Quantification of Outdoor Tobacco Smoke Exposure at Outdoor Smoking Facilities.

INTRODUCTION: The implementation of indoor smoke-free policy has compelled smokers to go outdoors to smoke. Outdoor smoking facilities were installed to designate outdoor smoking area. The purposes of the study were to identify factors of outdoor tobacco smoke (OTS) around open type outdoor smoking facility and to compare the OTS exposure by the type of outdoor smoking facility. METHODS: Outdoor concentrations of particulate matter smaller than 2.5 µm in aerodynamic diameter (PM2.5) were measured at 3 different distances (0, 1, and 3 m) from the entrance of the open-type outdoor smoking facility with a simulated smoking source. For field measurements, PM2.5 concentrations of inside and outside of 33 operating outdoor smoking facilities were simultaneously measured for 30 min. RESULTS: For the smoking simulation, the outside PM2.5 concentrations and the peak occurrence rates increased significantly as the number of cigarettes smoked increased, the distance from the entrance decreased, and the wind speed increased (p < .0001). For the field measurement, the inside PM2.5 concentration of the outdoor smoking facilities varied significantly by types of the outdoor smoking facility (p = 0.022). The outside PM2.5 concentrations were not significantly different by types of outdoor smoking facility. CONCLUSIONS: OTS in an open type outdoor smoking facility were detected at 3 m away from the entrance of the smoking facility. Outdoor smoking facility should have a buffer zone to reduce OTS exposure of pedestrians. Many smokers were observed outside of the outdoor smoking facility not inside. Management and education of smokers to smoke inside the facility is needed. IMPLICATIONS: The study showed the effects of the outdoor smoking facility. Outdoor smoking facility should be installed with a sufficient buffer zone. Closed or semi-enclosed outdoor smoking facilities should not be installed. It could be used as a base data to set an outdoor smoking area on the populated area such as the city center and to establish an installation location of an outdoor smoking facility in the designated outdoor smoking area.

A Single-Chip 64-Channel Ultrasound RX-Beamformer Including Analog Front-End and an LUT for Non-Uniform ADC-Sample-Clock Generation.

A 64-channel RX digital beamformer was implemented in a single chip for 3-D ultrasound medical imaging using 2-D phased-array transducers. The RX beamformer chip includes 64 analog front-end branches including 64 non-uniform sampling ADCs, a FIFO/Adder, and an on-chip look-up table (LUT). The LUT stores the information on the rising edge timing of the non-uniform ADC sampling clocks. To include the LUT inside the beamformer chip, the LUT size was reduced by around 240 times by approximating an ADC-sample-time profile w.r.t. focal points (FP) along a scanline (SL) for a channel into a piece-wise linear form. The maximum error between the approximated and accurate sample times of ADC is eight times the sample time resolution (Ts) that is 1/32 of the ultrasound signal period in this work. The non-uniform sampling reduces the FIFO size required for digital beamforming by around 20 times. By applying a 9-dot image from Field-II program and 2-D ultrasound phantom images to the fabricated RX beamformer chip, the original images were successfully reconstructed from the measured output. The chip in a 0.13-um CMOS occupies 30.25 [Formula: see text] and consumes 605 mW.

A single-chip 32-channel analog beamformer with 4-ns delay resolution and 768-ns maximum delay range for ultrasound medical imaging with a linear array transducer.

A single-chip 32-channel analog beamformer is proposed. It achieves a delay resolution of 4 ns and a maximum delay range of 768 ns. It has a focal-point based architecture, which consists of 7 sub-analog beamformers (sub-ABF). Each sub-ABF performs a RX focusing operation for a single focal point. Seven sub-ABFs perform a time-interleaving operation to achieve the maximum delay range of 768 ns. Phase interpolators are used in sub-ABFs to generate sampling clocks with the delay resolution of 4 ns from a low frequency system clock of 5 MHz. Each sub-ABF samples 32 echo signals at different times into sampling capacitors, which work as analog memory cells. The sampled 32 echo signals of each sub-ABF are originated from one target focal point at one instance. They are summed at one instance in a sub-ABF to perform the RX focusing for the target focal point. The proposed ABF chip has been fabricated in a 0.13- µ m CMOS process with an active area of 16 mm (2). The total power consumption is 287 mW. In measurement, the digital echo signals from a commercial ultrasound medical imaging machine were applied to the fabricated chip through commercial DAC chips. Due to the speed limitation of the DAC chips, the delay resolution was relaxed to 10 ns for the real-time measurement. A linear array transducer with no steering operation is used in this work.

An analog-digital hybrid RX beamformer chip with non-uniform sampling for ultrasound medical imaging with 2D CMUT array.

To reduce the memory area, a two-stage RX beamformer (BF) chip with 64 channels is proposed for the ultrasound medical imaging with a 2D CMUT array. The chip retrieved successfully two B-mode phantom images with a steering angle from -45 (°) to +45 (°), the maximum delay range of 8 µs, and the delay resolution of 6.25 ns. An analog-digital hybrid BF (HBF) is chosen for the proposed chip to utilize the easy beamforming operation in the digital domain and also to reduce chip area by minimizing the number of ADCs. The chip consists of eight analog beamformers (ABF) for the 1st-stage and a digital beamformer (DBF) for the 2nd-stage. The two-stage architecture reduces the memory area of both ABF and DBF by around four times. The DBF circuit is divided into three steps to further reduce the digital FIFO memory area by around twice. Coupled with the non-uniform sampling scheme, the proposed two-stage HBF chip reduces the total memory area by around 40 times compared to the uniform-sampling single-stage BF chip. The chip fabricated in a 0.13- µm CMOS process occupies the area of 19.4 mm(2), and dissipates 1.14 W with the analog supply of 3.3 V and the digital supply of 1.2 V.

Biological activities of fusarochromanone: a potent anti-cancer agent.

BACKGROUND: Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity. RESULTS: Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 µM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells. CONCLUSIONS: Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101's molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.

High throughput screening assay of alpha(1G) T-type Ca2+ channels and comparison with patch-clamp studies.

Whole-cell patch-clamp-based electrophysiological techniques are powerful tools for examining the biophysical and pharmacological properties of ion channels. However, the recent validation of ion channels as novel drug targets necessitates the development of a faster screening method for ion channels. Therefore, we have developed a rapid, reliable, and sensitive cell-based high throughput screening (HTS) assay for T-type Ca2+ channels. We had previously constructed HEK293/alpha(1G)/Kir2.1 cell lines that stably expressed alpha(1G) and Kir2.1 subunits [1] and found that alpha(1G) T-type channel-sensitive Ca2+ signals were detected by the application of high concentrations of KCl under fura-2-based single cell measurements of intracellular Ca2+ concentration ([Ca2+](i)). In the present study, we applied HEK293/alpha (1G)/Kir2.1 cells to the FDSS6000 (Functional Drug Screening System) to develop a fast and reliable cell-based HTS method for alpha(1G) T-type Ca2+ channels. After detecting 70 mM KCl-induced [Ca2+](i) increases using the FDSS6000 system, we verified this new alpha(1G) channel HTS system by examining two T-type Ca2+ channel blockers, Ni2+ and mibefradil, and measuring the Z'-factor (Z' factor = 0.66) in 96-well plates. Furthermore, we assayed selected 3,4-dihydroquinazolin derivatives using this FDSS6000-based alpha(1G) channel HTS system at the level of IC(50) values and compared the results with those obtained from whole-cell patch-clamp recordings. Taken together, our results suggest that the FDSS6000-based alpha(1G) channel HTS system is a fast and feasible assay for alpha(1G) T-type Ca2+ channels. This assay can be utilized as a primary screening method for T-type Ca2+ channel-targeted chemicals and for the development of HTS systems for other types of ion channels.

Discovery of potent T-type calcium channel blocker.

The intensive SAR study of 3,4-dihydroquinazoline series led to the most potent compound 10 (KYS05090: IC(50)=41+/-1 nM) against T-type calcium channel and its potency is nearly comparable to that of Kurtoxin. As a small organic molecule, this compound showed the highest blocking activity reported to date.

Lead discovery and optimization of T-type calcium channel blockers.

A series of compounds were designed as T-type calcium channel blocker containing 6 or 5 pharmacophore features from structure-based virtual screening. To optimize the suggested structure, over 130 derivatives were synthesized and their inhibitory activities on T-type calcium channel were assayed using in vitro screening system with alpha1(G) and alpha1(H) clones. For the compounds with higher activities in FDSS assay system, the efficacy was measured by patch-clamp method. Among the library with 5 features, alkaneamide derivatives (7b, 9j, 11b, 11g, 11h) with 4-arylsubstituted piperazine showed better IC(50) values than Mibefradil.

Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers.

A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 microM, respectively.

Synthesis and SAR studies of a novel series of T-type calcium channel blockers.

For the novel, potent, and selective T-type Ca2+ channel blockers, a series of sulfonamido-containing 3,4-dihydroquinazoline derivatives were prepared and evaluated for their blocking actions on T- and N-type Ca2+ channels. Among them, 9c (KYS05064, IC50 = 0.96 +/- 0.22 microM) was found to be as potent as Mibefradil and also showed the highest selectivity for T-type Ca2+ channel with no effect on N-type Ca2+ channel.