Organic-inorganic hybrid perovskites are emerging low-cost emitters with very high color purity, but their low luminescent efficiency is a critical drawback. We boosted the current efficiency (CE) of ...perovskite light-emitting diodes with a simple bilayer structure to 42.9 candela per ampere, similar to the CE of phosphorescent organic light-emitting diodes, with two modifications: We prevented the formation of metallic lead (Pb) atoms that cause strong exciton quenching through a small increase in methylammonium bromide (MABr) molar proportion, and we spatially confined the exciton in uniform MAPbBr₃ nanograins (average diameter = 99.7 nanometers) formed by a nanocrystal pinning process and concomitant reduction of exciton diffusion length to 67 nanometers. These changes caused substantial increases in steady-state photoluminescence intensity and efficiency of MAPbBr₃ nanograin layers.
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OATP1B1 (SLCO1B1) is predominantly expressed at the basolateral membrane of hepatocytes and is critically important for the hepatic uptake and clearance of numerous drug substrates and endogenous ...compounds. In general, the organic anion transporting polypeptides (OATP; SLCO) represent a superfamily of uptake transporters that mediate the sodium‐independent transport of a diverse range of amphipathic organic compounds including bile salts, steroid conjugates, thyroid hormones, anionic peptides, numerous drugs and other xenobiotic substances. OATP1B1 is highly polymorphic and a number of relevant and ethnically dependent polymorphisms have been identified and functionally characterized. In particular, the SLCO1B1 521T>C and 388A>G polymorphisms are commonly occurring variants in ethnically diverse populations and numerous in vitro and clinical studies have evaluated the consequences of these variants to interindividual differences in drug disposition and response. OATP1B1 is particularly important for the disposition of HMG‐CoA reductase inhibitors, or statins, as it is known to efficiently transport most statins to their site of action within hepatocytes. Many studies have focused on the consequences of OATP1B1 variants to statin disposition in vitro and in vivo and would suggest that genetic variability in SLCO1B1 has important implications for statin pharmacokinetics, risk for statin‐induced myopathy, and modulation of statin treatment response. This review describes what is currently known regarding SLCO1B1 genotype, OATP1B1 protein expression and interindividual and interethnic consequences to drug disposition, with particular focus on statin pharmacokinetics and implications for drug response and toxicity.
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The organic anion transporting polypeptides (OATPs) are a superfamily of drug transporters involved in the uptake and disposition of a wide array of structurally divergent endogenous and exogenous ...substrates, including steroid hormones, bile acids, and commonly used drugs, such as anti-infectives, antihypertensives, and cholesterol lowering agents. In the past decade, OATPs, primarily OATP1A2, OATP1B1, and OATP1B3, have emerged as potential mediators of chemotherapy disposition, including drugs such as methotrexate, doxorubicin, paclitaxel, docetaxel, irinotecan and its important metabolite 7-ethyl-10-hydroxycamptothecin, and certain tyrosine kinase inhibitors. Furthermore, OATP family members are polymorphic and numerous studies have shown OATP variants to have differential uptake, disposition, and/or pharmacokinetics of numerous drug substrates with important implications for interindividual differences in efficacy and toxicity. Additionally, certain OATPs have been found to be overexpressed in a variety of human solid tumors, including breast, liver, colon, pancreatic, and ovarian cancers, suggesting potential roles for OATPs in tumor development and progression and as novel targets for cancer therapy. This review focuses on the emerging roles for selected OATPs in cancer pharmacology, including preclinical and clinical studies suggesting roles in chemotherapy disposition, the pharmacogenetics of OATPs in cancer therapy, and OATP overexpression in various tumor tissues with implications for OATPs as therapeutic targets.
Under intense laser excitation, thin films and suspensions of graphite and its nanostructure, including carbon black, nanotubes, few-layer graphenes and graphene oxides, exhibit induced transparency ...due to saturable absorption. This switches to optical limiting only at very high fluences when induced breakdown gives rise to microbubbles and microplasmas that causes nonlinear scattering. Here, we show that dispersed graphenes, in contrast, can exhibit broadband nonlinear optical absorption at fluences well below this damage threshold with a strong matrix effect. We obtained, for nanosecond visible and near-infrared pulses, a new benchmark for optical energy-limiting onset of 10 mJ cm-2 for a linear transmittance of 70%, with excellent output clamping in both heavy-atom solvents and polymer film matrices. Nanosecond pump-probe spectroscopy in chlorobenzene reveals that the nanographene domains switch from the usual broadband photo-induced bleaching to a novel reverse saturable absorption mechanism with increasing excitation densities across this threshold.
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Dissipationless currents from topologically protected states are promising for disorder-tolerant electronics and quantum computation. Here, we photogenerate giant anisotropic terahertz nonlinear ...currents with vanishing scattering, driven by laser-induced coherent phonons of broken inversion symmetry in a centrosymmetric Dirac material ZrTe5. Our work suggests that this phononic terahertz symmetry switching leads to formation of Weyl points, whose chirality manifests in a transverse, helicity-dependent current, orthogonal to the dynamical inversion symmetry breaking axis, via circular photogalvanic effect. The temperature-dependent topological photocurrent exhibits several distinct features: Berry curvature dominance, particle–hole reversal near conical points and chirality protection that is responsible for an exceptional ballistic transport length of ~10 μm. These results, together with first-principles modelling, indicate two pairs of Weyl points dynamically created by B1u phonons of broken inversion symmetry. Such phononic terahertz control breaks ground for coherent manipulation of Weyl nodes and robust quantum transport without application of static electric or magnetic fields.Femtosecond optical pulses are used to generate coherent phonons that break inversion symmetry and drive anisotropic terahertz photocurrents in the topological material ZrTe5.
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Structural Basis of Transcription Initiation Zhang, Yu; Feng, Yu; Chatterjee, Sujoy ...
Science (American Association for the Advancement of Science),
11/2012, Volume:
338, Issue:
6110
Journal Article
Peer reviewed
Open access
During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 Å resolution of ...functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, σ A , and a promoter DNA fragment corresponding to the transcription bubble and downstream double-stranded DNA of the RNAP-promoter open complex. The structures show that σ recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between σ and template-strand single-stranded DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP active center.
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Pulmonary dead space fraction (Vd/Vt) is an independent predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is seldom used in practice. The ventilatory ratio is a simple ...bedside index that can be calculated using routinely measured respiratory variables and is a measure of impaired ventilation. Ventilatory ratio is defined as minute ventilation (ml/min) × Pa
(mm Hg)/(predicted body weight × 100 × 37.5).
To determine the relation of ventilatory ratio with Vd/Vt in ARDS.
First, in a single-center, prospective observational study of ARDS, we tested the association of Vd/Vt with ventilatory ratio. With in-hospital mortality as the primary outcome and ventilator-free days as the secondary outcome, we tested the role of ventilatory ratio as an outcome predictor. The findings from this study were further verified in secondary analyses of two NHLBI ARDS Network randomized controlled trials.
Ventilatory ratio positively correlated with Vd/Vt. Ordinal groups of ventilatory ratio had significantly higher Vd/Vt. Ventilatory ratio was independently associated with increased risk of mortality after adjusting for Pa
/Fi
, and positive end-expiratory pressure (odds ratio, 1.51; P = 0.024) and after adjusting for Acute Physiologic Assessment and Chronic Health Evaluation II score (odds ratio, 1.59; P = 0.04). These findings were further replicated in secondary analyses of two separate NHLBI randomized controlled trials.
Ventilatory ratio correlates well with Vd/Vt in ARDS, and higher values at baseline are associated with increased risk of adverse outcomes. These results are promising for the use of ventilatory ratio as a simple bedside index of impaired ventilation in ARDS.
Abstract
Perovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during ...operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation.
Heterostructures are central to the efficient manipulation of charge carriers, excitons and photons for high-performance semiconductor devices. Although these can be formed by stepwise evaporation of ...molecular semiconductors, they are a considerable challenge for polymers owing to re-dissolution of the underlying layers. Here we demonstrate a simple and versatile photocrosslinking methodology based on sterically hindered bis(fluorophenyl azide)s. The photocrosslinking efficiency is high and dominated by alkyl side-chain insertion reactions, which do not degrade semiconductor properties. We demonstrate two new back-infiltrated and contiguous interpenetrating donor-acceptor heterostructures for photovoltaic applications that inherently overcome internal recombination losses by ensuring path continuity to give high carrier-collection efficiency. This provides the appropriate morphology for high-efficiency polymer-based photovoltaics. We also demonstrate photopatternable polymer-based field-effect transistors and light-emitting diodes, and highly efficient separate-confinement-heterostructure light-emitting diodes. These results open the way to the general development of high-performance polymer semiconductor heterostructures that have not previously been thought possible.
The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four ...Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.
Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete CR plus partial responses PR and stable disease SD) and overall survival (OS).
Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.
This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.
ClinicalTrials.gov NCT00712790.
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