632 research outputs found

    1-a-Phellandrene and its monohydrochloride. Part 1

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    Utilising solution processed zirconium acetylacetonate as an electron extracting layer in both regular and inverted small molecule organic photovoltaic cells

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    Interfacial layers are commonly employed in organic photovoltaic (OPV) cells in order to improve device performance. These layers must be transparent, stable, be compatible with the photo-active materials and provide efficient charge extraction with a good energetic match to the relevant organic material. In this report we demonstrate the compatibility of zirconium acetylacetonate (ZrAcac) electron extracting layers in both regular and inverted small molecule OPV cells. When the ZrAcac was processed in both air and under N2, low work function (3.9 and 3.7 eV respectively), highly transparent layers were formed, with good energetic alignment to both C60 and hexachlorinated boron subphthalocyanine chloride (Cl6-SubPc) acceptors. Initial measurements indicate similar stabilities when using the ZrAcac in either device architecture. These results indicate that the ZrAcac layer can be used as a direct replacement for the commonly used bathocuproine (BCP) in small molecule OPV cells

    An Acheulean handaxe from Gladysvale Cave site, Gauteng, South Africa.

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    WE DESCRIBE A SINGLE HANDAXE FROM fossiliferous breccias at Gladysvale Cave, South Africa. The artefact is the only known tool so far discovered during the controlled excavations conducted at this site over the last decade, and was recovered from decalcified sediments near the stratigraphic interface of two breccia units, making it difficult to assign it with confidence to either. The morphology of the handaxe indicates a middle-late Acheulean industry, and preliminary electron spin resonance and palaeomagnetic dating suggest an age of greater than 780 000 years.NCS2016http://hdl.handle.net/10520/EJC9652

    Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome:Insights from virtual human atria

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    Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF

    Buffer gas cooling and trapping of atoms with small magnetic moments

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    Buffer gas cooling was extended to trap atoms with small magnetic moment (mu). For mu greater than or equal to 3mu_B, 1e12 atoms were buffer gas cooled, trapped, and thermally isolated in ultra high vacuum with roughly unit efficiency. For mu < 3mu_B, the fraction of atoms remaining after full thermal isolation was limited by two processes: wind from the rapid removal of the buffer gas and desorbing helium films. In our current apparatus we trap atoms with mu greater than or equal to 1.1mu_B, and thermally isolate atoms with mu greater than or equal to 2mu_B. Extrapolation of our results combined with simulations of the loss processes indicate that it is possible to trap and evaporatively cool mu = 1mu_B atoms using buffer gas cooling.Comment: 17 pages, 4 figure

    In silico Assessment of Pharmacotherapy for Human Atrial Patho-Electrophysiology Associated With hERG-Linked Short QT Syndrome

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    Short QT syndrome variant 1 (SQT1) arises due to gain-of-function mutations to the human Ether-Ă -go-go-Related Gene (hERG), which encodes the α subunit of channels carrying rapid delayed rectifier potassium current, IKr. In addition to QT interval shortening and ventricular arrhythmias, SQT1 is associated with increased risk of atrial fibrillation (AF), which is often the only clinical presentation. However, the underlying basis of AF and its pharmacological treatment remain incompletely understood in the context of SQT1. In this study, computational modeling was used to investigate mechanisms of human atrial arrhythmogenesis consequent to a SQT1 mutation, as well as pharmacotherapeutic effects of selected class I drugs–disopyramide, quinidine, and propafenone. A Markov chain formulation describing wild type (WT) and N588K-hERG mutant IKr was incorporated into a contemporary human atrial action potential (AP) model, which was integrated into one-dimensional (1D) tissue strands, idealized 2D sheets, and a 3D heterogeneous, anatomical human atria model. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone, including binding kinetics for IKr/hERG and sodium current, INa, were considered. Heterozygous and homozygous formulations of the N588K-hERG mutation shortened the AP duration (APD) by 53 and 86 ms, respectively, which abbreviated the effective refractory period (ERP) and excitation wavelength in tissue, increasing the lifespan and dominant frequency (DF) of scroll waves in the 3D anatomical human atria. At the concentrations tested in this study, quinidine most effectively prolonged the APD and ERP in the setting of SQT1, followed by disopyramide and propafenone. In 2D simulations, disopyramide and quinidine promoted re-entry termination by increasing the re-entry wavelength, whereas propafenone induced secondary waves which destabilized the re-entrant circuit. In 3D simulations, the DF of re-entry was reduced in a dose-dependent manner for disopyramide and quinidine, and propafenone to a lesser extent. All of the anti-arrhythmic agents promoted pharmacological conversion, most frequently terminating re-entry in the order quinidine &gt; propafenone = disopyramide. Our findings provide further insight into mechanisms of SQT1-related AF and a rational basis for the pursuit of combined IKr and INa block based pharmacological strategies in the treatment of SQT1-linked AF

    In silico Assessment of Pharmacotherapy for Human Atrial Patho-Electrophysiology Associated With hERG-Linked Short QT Syndrome

    Get PDF
    Short QT syndrome variant 1 (SQT1) arises due to gain-of-function mutations to the human Ether-Ă -go-go-Related Gene (hERG), which encodes the α subunit of channels carrying rapid delayed rectifier potassium current, IKr. In addition to QT interval shortening and ventricular arrhythmias, SQT1 is associated with increased risk of atrial fibrillation (AF), which is often the only clinical presentation. However, the underlying basis of AF and its pharmacological treatment remain incompletely understood in the context of SQT1. In this study, computational modeling was used to investigate mechanisms of human atrial arrhythmogenesis consequent to a SQT1 mutation, as well as pharmacotherapeutic effects of selected class I drugs–disopyramide, quinidine, and propafenone. A Markov chain formulation describing wild type (WT) and N588K-hERG mutant IKr was incorporated into a contemporary human atrial action potential (AP) model, which was integrated into one-dimensional (1D) tissue strands, idealized 2D sheets, and a 3D heterogeneous, anatomical human atria model. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone, including binding kinetics for IKr/hERG and sodium current, INa, were considered. Heterozygous and homozygous formulations of the N588K-hERG mutation shortened the AP duration (APD) by 53 and 86 ms, respectively, which abbreviated the effective refractory period (ERP) and excitation wavelength in tissue, increasing the lifespan and dominant frequency (DF) of scroll waves in the 3D anatomical human atria. At the concentrations tested in this study, quinidine most effectively prolonged the APD and ERP in the setting of SQT1, followed by disopyramide and propafenone. In 2D simulations, disopyramide and quinidine promoted re-entry termination by increasing the re-entry wavelength, whereas propafenone induced secondary waves which destabilized the re-entrant circuit. In 3D simulations, the DF of re-entry was reduced in a dose-dependent manner for disopyramide and quinidine, and propafenone to a lesser extent. All of the anti-arrhythmic agents promoted pharmacological conversion, most frequently terminating re-entry in the order quinidine > propafenone = disopyramide. Our findings provide further insight into mechanisms of SQT1-related AF and a rational basis for the pursuit of combined IKr and INa block based pharmacological strategies in the treatment of SQT1-linked AF.</p

    Optimization of a high work function solution processed vanadium oxide hole-extracting layer for small molecule and polymer organic photovoltaic cells

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    We report a method of fabricating a high work function, solution processable vanadium oxide (V2Ox(sol)) hole-extracting layer. The atmospheric processing conditions of film preparation have a critical influence on the electronic structure and stoichiometry of the V2Ox(sol), with a direct impact on organic photovoltaic (OPV) cell performance. Combined Kelvin probe (KP) and ultraviolet photoemission spectroscopy (UPS) measurements reveal a high work function, n-type character for the thin films, analogous to previously reported thermally evaporated transition metal oxides. Additional states within the band gap of V2Ox(sol) are observed in the UPS spectra and are demonstrated using X-ray photoelectron spectroscopy (XPS) to be due to the substoichiometric nature of V2Ox(sol). The optimized V2Ox(sol) layer performance is compared directly to bare indium–tin oxide (ITO), poly(ethyleneoxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and thermally evaporated molybdenum oxide (MoOx) interfaces in both small molecule/fullerene and polymer/fullerene structures. OPV cells incorporating V2Ox(sol) are reported to achieve favorable initial cell performance and cell stability attributes
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