The ability to silence the activity of genetically specified neurons in a temporally precise fashion would open up the ability to investigate the causal role of specific cell classes in neural computations, behaviors, and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate very powerful, safe, multiple-color silencing of neural activity. The gene archaerhodopsin-31 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. In addition, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally-relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins2,3 or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans4 (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue vs. red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of “optogenetic” voltage and ion modulator, which will broadly empower new neuroscientific, biological, neurological, and psychiatric investigations.
Organic-inorganic hybrid perovskites have cemented their position as an exceptional class of optoelectronic materials thanks to record photovoltaic efficiencies of 22.1%, as well as promising demonstrations of light-emitting diodes, lasers, and light-emitting transistors. Perovskite materials with photoluminescence quantum yields close to 100% and perovskite light-emitting diodes with external quantum efficiencies of 8% and current efficiencies of 43 cd A(-1) have been achieved. Although perovskite light-emitting devices are yet to become industrially relevant, in merely two years these devices have achieved the brightness and efficiencies that organic light-emitting diodes accomplished in two decades. Further advances will rely decisively on the multitude of compositional, structural variants that enable the formation of lower-dimensionality layered and three-dimensional perovskites, nanostructures, charge-transport materials, and device processing with architectural innovations. Here, the rapid advancements in perovskite light-emitting devices and lasers are reviewed. The key challenges in materials development, device fabrication, operational stability are addressed, and an outlook is presented that will address market viability of perovskite light-emitting devices.
Hot-carrier solar cells can overcome the Shockley-Queisser limit by harvesting excess energy from hot carriers. Inorganic semiconductor nanocrystals are considered prime candidates. However, hot-carrier harvesting is compromised by competitive relaxation pathways (for example, intraband Auger process and defects) that overwhelm their phonon bottlenecks. Here we show colloidal halide perovskite nanocrystals transcend these limitations and exhibit around two orders slower hot-carrier cooling times and around four times larger hot-carrier temperatures than their bulk-film counterparts. Under low pump excitation, hot-carrier cooling mediated by a phonon bottleneck is surprisingly slower in smaller nanocrystals (contrasting with conventional nanocrystals). At high pump fluence, Auger heating dominates hot-carrier cooling, which is slower in larger nanocrystals (hitherto unobserved in conventional nanocrystals). Importantly, we demonstrate efficient room temperature hot-electrons extraction (up to ∼83%) by an energy-selective electron acceptor layer within 1 ps from surface-treated perovskite NCs thin films. These insights enable fresh approaches for extremely thin absorber and concentrator-type hot-carrier solar cells.
AIDS patients undergoing autologous transplantation for lymphoma were treated with gene-modified peripheral blood derived (CD34+) hematopoietic progenitor cells (HPC) expressing 3 RNA-based anti-HIV moieties (Tat/Rev shRNA, TAR decoy and CCR5 ribozyme). In vitro analysis of gene-modified HPC showed no differences in the hematopoietic potential compared with non-transduced cells. In vitro estimates of gene marking were as high as 22% but declined to ~1% over 4 weeks of culture. Ethical study design required that patients were transplanted with both gene modified and unmanipulated hematopoietic progenitor cell apheresis products (HPC-A). All 4 infused patients engrafted (ANC>500) by day 11 post-infusion and showed no unexpected infusion related toxicities. Persistent vector marking in multiple cell lineages has been observed at low levels for up to 24 months as has expression of siRNA and ribozyme. This is the first demonstration of siRNA expression in human blood cells following transplantation of autologous gene-modified CD34+ HPC. These results support the development of an RNA-based cell therapy platform for HIV. Summary Stem cell gene therapy for HIV results in sustained RNA expression in the blood of patients for up to 2 years following transplant.
promise for low-cost solution processability. [1][2][3][4] Perovskite solar cells have experienced tremendous development in the past few years with power conversion efficiency (PCE) rapidly increased to over 20%. [5,6] Besides efficiency, another critical factor for practical application of perovskite solar cells is stability.Recently, Ruddlesden-Popper perovskites (RPPs) have been reported to have promising stability. [7][8][9] The RPPs can be structurally derived from their 3D counterparts with alternating organic ammonium layers and perovskite layers, giving the general formula of (RNH 3 ) 2 A n−1 M n X 3n+1 , where n represents the number of perovskite layers, RNH 3 is the organic spacer, and the A (small cation), M (divalent metal cation), and X (halide anion) form the perovskite framework. [10,11] The superior stability of RPPs can be attributed to the hydrophobic property of the organic spacer, which inhibits water molecules from penetrating and attacking the inorganic layers.Previous studies reported that RPPs exhibit enhanced stability but at the cost of reduced efficiency due to lower Recently, Ruddlesden-Popper perovskites (RPPs) have attracted increasing interests due to their promising stability. However, the efficiency of solar cells based on RPPs is much lower than that based on 3D perovskites, mainly attributed to their poor charge transport. Herein, a simple yet universal method for controlling the quality of RPP films by a synergistic effect of two additives in the precursor solution is presented. RPP films achieved by this method show (a) high quality with uniform morphology, enhanced crystallinity, and reduced density of sub-bandgap states, (b) vertically oriented perovskite frameworks that facilitate efficient charge transport, and (c) type-II band alignment that favors self-driven charge separation. Consequently, a hysteresis-free RPP solar cell with a power conversion efficiency exceeding 12%, which is much higher than that of the control device (1.5%), is achieved. The findings will spur new developments in the fabrication of high-quality, aligned, and graded RPP films essential for realizing efficient and stable perovskite solar cells. Solar CellsOrganic-inorganic halide perovskites, such as MAPbI 3 (MA = CH 3 NH 3 ), FAPbI 3 (FA = CH(NH 2 ) 2 ), and their mixed cation analogues, have emerged as promising light absorbers for solar cells due to their superior photophysical properties and
Summary Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age‐matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.
Conventional metal-organic framework (MOF) powders have periodic micro/mesoporous crystalline architectures tuned by their three-dimensional coordination of metal nodes and organic linkers. To add practical macroscopic shapeability and extrinsic hierarchical porosity, fibrous MOF aerogels were produced by synthesizing MOF crystals on the template of TEMPO-cellulose nanofibrils. Cellulose nanofibrils not only offered extrinsic porosities and mechanical flexibility for the resultant MOF aerogels, but also shifted the balance of nucleation and growth for synthesizing smaller MOF crystals, and further decreased their aggregation possibilities. Thanks to their excellent shapeability, hierarchical porosity up to 99%, and low density below 0.1 g/cm, these MOF aerogels could make the most of their pores and accessible surface areas for higher adsorption capacity and rapid adsorption kinetics of different molecules, in sharp contrast to conventional MOF powders. Thus, this scalable and low-cost production pathway is able to convert MOF powders into a shapeable and flexible form and thereby extend their applications in more broad fields, for example, adapting a conventional filtration setup.
Nanometerization of liquid metal in organic systems can facilitate deposition of liquid metals onto substrates and then recover its conductivity through sintering. Although having broader potential applications, producing stable aqueous inks of liquid metals keeps challenging because of rapid oxidation of liquid metal when exposing to water and oxygen. Here, a biocompatible aqueous ink is produced by encapsulating alloy nanodroplets of gallium and indium (EGaIn) into microgels of marine polysaccharides. During sonicating bulk EGaIn in aqueous alginate solution, alginate not only facilitates the downsizing process via coordination of their carboxyl groups with Ga ions but also forms microgel shells around EGaIn droplets. Due to the deceasing oxygen-permeability of microgel shells, aqueous ink of EGaIn nanodroplets can maintain colloidal and chemical stability for a period of >7 d. Crosslinked alginate-gel with tunable thickness can retard the generation and release of toxic cations, thereby affording high biocompatibility. The soft alginate shells also enable to recover electric conductivity of EGaIn layers by "mechanical sintering" for applications in microcircuits, electric-thermal actuators, and wearable sensors, offering huge potential for electronic tattoos, artificial limbs, electric skins, etc.
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