SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not ...significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new variants of concern (VOCs). In this study, we evaluated the immunogenicity and efficacy of a mucosally-delivered, non-replicating, adenovirus type 5-vectored vaccine that expresses the spike (S) gene of Wuhan (rAd5-S-Wuhan), delta (rAd5-S-delta), or omicron (rAd5-S-omicron) SARS-CoV-2 VOCs. Hamsters were immunized with these vaccines intranasally prior to challenge with omicron or delta variants. Additionally, one group was vaccinated by oral gavage with rAd5-S-Wuhan prior to challenge with the delta variant. Both intranasal and oral administration of rAd5-S-Wuhan generated cross-reactive serum IgG and mucosal IgA to all variant spike and RBD proteins tested. rAd5-S-omicron and rAd5-S-delta additionally elicited cross-reactive antibodies, though rAd5-S-omicron had significantly lower binding antibody levels except against its matched antigens. Two weeks after the final vaccination, hamsters were challenged with a SARS-CoV-2 variant; omicron or delta. Whether matched to the challenge or with rAd5-S-Wuhan, all vaccines protected hamsters from weight loss and lung pathology caused by challenge and significantly reduced viral shedding compared to placebo. Vaccination with rAd5-S-Wuhan provided significant protection, although there was an improved reduction in shedding and disease pathology in groups protected by the matched VOC vaccines. Nevertheless, Wuhan-based vaccination elicited the most cross-reactive antibody responses generally. Overall, heterologous vaccination
mucosal routes may be advantageous for second-generation vaccines.
Germanium–tin alloy nanowires hold promise as silicon-compatible optoelectronic elements with the potential to achieve a direct band gap transition required for efficient light emission. In contrast ...to Ge1–x Sn x epitaxial thin films, free-standing nanowires deposited on misfitting germanium or silicon substrates can avoid compressive, elastic strains that inhibit formation of a direct gap. We demonstrate strong room temperature photoluminescence, consistent with band edge emission from both Ge core nanowires, elastically strained in tension, and the almost unstrained Ge1–x Sn x shells grown around them. Low-temperature chemical vapor deposition of these core-shell structures was achieved using standard precursors, resulting in Sn incorporation that significantly exceeds the bulk solubility limit in germanium.
RNA is a central component of gene-silencing pathways that regulate diverse cellular processes. In the fission yeast Schizosaccharomyces pombe, an RNA-based mechanism represses meiotic gene ...expression during vegetative growth. This pathway depends on the zinc finger protein Red1, which is required to degrade meiotic mRNAs as well as to target histone H3 lysine 9 (H3K9) methylation, a repressive chromatin mark, to a subset of meiotic genes. However, the mechanism of Red1 function is unknown. Here we use affinity purification and mass spectrometry to identify a Red1-containing nuclear RNA silencing (NURS) complex. In addition to Red1, this complex includes the Mtl1, Red5, Ars2, Rmn1, and Iss10 proteins and associates with several other complexes that are involved in either signaling or mediating RNA silencing. By analyzing the effects of gene knockouts and inducible knockdown alleles, we show that NURS subunits regulate RNA degradation and H3K9 methylation at meiotic genes. We also identify roles for individual NURS subunits in interactions with Mmi1, an RNA-binding protein that marks meiotic RNAs for destruction, and the nuclear exosome RNA degradation complex. Finally, we show that the levels of H3K9 methylation at meiotic genes are not sufficient to restrict RNA polymerase II access or repress gene expression during vegetative growth. Our results demonstrate that Red1 partners with other proteins to silence meiotic gene expression at the post-transcriptional level. Conservation of a NURS-like complex in human cells suggests that this pathway plays an ancient and fundamental role in RNA silencing.
Rapid eye movement (REM) sleep constitutes a distinct “third state” of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically ...transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.
Japan is in the midst of a demographic transition that is both rapid and large by international standards. As recently as 1990 Japan had the youngest population among the Group of 6 large, developed ...countries. However, the combined effects of aging of the baby-boomer generation and low fertility rates have produced very rapid aging. Japan now finds itself with the oldest population among the Group of 6 and its population will continue to age at a rapid pace in future years. Aging is already placing a burden on government finances and Japan׳s ability to confront the negative fiscal implications of future aging is constrained by its very high debt–GDP ratio. We find that Japan faces a severe fiscal crisis if remedial action is not undertaken soon and analyze alternative strategies for correcting Japan׳s fiscal imbalances.
► The amount of hydrogen recovery (85–90%) with EHS is higher than PSA. ► SOFC electrical efficiency of 48.8% (LHV) and best overall CHHP efficiency of 85.2% is achievable. ► Operating the system to ...produce excess hydrogen increases the CHHP efficiency for all concepts. ► Cost of distributed SOFC H
2 production (4.4
$
kg
−1) is on par with other distributed H
2 production technologies. ► ‘Spark spreads’ of >five offer near-zero or negative H
2 production costs for distributed SOFC plants.
This work focuses on the design and performance estimation of a methane-fueled, 1 MW SOFC combined heat, hydrogen, and power (CHHP) system operating at steady-state. Two methods of hydrogen purification and recovery from the SOFC tail-gas are analyzed: pressure swing adsorption (PSA) and electrochemical hydrogen separation (EHS). The SOFC electrical efficiency at rated power is estimated at 48.8% (LHV) and the overall CHHP efficiency is 85.2% (LHV) for the EHS design concept. The EHS energy requirement of 2.7
kWh
kg
−1 H
2 is found to be about three times lower than PSA in this system. Operating the system to produce additional hydrogen by flowing excess methane into the SOFC subsystem results in increased efficiency for both of the hydrogen separation design concepts. An economic analysis indicates that the expected cost of SOFC-based distributed hydrogen production (4.4
$
kg
−1) is on par with other distributed hydrogen production technologies, such as natural gas reforming, electrolysis, and molten carbonate fuel cell CHHP systems. The study illustrates that ‘spark spreads’ (cost of electricity in ¢
kWh
−1 minus cost of natural gas in $
MMBtu
−1) of five or more offer near-zero or negative hydrogen production costs for distributed SOFC CHHP plants with total installed capital costs near 3950
$
kW.
One of the main roles of the lipid layer (LL) of the tear film (TF) is to help prevent evaporation of the aqueous layer (AL). The LL thickness, composition, and structure all contribute to its ...barrier function. It is believed that the lipid layer is primarily nonpolar with a layer of polar lipids at the LL/AL interface. There is evidence that the nonpolar region of the LL may have liquid crystalline characteristics. We investigate the structure and function of the LL via a model of the tear film with two layers, using extensional flow of a nematic liquid crystal for the LL and shear-dominated flow of a Newtonian AL. Evaporation is taken into account and is affected by the LL thickness, internal arrangement of its rod-like molecules, and external conditions. We conduct a detailed parameter study with a focus on the evaporative resistance parameter, the Marangoni number, and primary liquid crystal parameters including the Leslie viscosities and director angle. This new model responds similarly to previous Newtonian models in some respects; however, incorporating internal structure via the orientation of the liquid crystal molecules affects both evaporation and flow. As a result, we see new effects on TF dynamics and breakup.
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