Elliswoods7553

In a phase 1 randomized, single-center clinical trial, inactivated influenza virus vaccine delivered through dissolvable microneedle patches (MNPs) was found to be safe and immunogenic. Here, we compare the humoral and cellular immunologic responses in a subset of participants receiving influenza vaccination by MNP to the intramuscular (IM) route of administration. We collected serum, plasma, and peripheral blood mononuclear cells in 22 participants up to 180 days post-vaccination. Hemagglutination inhibition (HAI) titers and antibody avidity were similar after MNP and IM vaccination, even though MNP vaccination used a lower antigen dose. MNPs generated higher neuraminidase inhibition (NAI) titers for all three influenza virus vaccine strains tested and triggered a larger percentage of circulating T follicular helper cells (CD4 + CXCR5 + CXCR3 + ICOS + PD-1+) compared to the IM route. Our study indicates that inactivated influenza virus vaccination by MNP produces humoral and cellular immune response that are similar or greater than IM vaccination.Photoelectrochemical catalysis is an attractive way to provide direct hydrogen production from solar energy. However, solar conversion efficiencies are hindered by the fact that light harvesting has so far been of limited efficiency in the near-infrared region as compared to that in the visible and ultraviolet regions. Here we introduce near-infrared-active photoanodes that feature lattice-matched morphological hetero-nanostructures, a strategy that improves energy conversion efficiency by increasing light-harvesting spectral range and charge separation efficiency simultaneously. Specifically, we demonstrate a near-infrared-active morphological heterojunction comprised of BiSeTe ternary alloy nanotubes and ultrathin nanosheets. The heterojunction's hierarchical nanostructure separates charges at the lattice-matched interface of the two morphological components, preventing further carrier recombination. As a result, the photoanodes achieve an incident photon-to-current conversion efficiency of 36% at 800 nm in an electrolyte solution containing hole scavengers without a co-catalyst.Molecular single cell analyses provide insights into physiological and pathological processes. Here, in a stepwise approach, we first evaluate 19 protocols for single cell small RNA sequencing on MCF7 cells spiked with 1 pg of 1,006 miRNAs. Second, we analyze MCF7 single cell equivalents of the eight best protocols. Third, we sequence single cells from eight different cell lines and 67 circulating tumor cells (CTCs) from seven SCLC patients. Altogether, we analyze 244 different samples. We observe high reproducibility within protocols and reads covered a broad spectrum of RNAs. For the 67 CTCs, we detect a median of 68 miRNAs, with 10 miRNAs being expressed in 90% of tested cells. Enrichment analysis suggested the lung as the most likely organ of origin and enrichment of cancer-related categories. Even the identification of non-annotated candidate miRNAs was feasible, underlining the potential of single cell small RNA sequencing.Self-healability is essential for supercapacitors to improve their reliability and lifespan when powering the electronics. However, the lack of a universal healing mechanism leads to low capacitive performance and unsatisfactory intelligence. Here, we demonstrate a multi-responsive healable supercapacitor with integrated configuration assembled from magnetic Fe3O4@Au/polyacrylamide (MFP) hydrogel-based electrodes and electrolyte and Ag nanowire films as current collectors. Beside a high mechanical strength, MFP hydrogel exhibits fast optical and magnetic healing properties arising from distinct photothermal and magneto-thermal triggered interfacial reconstructions. selleck By growing electroactive polypyrrole nanoparticles into MFP framework as electrodes, the assembled supercapacitor exhibits triply-responsive healing performance under optical, electrical and magnetic stimuli. Notably, the device delivers a highest areal capacitance of 1264 mF cm-2 among the reported healable supercapacitors and restores ~ 90% of initial capacitances over ten healing cycles. These prominent performance advantages along with the facile device-assembly method make this emerging supercapacitor highly potential in the next-generation electronics.Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes.Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.The rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features.Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions.Unmasking the decision making process of machine learning models is essential for implementing diagnostic support systems in clinical practice. Here, we demonstrate that adversarially trained models can significantly enhance the usability of pathology detection as compared to their standard counterparts. We let six experienced radiologists rate the interpretability of saliency maps in datasets of X-rays, computed tomography, and magnetic resonance imaging scans. Significant improvements are found for our adversarial models, which are further improved by the application of dual-batch normalization. Contrary to previous research on adversarially trained models, we find that accuracy of such models is equal to standard models, when sufficiently large datasets and dual batch norm training are used. To ensure transferability, we additionally validate our results on an external test set of 22,433 X-rays. These findings elucidate that different paths for adversarial and real images are needed during training to achieve state of the art results with superior clinical interpretability.Earth's deep carbon cycle affects atmospheric CO2, climate, and habitability. Owing to the extreme solubility of CaCO3, aqueous fluids released from the subducting slab could extract all carbon from the slab. However, recycling efficiency is estimated at only around 40%. Data from carbonate inclusions, petrology, and Mg isotope systematics indicate Ca2+ in carbonates is replaced by Mg2+ and other cations during subduction. Here we determined the solubility of dolomite [CaMg(CO3)2] and rhodochrosite (MnCO3), and put an upper limit on that of magnesite (MgCO3) under subduction zone conditions. Solubility decreases at least two orders of magnitude as carbonates become Mg-rich. This decreased solubility, coupled with heterogeneity of carbon and water subduction, may explain discrepancies in carbon recycling estimates. Over a range of slab settings, we find aqueous dissolution responsible for mobilizing 10 to 92% of slab carbon. Globally, aqueous fluids mobilise [Formula see text]% ([Formula see text] Mt/yr) of subducted carbon from subducting slabs.Capping ligands are crucial to synthesizing colloidal nanoparticles with functional properties. However, the synergistic effect between different ligands and their distribution on crystallographic surfaces of nanoparticles during colloidal synthesis is still unclear despite powerful spectroscopic techniques, due to a lack of direct imaging techniques. In this study, atom probe tomography is adopted to investigate the three-dimensional atomic-scale distribution of two of the most common types of these ligands, cetrimonium (C19H42N) and halide (Br and Cl) ions, on Pd nanoparticles. The results, validated using density functional theory, demonstrate that the Br anions adsorbed on the nanoparticle surfaces promote the adsorption of the cetrimonium cations through electrostatic interactions, stabilizing the Pd 111 facets. In contrast, the Cl anions are not strongly adsorbed onto the Pd surfaces. The high density of adsorbed cetrimonium cations for Br anion additions results in the formation of multiple-twinned nanoparticles with superior oxidation resistance.