α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn ...fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
Linking human behavior to resting-state brain function is a central question in systems neuroscience. In particular, the functional timescales at which different types of behavioral factors are ...encoded remain largely unexplored. The behavioral counterparts of static functional connectivity (FC), at the resolution of several minutes, have been studied but behavioral correlates of dynamic measures of FC at the resolution of a few seconds remain unclear. Here, using resting-state fMRI and 58 phenotypic measures from the Human Connectome Project, we find that dynamic FC captures task-based phenotypes (e.g., processing speed or fluid intelligence scores), whereas self-reported measures (e.g., loneliness or life satisfaction) are equally well explained by static and dynamic FC. Furthermore, behaviorally relevant dynamic FC emerges from the interconnections across all resting-state networks, rather than within or between pairs of networks. Our findings shed new light on the timescales of cognitive processes involved in distinct facets of behavior.
Abstract
Severe events of wintertime particulate air pollution in Beijing (winter haze) are associated with high relative humidity (RH) and fast production of particulate sulfate from the oxidation ...of sulfur dioxide (SO
2
) emitted by coal combustion. There has been considerable debate regarding the mechanism for SO
2
oxidation. Here we show evidence from field observations of a haze event that rapid oxidation of SO
2
by nitrogen dioxide (NO
2
) and nitrous acid (HONO) takes place, the latter producing nitrous oxide (N
2
O). Sulfate shifts to larger particle sizes during the event, indicative of fog/cloud processing. Fog and cloud readily form under winter haze conditions, leading to high liquid water contents with high pH (>5.5) from elevated ammonia. Such conditions enable fast aqueous-phase oxidation of SO
2
by NO
2
, producing HONO which can in turn oxidize SO
2
to yield N
2
O.This mechanism could provide an explanation for sulfate formation under some winter haze conditions.
•Composite desiccants were prepared for desiccant coated heat exchanger (DCHE).•Texture properties of composite samples were different from pure hosts.•Composite desiccants had enhanced sorption ...kinetics and isotherms.•Enhanced dehumidification capacity was evaluated using composite materials in DCHE.
A DCHE (desiccant coated heat exchanger) is a novel solid desiccant cooling component with desiccant coated onto the surface of a fin-tube heat exchanger. In the paper, carbon based composite desiccants were developed and studied for DCHE systems. Composite desiccants were fabricated by impregnating LiCl into pores of activated carbon and activated carbon fiber. Due to impregnated salt, composite desiccants were found to have smaller surface area and pore volume. Sorption isotherms were measured and simulated based on Polanyi potential theory. Water sorption isotherms showed that composite desiccants possessed enhanced sorption quantity. Sorption kinetics was also investigated and fitted with the linear driving model. Composite desiccants showed higher dynamic water uptakes and reasonable rate coefficients. Finally, to predict dehumidification performance of composite desiccants in DCHE systems, a mathematical model was built. Simulation results showed that composite desiccant coated DCHEs can remove more moisture from the process air.
This work aims to present our current best physical understanding of common-envelope evolution (CEE). We highlight areas of consensus and disagreement, and stress ideas which should point the way ...forward for progress in this important but long-standing and largely unconquered problem. Unusually for CEE-related work, we mostly try to avoid relying on results from population synthesis or observations, in order to avoid potentially being misled by previous misunderstandings. As far as possible we debate all the relevant issues starting from physics alone, all the way from the evolution of the binary system immediately before CEE begins to the processes which might occur just after the ejection of the envelope. In particular, we include extensive discussion about the energy sources and sinks operating in CEE, and hence examine the foundations of the standard energy formalism. Special attention is also given to comparing the results of hydrodynamic simulations from different groups and to discussing the potential effect of initial conditions on the differences in the outcomes. We compare current numerical techniques for the problem of CEE and also whether more appropriate tools could and should be produced (including new formulations of computational hydrodynamics, and attempts to include 3D processes within 1D codes). Finally we explore new ways to link CEE with observations. We compare previous simulations of CEE to the recent outburst from V1309 Sco, and discuss to what extent post-common-envelope binaries and nebulae can provide information, e.g. from binary eccentricities, which is not currently being fully exploited.
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered ...participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.
Asymptomatic patients, together with those with mild symptoms of coronavirus disease 2019 (COVID-19), may play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...transmission. However, the dynamics of virus shedding during the various phases of the clinical course of COVID-19 remains unclear at this stage.
A total of 18 patients found to be positive for SARS-CoV-2 infection by real-time reverse transcription PCR (RT-PCR) assay and admitted to Chongqing University Central Hospital between 29 January and 5 February 2020 were enrolled into this study. Medical data, pulmonary computed tomographic (CT) scan images and RT-PCR results were periodically collected during the patients' hospital stay. All participants were actively followed up for 2 weeks after discharge.
A total of nine (50%) asymptomatic patients and nine (50%) patients with mild symptoms of COVID-19 were identified at admission. Six patients (66.7%) who were asymptomatic at admission developed subjective symptoms during hospitalization and were recategorized as being presymptomatic. The median duration of virus shedding was 11.5, 28 and 31 days for presymptomatic, asymptomatic and mildly symptomatic patients, separately. Seven patients (38.9%) continued to shed virus after hospital discharge. During the convalescent phase, detectable antibodies to SARS-CoV-2 and RNA were simultaneously observed in five patients (27.8%).
Long-term virus shedding was documented in patients with mild symptoms and in asymptomatic patients. Specific antibody production to SARS-CoV-2 may not guarantee virus clearance after discharge. These observations should be considered when making decisions regarding clinical and public health, and when considering strategies for the prevention and control of SARS-CoV-2 infection.
Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine ...efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.
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