Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight ...junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.
A likely important feature of the poorly understood aerosol‐cloud interactions over the Southern Ocean (SO) is the dominant role of sea spray aerosol, versus terrestrial aerosol. Ice nucleating ...particles (INPs), or particles required for heterogeneous ice nucleation, present over the SO have not been studied in several decades. In this study, boundary layer aerosol properties and immersion freezing INP number concentrations (nINPs) were measured during a ship campaign that occurred south of Australia (down to 53°S) in March–April 2016. Ocean surface chlorophyll a concentrations ranged from 0.11 to 1.77 mg/m3, and nINPs were a factor of 100 lower than historical surveys, ranging from 0.38 to 4.6 m−3 at −20 °C. The INP population included organic heat‐stable material, with contributions from heat‐labile material. Lower INP source potentials of SO seawater samples compared to Arctic seawater were consistent with lower ice nucleating site densities in this study compared to north Atlantic air masses.
Plain Language Summary
The Southern Ocean is known for a prevalence of clouds that contain both liquid and ice, which are one of the most poorly understood cloud regimes in the climate system. A large gap in understanding important processes in these clouds is a lack of knowledge regarding particles (e.g., sea spray) required for forming ice crystals, termed ice nucleating particles. In a ship‐based monthlong field study, several instruments were deployed in efforts to characterize the ice nucleating particles present over the Southern Ocean for the first time in over four decades. Abundances of ice nucleating particles throughout the voyage were extremely low compared to other ocean regions, and concentrations were 2 orders of magnitude lower than the most recent survey conducted in the 1970s. We report that the ocean‐derived ice nucleating particles observed in this study were organic in nature, supporting a hypothesized link between ice nucleating particles and organic particles associated with phytoplankton blooms. The data from this study provide a desperately needed benchmark for constraining the number of ice crystals that may form in the remote and poorly understood clouds occurring over the Southern Ocean.
Key Points
Number concentrations of ice nucleating particles over the Southern Ocean in March 2016 were a factor of 100 lower than historical surveys
The ice nucleating particle source strength of Southern Ocean seawater was lower than previous measurements in northern hemisphere seawater
Ice nucleation site densities were lower over the Southern Ocean compared to measurements of pristine air masses from other ocean basins
Summary
Aerosol‐generating procedures such as tracheal intubation and extubation pose a potential risk to healthcare workers because of the possibility of airborne transmission of infection. Detailed ...characterisation of aerosol quantities, particle size and generating activities has been undertaken in a number of simulations but not in actual clinical practice. The aim of this study was to determine whether the processes of facemask ventilation, tracheal intubation and extubation generate aerosols in clinical practice, and to characterise any aerosols produced. In this observational study, patients scheduled to undergo elective endonasal pituitary surgery without symptoms of COVID‐19 were recruited. Airway management including tracheal intubation and extubation was performed in a standard positive pressure operating room with aerosols detected using laser‐based particle image velocimetry to detect larger particles, and spectrometry with continuous air sampling to detect smaller particles. A total of 482,960 data points were assessed for complete procedures in three patients. Facemask ventilation, tracheal tube insertion and cuff inflation generated small particles 30–300 times above background noise that remained suspended in airflows and spread from the patient’s facial region throughout the confines of the operating theatre. Safe clinical practice of these procedures should reflect these particle profiles. This adds to data that inform decisions regarding the appropriate precautions to take in a real‐world setting.
The development of bright free-electron lasers (FEL) has revolutionized our ability to create and study matter in the high-energy-density (HED) regime. Current diagnostic techniques have been ...successful in yielding information on fundamental thermodynamic plasma properties, but provide only limited or indirect information on the detailed quantum structure of these systems, and on how it is affected by ionization dynamics. Here we show how the valence electronic structure of solid-density nickel, heated to temperatures of around 10 of eV on femtosecond timescales, can be probed by single-shot resonant inelastic x-ray scattering (RIXS) at the Linac Coherent Light Source FEL. The RIXS spectrum provides a wealth of information on the HED system that goes well beyond what can be extracted from x-ray absorption or emission spectroscopy alone, and is particularly well suited to time-resolved studies of electronic-structure dynamics.
In this paper, the deformation mechanisms of a Fe–2.25%Cr–1%Mo (P22) steel are studied after tensile tests at room temperature (RT) and 550 °C (HT), creep-fatigue tests at 550 °C and stress ...relaxation test at 550 °C (HTSR). The RT, HT and HTSR tests produced permanent strain of about 2.5% by different processes. Deformation features such as the orientation of the grains, local misorientation, grain boundary type and distribution, etc., were characterized using electron backscatter diffraction. Transmission electron microscopy was done subsequently to obtain greater insight into the dislocation substructures. The as-received sample had a ferritic–bainitic microstructure, and a large amount of local misorientation was found in the bainite, indicating plastic strain due to phase transformation. After tensile strain to 2.5% at room temperature, the dislocations formed very small substructures (~100–200 nm) in the ferrite grains, and most of the retained plastic strain seemed to be concentrated in the bainite after deformation. Both the ferrite and bainite showed much lower local misorientation and dislocation wall content after a tensile test to 2.5% strain at 550 °C. Compared to the RT tensile sample, after creep-fatigue at 550 °C, the substructures in ferrite opened up considerably and formed small-angle grain boundaries, with clean areas as large as 20–25 μm. After stress relaxation at 550 °C, the ferrite displayed even less substructure, while the bainite seemed to have greater amounts of local misorientation than in the creep-fatigue case. However, the degree of misorientation was less pronounced than in the room temperature tensile case. These results have been discussed with respect to the causes behind the phenomena observed herein and their possible effects on mechanical behaviour.
Graphical Abstract
The spread of respiratory diseases via aerosol particles in indoor settings is of significant concern. The SARS-CoV-2 virus has been found to spread widely in confined enclosures like hotels, ...hospitals, cruise ships, prisons, and churches. Particles exhaled from a person indoors can remain suspended long enough for increasing the opportunity for particles to spread spatially. Careful consideration of the ventilation system is essential to minimise the spread of particles containing infectious pathogens. Previous studies have shown that indoor airflow induced by opened windows would minimise the spread of particles. However, how outdoor airflow through an open window influences the indoor airflow has not been considered. The aim of this study is to provide a clear understanding of the indoor particle spread across multiple rooms, in a situation similar to what is found in quarantine hotels and cruise ships, using a combination of HVAC (Heating, Ventilation and Air-Conditioning) ventilation and an opening window. Using a previously validated mathematical model, we used 3D CFD (computational fluid dynamics) simulations to investigate to what extent different indoor airflow scenarios contribute to the transport of a single injection of particles (1.3μm) in a basic 3D multi-room indoor environment. Although this study is limited to short times, we demonstrate that in certain conditions approximately 80% of the particles move from one room to the corridor and over 60% move to the nearby room within 5 to 15 s. Our results provide additional information to help identifying relevant recommendations to limit particles from spreading in enclosures.
•CFD simulations show that an opened window has a dominant effect in the indoor settings.•An open window contributes to the transport of particles across multiple rooms.•Within seconds, exhaled particles can spread to the corridor and opposite room.•Simulation outcomes provide knowledge of lowering indoor particle spread.
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