Facilitation of I Kr current by some hERG channel blockers suppresses early afterdepolarizations.

Drug-induced block of the cardiac rapid delayed rectifying potassium current (I Kr), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Here we propose a mechanism that could explain why certain clinically used hERG blockers are less proarrhythmic than others. We demonstrate that several drugs that block hERG channels, but have favorable cardiac safety profiles, also evoke another effect; they facilitate the hERG current amplitude in response to low-voltage depolarization. To investigate how hERG facilitation impacts cardiac safety, we develop computational models of I Kr block with and without this facilitation. We constrain the models using data from voltage clamp recordings of hERG block and facilitation by nifekalant, a safe class III antiarrhythmic agent. Human ventricular action potential simulations demonstrate the ability of nifekalant to suppress ectopic excitations, with or without facilitation. Without facilitation, excessive I Kr block evokes early afterdepolarizations, which cause lethal arrhythmias. When facilitation is introduced, early afterdepolarizations are prevented at the same degree of block. Facilitation appears to prevent early afterdepolarizations by increasing I Kr during the repolarization phase of action potentials. We empirically test this prediction in isolated rabbit ventricular myocytes and find that action potential prolongation with nifekalant is less likely to induce early afterdepolarization than action potential prolongation with dofetilide, a hERG channel blocker that does not induce facilitation. Our data suggest that hERG channel blockers that induce facilitation increase the repolarization reserve of cardiac myocytes, rendering them less likely to trigger lethal ventricular arrhythmias

High sensitivity and multifunctional micro-Hall sensors fabricated using InAlSb/InAsSb/InAlSb heterostructures

Further diversification of Hall sensor technology requires development of materials with high electron mobility and an ultrathin conducting layer very close to the material's surface. Here, we describe the magnetoresistive properties of micro-Hall devices fabricated using InAlSb/InAsSb/InAlSb heterostructures where electrical conduction was confined to a 30 nm-InAsSb two-dimensional electron gas layer. The 300 K electron mobility and sheet carrier concentration were 36 500 cm(2) V-1 s(-1) and 2.5 x 10(11) cm(-2), respectively. The maximum current-related sensitivity was 2 750 V A(-1) T-1, which was about an order of magnitude greater than AlGaAs/InGaAs pseudomorphic heterostructures devices. Photolithography was used to fabricate 1 mu m x 1 mu m Hall probes, which were installed into a scanning Hall probe microscope and used to image the surface of a hard disk

Pengaruh Proses Produksi dan Pengendalian Kualitas terhadap Kualitas Produk Baby Blanket Saku Print di PT. Dialogue Garmindo Utama

Tujuan dari penelitian ini yaitu untuk mengetahui seberapa besar pengaruh yang ditimbulkan oleh proses produksi dan pengendalian kualitas terhadap kualitas produk yang dihasilkan baik secara parsial maupun simultan. Kualitas produk adalah kemampuan suatu produk untuk melaksanakan fungsinya, meliputi daya tahan, keandalan, ketepatan, kemudahan operasi dan perbaikan, serta atribut bernilai lainnya. Dengan kata lain produksi dikatakan berhasil apabila dapat menghasilkan produk yang berkualitas sesuai dengan yang diharapkan. Objek penelitian ini adalah Perusahaan yang melakukan proses produksi dalam skala menengah keatas dan hasil produksinya sudah beredar di pasar luas. Teknik yang digunakan dalam penelitian ini adalah path analysis dengan menggunakan SPSS 21. Kesimpulannya proses produksi dan pengendalian kualitas secara bersama-sama berpengaruh terhadap kualitas produk yang dihasilkan dengan nilai koefisisen determinasi 82,9%

KARAKTERISTIK FISIKOKIMIA EKSTRAK MADU DAN PROPOLIS TRIGONA SP. ASAL LOMBOK UTARA

Cultivation of honey and propolis Trigona sp. in the area of North Lombok Regency is growing, but has not equipped with scientific data regarding its physicochemical characteristics. This research aims to determine the physicochemical characteristics of honey and propolis extract of Trigona sp. from North Lombok. Physical parameters measured of the ethanol extract of honey and propolis Trigona sp. includes moisture content and ash content using gravimetric methods; Meanwhile, chemical parameters are identification of compounds using phytochemical screening methods and GC-MS (Gas Chromatography-Mass Spectrometry) instruments. Ethanol extract of honey Trigona sp. has moisture and ash content values of 9.38 ± 0.28% and 1.23 ± 0.02%, respectively; while the extract of propolis Trigona sp. containing water content and ash content of 11.64 ± 0.15% and 1.85 ± 0.02%. Ethanol extract of honey Trigona sp. identified positively containing flavonoid and alkaloid compounds, as well as 16 other compounds identified using GC-MS. Trigona sp. propolis extract contains flavonoids, alkaloids, tannins, saponins, and 10 compounds identified using GC-MS

Radio and gamma-ray constraints on dark matter annihilation in the Galactic center

We determine upper limits on the dark matter (DM) self-annihilation cross section for scenarios in which annihilation leads to the production of electron--positron pairs. In the Galactic centre (GC), relativistic electrons and positrons produce a radio flux via synchroton emission, and a gamma ray flux via bremsstrahlung and inverse Compton scattering. On the basis of archival, interferometric and single-dish radio data, we have determined the radio spectrum of an elliptical region around the Galactic centre of extent 3 degrees semi-major axis (along the Galactic plane) and 1 degree semi-minor axis and a second, rectangular region, also centered on the GC, of extent 1.6 degrees x 0.6 degrees. The radio spectra of both regions are non-thermal over the range of frequencies for which we have data: 74 MHz -- 10 GHz. We also consider gamma-ray data covering the same region from the EGRET instrument (about GeV) and from HESS (around TeV). We show how the combination of these data can be used to place robust constraints on DM annihilation scenarios, in a way which is relatively insensitive to assumptions about the magnetic field amplitude in this region. Our results are approximately an order of magnitude more constraining than existing Galactic centre radio and gamma ray limits. For a DM mass of m_\chi =10 GeV, and an NFW profile, we find that the velocity-averaged cross-section must be less than a few times 10^-25 cm^3 s^-1.Comment: 14 pages, 9 figures. Version accepted for publication in PRD. Reference section updated/extended

Reserve Accumulation Is Prioritized Over Growth Following Single or Combined Injuries in Three Common North American Urban Tree Species

Trees that grow in urban areas are confronted with a wide variety of stresses that undermine their long-term survival. These include mechanical damage to the crown, root reduction and stem injury, all of which remove significant parts of plant tissues. The single or combined effects of these stresses generate a complex array of growth and ecophysiological responses that are hard to predict. Here we evaluated the effects of different individual and combined damage on the dynamics of non-structural carbohydrates (NSC, low weight sugars plus starch) concentration and new tissue growth (diameter increment) in young trees. We hypothesized that (i) tissue damage will induce larger reductions in diameter growth than in NSC concentrations and (ii) combinations of stress treatments that minimally alter the "functional equilibrium" (e.g., similar reductions of leaf and root area) would have the least impact on NSC concentrations (although not on growth) helping to maintain tree health and integrity. To test these hypotheses, we set up a manipulative field experiment with 10-year-old trees of common urban species (Celtis occidentalis, Fraxinus pennsylvanica, and Tilia cordata). These trees were treated with a complete array of mechanical damage combinations at different levels of intensity (i.e., three levels of defoliation and root reduction, and two levels of stem damage). We found that tree growth declined in relation to the total amount of stress inflicted on the trees, i.e., when the combined highest level of stress was applied, but NSC concentrations were either not affected or, in some cases, increased with an increasing level of stress. We did not find a consistent response in concentration of reserves in relation to the combined stress treatments. Therefore, trees appear to reach a new "functional equilibrium" that allows them to adjust their levels of carbohydrate reserves, especially in stems and roots, to meet their metabolic demand under stressful situations. Our results provide a unique insight into the carbon economy of trees facing multiple urban stress conditions in order to better predict long-term tree performance and vitality

A Comparative Study of the Parker Instability under Three Models of the Galactic Gravity

To examine how non-uniform nature of the Galactic gravity might affect length and time scales of the Parker instability, we took three models of gravity, uniform, linear and realistic ones. To make comparisons of the three gravity models on a common basis, we first fixed the ratio of magnetic pressure to gas pressure at $\alpha$ = 0.25, that of cosmic-ray pressure at $\beta$ = 0.4, and the rms velocity of interstellar clouds at $a_s$ = 6.4 km s$^{-1}$, and then adjusted parameters of the gravity models in such a way that the resulting density scale heights for the three models may all have the same value of 160 pc. Performing linear stability analyses onto equilibrium states under the three models with the typical ISM conditions, we calculate the maximum growth rate and corresponding length scale for each of the gravity models. Under the uniform gravity the Parker instability has the growth time of 1.2$\times10^{8}$ years and the length scale of 1.6 kpc for symmetric mode. Under the realistic gravity it grows in 1.8$\times10^{7}$ years for both symmetric and antisymmetric modes, and develops density condensations at intervals of 400 pc for the symmetric mode and 200 pc for the antisymmetric one. A simple change of the gravity model has thus reduced the growth time by almost an order of magnitude and its length scale by factors of four to eight. These results suggest that an onset of the Parker instability in the ISM may not necessarily be confined to the regions of high $\alpha$ and $\beta$.Comment: Accepted for publication in ApJ, using aaspp4.sty, 18 text pages with 9 figure

Low density molecular gas in the galaxy

The distributions and physical conditions in molecular gas in the interstellar medium have been investigated in both the Galaxy and towards external galaxies. For example, Galactic plane surveys in the CO J =1-0 line with the Columbia 1.2-m telescope and with the Five College Radio Astronomy Observatory (FCRAO) 14-m telescopes have been able to trace spiral arms more clearly than HI surveys have been able to reveal, and indicate that most of molecular mass is contained in Giant Molecular Clouds (GMCs). Extensive maps of the whole Milky Way showed two prominent features, the 4-kpc molecular ring and the Galactic center. The physical conditions in the Galaxy have been studied by comparing the intensity of CO J =1-0 line with those of other lines, e.g., 13CO J =1-0, higher J transitions of CO, and dense gas tracers such as HCO+, CS, and HCN. Previous studies were however strongly biased towards regions where CO emission was known to be intense. The radial distribution of molecular hydrogen shows that most of the H2 gas which is indirectly traced by observations of its associated CO emission, originates from the inner Galaxy (Dame 1993). Extending outwards from a galacto-centric distance of ~7 kpc, the H2 mass surface density decreases dramatically, and HI dominates over H2 in the outer Galaxy. What are physical conditions of molecular gas where the CO emission is relatively weak, and can we really trace all of the molecular gas through obervations of CO? These kinds of problems have not been solved yet, but are addressed in our study