338 research outputs found

    Quantum Rod Emission Coupled to Plasmonic Lattice Resonances: A Collective Directional Source of Polarized Light

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    We demonstrate that an array of optical antennas may render a thin layer of randomly oriented semiconductor nanocrystals into an enhanced and highly directional source of polarized light. The array sustains collective plasmonic lattice resonances which are in spectral overlap with the emission of the nanocrystals over narrow angular regions. Consequently, different photon energies of visible light are enhanced and beamed into definite directions.Comment: 4 pages, 3 figure

    Metallothioneins 2 and 3 contribute to the metal-adapted phenotype but are not directly linked to Zn accumulation in the metal hyperaccumulator, Thlaspi caerulescens

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    To study the role of metallothioneins (MTs) in Zn accumulation, the expression of TcMT2a, TcMT2b, and TcMT3 was analysed in three accessions and 15 F3 families of two inter-accession crosses of the Cd/Zn hyperaccumulator Thlaspi caerulescens, with different degrees of Zn accumulation. The highest expression levels were found in the shoots of a superior metal-accumulating calamine accession from St Laurent le Minier, with >10-fold TcMT3 expression compared with another calamine accession and a non-metallicolous accession. Moreover, F3 sibling lines from the inter-accession crosses that harboured the MT2a or MT3 allele from St Laurent le Minier had higher expression levels. However, there was no co-segregation of TcMT2a or TcMT3 expression and Zn accumulation. To examine the functions of TcMTs in plants, TcMT2a and TcMT3 were ectopically expressed in Arabidopsis. The transformant lines had reduced root length in control medium but not at high metal concentrations, suggesting that the ectopically expressed proteins interfered with the physiological availability of essential metals under limited supply. The Arabidopsis transformant lines did not show increased tolerance to Cd, Cu, or Zn, nor increased Cd or Zn accumulation. Immunohistochemical analysis indicated that in roots, MT2 protein is localized in the epidermis and root hairs of both T. caerulescens and Arabidopsis thaliana. The results suggest that TcMT2a, TcMT2b, and TcMT3 are not primarily involved in Zn accumulation as such. However, the elevated expression levels in the metallicolous accessions suggests that they do contribute to the metal-adapted phenotype, possibly through improving Cu homeostasis at high Zn and Cd body burdens. Alternatively, they might function as hypostatic enhancers of Zn or Cd tolerance

    Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

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    Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend <sup>®</sup> excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies

    Validation of the TROPOspheric Monitoring Instrument (TROPOMI) surface UV radiation product

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    The TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor (S5P) satellite was launched on 13 October 2017 to provide the atmospheric composition for atmosphere and climate research. The S5P is a Sun-synchronous polar-orbiting satellite providing global daily coverage. The TROPOMI swath is 2600 km wide, and the ground resolution for most data products is 7:23:5 km2 (5:63:5 km2 since 6 August 2019) at nadir. The Finnish Meteorological Institute (FMI) is responsible for the development of the TROPOMI UV algorithm and the processing of the TROPOMI surface ultraviolet (UV) radiation product which includes 36 UV parameters in total. Ground-based data from 25 sites located in arctic, subarctic, temperate, equatorial and Antarctic areas were used for validation of the TROPOMI overpass irradiance at 305, 310, 324 and 380 nm, overpass erythemally weighted dose rate/UV index, and erythemally weighted daily dose for the period from 1 January 2018 to 31 August 2019. The validation results showed that for most sites 60 % 80% of TROPOMI data was within 20% of ground-based data for snow-free surface conditions. The median relative differences to ground-based measurements of TROPOMI snow-free surface daily doses were within 10% and 5% at two-Thirds and at half of the sites, respectively. At several sites more than 90% of cloud-free TROPOMI data was within 20% of groundbased measurements. Generally median relative differences between TROPOMI data and ground-based measurements were a little biased towards negative values (i.e. satellite data ground-based measurement), but at high latitudes where non-homogeneous topography and albedo or snow conditions occurred, the negative bias was exceptionally high: from 30% to 65 %. Positive biases of 10 % 15% were also found for mountainous sites due to challenging topography. The TROPOMI surface UV radiation product includes quality flags to detect increased uncertainties in the data due to heterogeneous surface albedo and rough terrain, which can be used to filter the data retrieved under challenging conditions

    The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

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    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases

    POLG1 p.R722H mutation associated with multiple mtDNA deletions and a neurological phenotype

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    <p>Abstract</p> <p>Background</p> <p>The c.2447G>A (p.R722H) mutation in the gene <it>POLG1 </it>of the catalytic subunit of human mitochondrial polymerase gamma has been previously found in a few occasions but its pathogenicity has remained uncertain. We set out to ascertain its contribution to neuromuscular disease.</p> <p>Methods</p> <p>Probands from two families with probable mitochondrial disease were examined clinically, muscle and buccal epithelial DNA were analyzed for mtDNA deletions, and the <it>POLG1, POLG2, ANT1 </it>and <it>Twinkle </it>genes were sequenced.</p> <p>Results</p> <p>An adult proband presented with progressive external ophthalmoplegia, sensorineural hearing impairment, diabetes mellitus, dysphagia, a limb myopathy and dementia. Brain MRI showed central and cortical atrophy, and <sup>18</sup>F-deoxyglucose PET revealed reduced glucose uptake. Histochemical analysis of muscle disclosed ragged red fibers and cytochrome c oxidase-negative fibers. Electron microscopy showed subsarcolemmal aggregates of morphologically normal mitochondria. Multiple mtDNA deletions were found in the muscle, and sequencing of the <it>POLG1 </it>gene revealed a homozygous c.2447G>A (p.R722H) mutation. His two siblings were also homozygous with respect to the p.R722H mutation and presented with dementia and sensorineural hearing impairment. In another family the p.R722H mutation was found as compound heterozygosity with the common p.W748S mutation in two siblings with mental retardation, ptosis, epilepsy and psychiatric symptoms. The estimated carrier frequency of the p.R722H mutation was 1:135 in the Finnish population. No mutations in <it>POLG2</it>, <it>ANT1 </it>and <it>Twinkle </it>genes were found. Analysis of the POLG1 sequence by homology modeling supported the notion that the p.R722H mutation is pathogenic.</p> <p>Conclusions</p> <p>The recessive c.2447G>A (p.R722H) mutation in the linker region of the <it>POLG1 </it>gene is pathogenic for multiple mtDNA deletions in muscle and is associated with a late-onset neurological phenotype as a homozygous state. The onset of the disease can be earlier in compound heterozygotes.</p

    Surface Doping Quantum Dots with Chemically Active Native Ligands: Controlling Valence without Ligand Exchange

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    One remaining challenge in the field of colloidal semiconductor nanocrystal quantum dots is learning to control the degree of functionalization or valence per nanocrystal. Current quantum dot surface modification strategies rely heavily on ligand exchange, which consists of replacing the nanocrystal\u27s native ligands with carboxylate- or amine-terminated thiols, usually added in excess. Removing the nanocrystal\u27s native ligands can cause etching and introduce surface defects, thus affecting the nanocrystal\u27s optical properties. More importantly, ligand exchange methods fail to control the extent of surface modification or number of functional groups introduced per nanocrystal. Here, we report a fundamentally new surface ligand modification or doping approach aimed at controlling the degree of functionalization or valence per nanocrystal while retaining the nanocrystal\u27s original colloidal and photostability. We show that surface-doped quantum dots capped with chemically active native ligands can be prepared directly from a mixture of ligands with similar chain lengths. Specifically, vinyl and azide-terminated carboxylic acid ligands survive the high temperatures needed for nanocrystal synthesis. The ratio between chemically active and inactive-terminated ligands is maintained on the nanocrystal surface, allowing to control the extent of surface modification by straightforward organic reactions. Using a combination of optical and structural characterization tools, including IR and 2D NMR, we show that carboxylates bind in a bidentate chelate fashion, forming a single monolayer of ligands that are perpendicular to the nanocrystal surface. Moreover, we show that mixtures of ligands with similar chain lengths homogeneously distribute themselves on the nanocrystal surface. We expect this new surface doping approach will be widely applicable to other nanocrystal compositions and morphologies, as well as to many specific applications in biology and materials science
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