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The evolution of real-time medical diagnostic tools such as angiography and computer tomography from radiography based on photographic plates was enabled by the development of integrated solid-state X-ray photon detectors made from conventional solid-state semiconductors. Recently, for optoelectronic devices operating in the visible and near-infrared spectral regions, solution-processed organic and inorganic semiconductors have also attracted a great deal of attention. Here, we demonstrate a possibility to use such inexpensive semiconductors for the sensitive detection of X-ray photons by direct photon-to-current conversion. In particular, methylammonium lead iodide perovskite (CH 3 NH 3 PbI 3 ) offers a compelling combination of fast photoresponse and a high absorption cross-section for X-rays, owing to the heavy Pb and I atoms. Solution-processed photodiodes as well as photoconductors are presented, exhibiting high values of X-ray sensitivity (up to 25 μC mGy air −1  cm −3 ) and responsivity (1.9 × 10 4  carriers/photon), which are commensurate with those obtained by the current solid-state technology. Solid-state X-ray detectors have enabled real-time diagnostics as well as reduced patient dose. Now researchers have shown that potentially inexpensive perovskites can be used for efficient X-ray imaging.

The performance of organic solar cells is determined by the delicate, meticulously optimized bulk-heterojunction microstructure, which consists of finely mixed and relatively separated donor/acceptor regions. Here we demonstrate an abnormal strong burn-in degradation in highly efficient polymer solar cells caused by spinodal demixing of the donor and acceptor phases, which dramatically reduces charge generation and can be attributed to the inherently low miscibility of both materials. Even though the microstructure can be kinetically tuned for achieving high-performance, the inherently low miscibility of donor and acceptor leads to spontaneous phase separation in the solid state, even at room temperature and in the dark. A theoretical calculation of the molecular parameters and construction of the spinodal phase diagrams highlight molecular incompatibilities between the donor and acceptor as a dominant mechanism for burn-in degradation, which is to date the major short-time loss reducing the performance and stability of organic solar cells. Li et al . study degradation in organic photovoltaics from a morphological perspective. They find that donor and acceptor phases undergo excessive demixing via spinodal decomposition resulting in a reduction of charge generation. Demixing is due to the inherently low miscibility of both materials.

A major bottleneck delaying the further commercialization of thin-film solar cells based on hybrid organohalide lead perovskites is interface loss in state-of-the-art devices. We present a generic interface architecture that combines solution-processed, reliable, and cost-efficient hole-transporting materials without compromising efficiency, stability, or scalability of perovskite solar cells. Tantalum-doped tungsten oxide (Ta-WOₓ)/conjugated polymer multilayers offer a surprisingly small interface barrier and form quasi-ohmic contacts universally with various scalable conjugated polymers. In a simple device with regular planar architecture and a self-assembled monolayer, Ta-WOₓ–doped interface–based perovskite solar cells achieve maximum efficiencies of 21.2% and offer more than 1000 hours of light stability. By eliminating additional ionic dopants, these findings open up the entire class of organics as scalable hole-transporting materials for perovskite solar cells.

Medical X-ray imaging requires cost-effective and high-resolution flat-panel detectors for the energy range between 20 and 120 keV. Solution-processed photodetectors provide the opportunity to fabricate detectors with a large active area at low cost. Here, we present a disruptive approach that improves the resolution of such detectors by incorporating terbium-doped gadolinium oxysulfide scintillator particles into an organic photodetector matrix. The X-ray induced light emission from the scintillators is absorbed within hundreds of nanometres, which is negligible compared with the pixel size. Hence, optical crosstalk, a limiting factor in the resolution of scintillator-based X-ray detectors, is minimized. The concept is validated with a 256 × 256 pixel detector with a resolution of 4.75 lp mm −1 at a MTF = 0.2, significantly better than previous stacked scintillator-based flat-panel detectors. We achieved a resolution that proves the feasibility of solution-based detectors in medical applications. Time-resolved electrical characterization showed enhanced charge carrier mobility with increased scintillator filling, which is explained by morphological changes. A 256 × 256 pixel scintillator-based X-ray detector that improves resolution by limiting optical cross-talk is made using terbium-doped gadolinium oxysulfide scintillator particles in an organic photodetector matrix.

The evolution of real-time medical diagnostic tools such as angiography and computer tomography from radiography based on photographic plates was enabled by the development of integrated solid-state X-ray photon detectors, based on conventional solid-state semiconductors. Recently, for optoelectronic devices operating in the visible and near infrared spectral regions, solution-processed organic and inorganic semiconductors have also attracted immense attention. Here we demonstrate a possibility to use such inexpensive semiconductors for sensitive detection of X-ray photons by direct photon-to-current conversion. In particular, methylammonium lead iodide perovskite (CH NH PbI ) offers a compelling combination of fast photoresponse and a high absorption cross-section for X-rays, owing to the heavy Pb and I atoms. Solution processed photodiodes as well as photoconductors are presented, exhibiting high values of X-ray sensitivity (up to 25 µC mGy cm ) and responsivity (1.9×10 carriers/photon), which are commensurate with those obtained by the current solid-state technology.

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparum circumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO’s preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development. Isolation and optimization of antibodies targeting the malaria parasite may offer the potential for immediate protection as a prophylactic intervention to prevent severe disease.

Fabrication of surfactant-modified DNA thin films with high uniformity, specifically DNA–CTMA, has been well considered via drop-casting and spin-coating techniques. However, the fabrication of thin films with pure DNA has not been sufficiently studied. We characterize the uniformity of thin films from aqueous salmon DNA solutions mixed with ethanol, methanol, isopropanol, and acetone. Measurements of thickness and macroscopic uniformity are made via a focused-beam ellipsometer. We discuss important parameters for optimum uniformity and note what the effects of solvent modifications are. We find that methanol- and ethanol-added solutions provide optimal fabrication methods, which more consistently produce high degrees of uniformity with film thickness ranging from 20 to 200 nm adjusted by DNA concentration and the physical parameters of spin-coating methods.

PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non-PDE4 activity in human hearts compared to rodents. As a consequence, the effect of PDE4 inactivation is different in rodents and humans. PDE4 inhibition leads to increased phosphorylation of virtually all PKA substrates in mouse cardiomyocytes, but increased phosphorylation of only a restricted number of proteins in human cardiomyocytes. Our findings suggest that PDE4s have a similar role in the local regulation of cAMP signaling in rodent and human heart. However, inhibition of PDE4 has ‘global’ effects on cAMP signaling only in rodent hearts, as PDE4 comprises a large fraction of the total cardiac PDE activity in rodents but not in humans. These differences may explain the distinct pharmacological effects of PDE4 inhibition in rodent and human hearts.

BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) antibody measures associated with protection from controlled human malaria infection (CHMI). Here, we tested the protection-predicting capability of these measures in independent CHMI studies.METHODSVaccine-induced total serum antibody (immunoglobulins, Igs) and subclass antibody (IgG1 and IgG3) responses were measured by biolayer interferometry and the binding antibody multiplex assay, respectively. Immune responses were compared between protected and nonprotected vaccinees using univariate and multivariate logistic regression.RESULTSBlinded prediction analysis showed that 5 antibody binding measures, including magnitude-avidity composite of serum Ig specific for PfCSP, major NANP repeats and N-terminal junction, and PfCSP- and NANP-specific IgG1 subclass magnitude, had good prediction accuracy (area under the receiver operating characteristic curves [ROC AUC] > 0.7) in at least 1 trial. Furthermore, univariate analysis showed a significant association between these antibody measures and protection (odds ratios 2.6-3.1). Multivariate modeling of combined data from 3 RTS,S CHMI trials identified the combination of IgG1 NANP binding magnitude plus serum NANP and N-junction Ig binding magnitude-avidity composite as the best predictor of protection (95% confidence interval for ROC AUC 0.693-0.834).CONCLUSIONThese results reinforce our previous findings and provide a tool for predicting protection in future trials.TRIAL REGISTRATIONClinicalTrials.gov NCT03162614, NCT03824236, NCT01366534, and NCT01857869.FUNDINGThis study was supported by Bill & Melinda Gates Foundation's Global Health-Discovery Collaboratory grants (INV-008612 and INV-043419) to GDT.

β-Adrenergic receptors (β-ARs) enhance cardiac contractility by increasing cAMP levels and activating PKA. PKA increases Ca²⁺-induced Ca²⁺ release via phosphorylation of L-type Ca²⁺ channels (LTCCs) and ryanodine receptor 2. Multiple cyclic nucleotide phosphodiesterases (PDEs) regulate local cAMP concentration in cardiomyocytes, with PDE4 being predominant for the control of β-AR-dependent cAMP signals. Three genes encoding PDE4 are expressed in mouse heart: Pde4a, Pde4b, and Pde4d. Here we show that both PDE4B and PDE4D are tethered to the LTCC in the mouse heart but that β-AR stimulation of the L-type Ca²⁺ current (ICa,L) is increased only in Pde4b-/- mice. A fraction of PDE4B colocalized with the LTCC along T-tubules in the mouse heart. Under β-AR stimulation, Ca²⁺ transients, cell contraction, and spontaneous Ca²⁺ release events were increased in Pde4b-/- and Pde4d-/- myocytes compared with those in WT myocytes. In vivo, after intraperitoneal injection of isoprenaline, catheter-mediated burst pacing triggered ventricular tachycardia in Pde4b-/- mice but not in WT mice. These results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa,L during β-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of Ca²⁺-induced Ca²⁺ release in cardiomyocytes.