondrial superoxide (MitoSOX) were overexpressed and mitochondrial membrane potential (MMP) was disrupted. Moreover, DNA damages such as γH2AX and 8-oxo-2ʹ-deoxyguanosine (8-oxodG) were increased after EANS treatment to Ca9-22 cells. The EANS-induced effects (namely, oxidative stress, apoptosis, and DNA damage) were suppressed by ROS scavenger.Conclusion: Our findings demonstrated that EANS inhibits ROS-mediated proliferation against oral cancer cells.Keywords: Nepenthes, oral cancer, oxidative stress, apoptosis, DNA damage

Developing visible-light communication (VLC) with easy-to-use circuit modules in order to be integrated with consumer electronics could facilitate VLC technology adopted in more wireless applications for home. The study first implements functions of lighting for reading and data transmitting with a white organic light-emitting diode (OLED) panel. A method to keep the two functions implemented on the same lighting panel from interfering with each other is proposed and investigated. For data transmission, an optical receiver working with the OLED-based data transmitter to organize an optical channel is also proposed with a cost-effective approach based on a mature infrared receiver module. Under the recommended illuminance of 500 lux for reading and office work, home devices can receive codes in 2404 bps with the low-cost and convenient optical channel.

A convenient and economical optical channel for wireless control in the space for residents is carried out with the beam from light-emitting diodes (LEDs) while they are working for illumination. In theory, optical wireless technology can be implemented with lower cost and consumes lower power than those done by radio. However, optical communication is usually found applied in infrared. In the study, the white light of a LED lamp with the intensity for home illumination is considered to build an optical channel for wireless control of home devices. To be convenient and economical, the mature infrared technology is employed. Although data bits can only move within the channel in 2500 bps at most, the hardware to receive them is compact and cheap enough to be included in consumer electronics.

This study optimizes the lighting of 38 LED chips connected in series with 14 switches to bypass parts of them according to the alternating voltage level across the LED string. Furthermore, the illumination produced by the light will not become unstable while the light is used as binary signals at the same time, to transmit data by controlling another switch.

Although the amount of cooking fumes can be estimated based on the output of the piezoelectric transducer, a proper translation from the response of the transducer to the exhaust rate remains to be implemented. In this paper, a smart translation method is used to generate a ventilating signal for the release of cooking fumes based on the output of a piezoelectric transducer. The start and end states of the fume release were computed according to the temporal variation of the output of the piezoelectric transducer, as determined with four successive samples. These detected states were mapped to a 1-bit digital ventilating signal, which then controlled the exhaust fan. Results from a demonstrated range hood system showed that the proposed method enhances the detection of cooking fumes and provides an effective control of the exhaust fan

Ammad Ahmad Farooqi,1 Jen-Yang Tang,2–4 Ruei-Nian Li,5 Muhammad Ismail,1 Yung-Ting Chang,6 Chih-Wen Shu,7 Shyng-Shiou F Yuan,8,9 Jing-Ru Liu,5 Qaisar Mansoor,1 Chih-Jen Huang,2,3,* Hsueh-Wei Chang5,9–11,*1Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital, Islamabad, Pakistan, 2Department of Radiation Oncology, Faculty of Medicine, College of Medicine, 3Department of Radiation Oncology, Kaohsiung Medical University Hospital, 4Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, 5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, 7Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 8Translational Research Center, 9Cancer Center, Kaohsiung Medical University Hospital, 10Institute of Medical Science and Technology, National Sun Yat-sen University, 11Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan*These authors contributed equally to this workAbstract: Research concerning the epigenome over the years has systematically and sequentially shown substantial development and we have moved from global inhibition of modifications of the epigenome toward identification and targeted therapy against tumor-specific epigenetic mechanisms. In accordance with this approach, several drugs with epigenetically modulating activity have received considerable attention and appreciation, and recently emerging scientific evidence is uncovering details of their mode of action. High-throughput technologies have considerably improved our existing understanding of tumor suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In this review, we summarize the general epigenetic mechanisms in cancer, including: the post-translational modification of DNA methyltransferase and its mediated inactivation of Ras association domain family 1 isoform A, Sonic hedgehog signaling, Wnt signaling, Notch signaling, transforming growth factor signaling, and natural products with epigenetic modification ability. Moreover, we introduce the importance of nanomedicine for delivery of natural products with modulating ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive knowledge regarding epigenetic dysregulation will be helpful in the upcoming era of molecular genomic pathology for both detection and treatment of cancer. Epigenetic information will also be helpful when nanotherapy is used for epigenetic modification.Keywords: epigenetic, modification, methylation, natural products, cancer

Opening windows is frequently done to refresh the indoor air for the occupants. To maintain the cleanliness and freshness of the indoor air, more outdoor air is needed. But its high temperature and humidity are harmful to the thermal comfort of the indoor environment. Therefore, determining the amount of outdoor air allowed to enter the room is very important for the optimum conditioning of the indoor air. The ASHRAE comfort charts indicate the percentage of subjects feeling comfortable during various combinations of dry-bulb temperature, humidity, and air movement. A set of mathematical expressions were proposed to model the charts in order to calculate the comfort degree of the outdoor air automatically with its temperature and humidity. In this paper, the measurement of temperature and humidity was completed by a self-developed digital method. Besides, the comfort level of the sampled air was also simultaneously determined by this digital method based on the mathematical model of comfort charts. The system implemented based on our method is portable. This will let us make good use of the outdoor air and controll the ventilation machine more effectively.

The exhaust fan in a kitchen range hood is required to generate an adequate suction flow to eliminate the especially high levels of cooking contaminants in Chinese kitchens. Reducing the range hood noise and its power consumption down to an acceptable level is an important issue. In this paper, a low-cost smart range hood system is proposed. A sensitive piezoelectric transducer senses the level of the cooking contaminants and the output regulates the speed of the exhaust fan. Under several cooking conditions, the speed of the exhaust fan, its noise level, and the power consumption were examined. Results showed that the noise level and power consumption can be markedly reduced with the transducer and the control circuit. The average noise level is 65.66 dB and the power consumption 123.97 W, both lower than those of the conventional range hood system, which are 72 dB and 216 W, respectively.

Alternative splicing is a major diversification mechanism in the human transcriptome and proteome. Several diseases, including cancers, have been associated with dysregulation of alternative splicing. Thus, correcting alternative splicing may restore normal cell physiology in patients with these diseases. This paper summarizes several alternative splicing-related diseases, including cancers and their target genes. Since new cancer drugs often target spliceosomes, several clinical drugs and natural products or their synthesized derivatives were analyzed to determine their effects on alternative splicing. Other agents known to have modulating effects on alternative splicing during therapeutic treatment of cancer are also discussed. Several commonly used bioinformatics resources are also summarized.

Long noncoding RNA (lncRNA) function is described in terms of related gene expressions, diseases, and cancers as well as their polymorphisms. Potential modulators of lncRNA function, including clinical drugs, natural products, and derivatives, are discussed, and bioinformatic resources are summarized. The improving knowledge of the lncRNA regulatory network has implications not only in gene expression, diseases, and cancers, but also in the development of lncRNA-based pharmacology.

RNA editing is vital to provide the RNA and protein complexity to regulate the gene expression. Correct RNA editing maintains the cell function and organism development. Imbalance of the RNA editing machinery may lead to diseases and cancers. Recently, RNA editing has been recognized as a target for drug discovery although few studies targeting RNA editing for disease and cancer therapy were reported in the field of natural products. Therefore, RNA editing may be a potential target for therapeutic natural products. In this review, we provide a literature overview of the biological functions of RNA editing on gene expression, diseases, cancers, and drugs. The bioinformatics resources of RNA editing were also summarized.

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders.

Owing to AC LED can be driven directly without any AC to DC converter, the volume and the cost of AC LED can be reduced. Avoiding the power conversion loss, AC LED can have lower energy consumption and higher luminous efficiency than DC LED does. Because of high brightness, low power consumption and long lifetime, LED has been used as a lighting device and is expected to replace the high power-consuming incandescent and fluorescent lamps in the 21th century, in consequence the white light AC LED is a better choice for general illumination in the future. In this study, a white light AC LED smart lighting system equipped with visible light time-division multiplexing optical communication for free space is proposed. In the system, the timing to transmit data is synchronized with the period of the AC power on the wall, in order to keep the transmitted optical signal in an enough level. As a result, the time-division multiplexing optical communication by AC LED lighting is achieved.

The work attempts to reduce the power consumption of a personal computer (PC)-based server of an Internet-based data acquisition system using a novel server agent. An Internet-based data acquisition system requires at least one PC as the central server. The system needs to be run for a long time. If few data are transferred, the server stays at an almost idle state. However, keeping the server running without doing anything wastes power. Reducing this unnecessary power consumption by a PC-based server and further reducing the power consumption of an entire system are the goals of this work. This work is based on a microcontroller-based device. The novel microcontroller-based device in this work is called a Server Agent. This agent receives data from clients while the original PC-based server is off. After the amount of data transferred exceeds a certain limit, the Server Agent powers on the PC-based server and dumps the data to the PC-based server. The Server Agent will power off the PC-based server again once all data are dumped. The power consumed by the Server Agent is

Aim. The aim of this study was to compare the effect of protocol-directed sedation propofol vs. midazolam by nurses in intensive care on efficacy, haemodynamic stability and patient satisfaction. Background. Protocols represent one method potentially to reduce treatment delays and ensure that medical care is administered in a standardised manner. Propofol and midazolam are often used for sedation in intensive care units. Method. A randomised, prospective cohort study and data were collected in 2003. The subjects were randomised either into propofol (n = 32) or into midazolam (n = 28) group. Efficacy of sedation, haemodynamic stability, pulse oximetry saturation, Acute Physiology and Chronic Health Evaluation II (APACHE II score), weaning time from mechanical ventilation, duration of mechanical ventilation, length of stay at intensive care unit, sedative drugs cost and patient satisfaction were measured. Results. The nursing staff were able to maintain patients at Ramsay sedation scale (RSS) 3–4 during the sedative period. The efficacy of sedation was 74·2% and 66·9% of time in propofol and midazolam group respectively. Both sedatives reduced the arterial blood pressure and heart rate, but did not alter haemodynamic stability. The mean score of satisfactory sedation was not significantly different between the two groups (propofol: 11·4 SEM 0·2 vs. midazolam: 11·5 SEM 0·7). Conclusion. Protocol-directed sedation with propofol vs. midazolam by nurses were similar in quality during the sedative period. Relevance to clinical practice. This sedation practice for titration of propofol and midazolam by nurses was of similar quality and able to achieve an appropriate depth of sedation during the sedative period. Furthermore, they should provide care for patients’ needs during the sedative period.

In this paper exact distribution of Bartlett's statistic for testing equality of variances for Gaussian models is derived for equal as well as unequal sample sizes. Percentage points have also been tabulated for an equivalent test statistic.