The synergy between free electrons and light has recently been leveraged to reach an impressive degree of simultaneous spatial and spectral resolution, enabling applications in microscopy and quantum ...optics. However, the required combination of electron optics and light injection into the spectrally narrow modes of arbitrary specimens remains a challenge. Here, we demonstrate microelectronvolt spectral resolution with a sub-nanometer probe of photonic modes with quality factors as high as 10
. We rely on mode matching of a tightly focused laser beam to whispering gallery modes to achieve a 10
-fold increase in light-electron coupling efficiency. By adapting the shape and size of free-space optical beams to address specific physical questions, our approach allows us to interrogate any type of photonic structure with unprecedented spectral and spatial detail.
To compare thermography with ultrasonography and clinical joint assessment in patients with rheumatoid arthritis (RA).
Thermography and ultrasonography (power Doppler (PD) and grey-scale (GS) joint ...inflammation scored semi-quantitatively 0–3) were performed sequentially on both hands of 37 RA patients. Using generalised estimating equations analysis, (a) thermographic parameters (TP) were compared between joints based on their PD and GS joint inflammation positivity/negativity status, while (b) TP and ultrasound-detected joint inflammation were compared between joints categorised by their clinical swelling/tenderness status.
Comparing PD positive versus negative joints, the differences in mean values (95% CI) for TP including maximum (Tmax), minimum (Tmin), average (Tavg), and Tmax minus Tmin (Tmax–min) temperatures (in °C) were 1.37 (0.86, 1.87), 0.91 (0.46, 1.36), 1.16 (0.67, 1.64), and 0.46 (0.28, 0.64), respectively. Comparing GS positive versus negative joints, the corresponding results for thermography were 1.09 (0.67, 1.52), 0.66 (0.32, 1.00), 0.86 (0.47, 1.26), and 0.45 (0.28, 0.62), respectively. p-Values were all <0.001. The differences in mean values (95% CI) for ultrasound scores, but not for TP, were statistically significant for (a) swollen tender joints (PD: 0.67 0.39, 0.96, p<0.001; GS: 0.86 0.54, 1.18, p<0.001) and (b) swollen non-tender joints (PD: 0.46 0.07, 0.84, p=0.021; GS: 0.83 0.37, 1.29, p<0.001) when compared to non-swollen non-tender joints.
Joints in RA patients have significantly higher temperature readings when ultrasound-detected joint inflammation is present. Swollen tender/non-tender joints exhibited a greater degree of ultrasound-detected joint inflammation than non-swollen non-tender joints, although their temperature readings were not significantly higher.
•Thermal imaging is safe, non-invasive with high feasibility for use.•RA joints have higher temperature readings in presence of ultrasound inflammation.•Further validation work in areas of potential clinical use is required.
The antituberculosis vaccine Bacillus Calmette–Guérin (BCG) induces nonspecific protection against heterologous infections, at least partly through induction of innate immune memory (trained ...immunity). The amplitude of the response to BCG is variable, but the factors that influence this response are poorly understood. Metabolites, either released by cells or absorbed from the gut, are known to influence immune responses, but whether they impact BCG responses is not known. We vaccinated 325 healthy individuals with BCG, and collected blood before, 2 weeks and 3 months after vaccination, to assess the influence of circulating metabolites on the immune responses induced by BCG. Circulating metabolite concentrations after BCG vaccination were found to have a more pronounced impact on trained immunity responses, such as the increase in IL-1β and TNF-α production upon
Staphylococcus aureus
stimulation, than on specific adaptive immune memory, assessed as IFN-γ production in response to
Mycobacterium tuberculosis
. Circulating metabolites at baseline were able to predict trained immunity responses at 3 months after vaccination and enrichment analysis based on the metabolites positively associated with trained immunity revealed enrichment of the tricarboxylic acid (TCA) cycle and glutamine metabolism, both of which were previously found to be important for trained immunity. Several new metabolic pathways that influence trained immunity were identified, among which taurine metabolism associated with BCG-induced trained immunity, a finding validated in functional experiments. In conclusion, circulating metabolites are important factors influencing BCG-induced trained immunity in humans. Modulation of metabolic pathways may be a novel strategy to improve vaccine and trained immunity responses.
Still's disease is a severe inflammatory syndrome characterized by fever, skin rash and arthritis affecting children and adults. Patients with Still's disease may also develop macrophage activation ...syndrome, a potentially fatal complication of immune dysregulation resulting in cytokine storm. Here we show that mTORC1 (mechanistic target of rapamycin complex 1) underpins the pathology of Still's disease and macrophage activation syndrome. Single-cell RNA sequencing in a murine model of Still's disease shows preferential activation of mTORC1 in monocytes; both mTOR inhibition and monocyte depletion attenuate disease severity. Transcriptomic data from patients with Still's disease suggest decreased expression of the mTORC1 inhibitors TSC1/TSC2 and an mTORC1 gene signature that strongly correlates with disease activity and treatment response. Unrestricted activation of mTORC1 by Tsc2 deletion in mice is sufficient to trigger a Still's disease-like syndrome, including both inflammatory arthritis and macrophage activation syndrome with hemophagocytosis, a cellular manifestation that is reproduced in human monocytes by CRISPR/Cas-mediated deletion of TSC2. Consistent with this observation, hemophagocytic histiocytes from patients with macrophage activation syndrome display prominent mTORC1 activity. Our study suggests a mechanistic link of mTORC1 to inflammation that connects the pathogenesis of Still's disease and macrophage activation syndrome.
Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders ...adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
Electronic inhomogeneity appears to be an inherent characteristic of the enigmatic cuprate superconductors. Here we report the observation of charge-density-wave correlations in the model cuprate ...superconductor HgBa2 CuO4+δ (Tc =72 K) via bulk Cu L3 -edge-resonant X-ray scattering. At the measured hole-doping level, both the short-range charge modulations and Fermi-liquid transport appear below the same temperature of about 200 K. Our result points to a unifying picture in which these two phenomena are preceded at the higher pseudogap temperature by q=0 magnetic order and the build-up of significant dynamic antiferromagnetic correlations. The magnitude of the charge modulation wave vector is consistent with the size of the electron pocket implied by quantum oscillation and Hall effect measurements for HgBa2 CuO4+δ and with corresponding results for YBa2 Cu3 O6+δ , which indicates that charge-density-wave correlations are universally responsible for the low-temperature quantum oscillation phenomenon.
•The dynamic response of the single walled and sandwich walled tubes subjected to an internal explosion was investigated.•An empirical formula was presented to predict the deformation or failure of a ...tube under the internal explosion.•An analytical model was proposed to describe the response of the sandwich tube under the internal blast loading.
Cylindrical metallic tubes are commonly used as a protective structure to contain explosives. This study focused on the response of single walled and sandwich walled cylindrical tubes subjected to an internal explosion. Firstly, real-life detonation experiments were performed to obtain the basic deformation patterns. Finite element (FE) simulations were then conducted in ANSYS and LS-DYNA to obtain the simulated data for deformation pattern. Those simulated results were then validated against the experimentally obtained data. Next, a parametric study was performed in order to obtain the main parameters in an explosive process while keeping the failure strain of the material constant. For single-walled tubes, these were namely found to be the mass of the PE4 explosive used (M), the thickness of the tube wall (h) and the stand-off distance (R). A non-dimensional empirical formula was obtained. Then the response of sandwich-walled tube filled with the closed-cell aluminum foam under PE4 charge was investigated numerically. The numerical results revealed that the deformation or failure, and the energy absorption of the sandwich tubes were significantly affected by the PE4 charge, and also the mass ratio of the tube to the foam. As a first step, a simplified one-dimensional axisymmetric analytical model was presented where the filled foam was assumed to have an initial rigid regime, followed by a perfectly-plastic stage and locking densification (R-PP-L). Comparison with the numerical model gives a fairly good agreement.
Mirror‐mode structures are widely observed in space plasma environments. Although plasma features within the structures have been extensively investigated in theoretical models and numerical ...simulations, relatively few observational studies have been made, due to a lack of high‐cadence measurements of particle distributions in previous space missions. In this work, electron dynamics associated with mirror‐mode structures are studied based on Magnetospheric Multiscale observations of electron pitch angle distributions. We define mirror‐mode peaks/troughs as the region where the magnetic field strength is greater/smaller than the mean field. The observations show that most electrons are trapped inside the mirror‐mode troughs and display a donut‐like pitch angle distribution configuration. Besides the trapped electrons in mirror‐mode troughs, we find that electrons are also trapped between ambient mirror‐mode peaks and coexisting untrapped electrons within the mirror‐mode structure. Analysis shows that the observed donut‐like electron distributions are the result of betatron cooling and the spatial dependence of electron pitch angles within the structure.
Key Points
Electron PADs of magnetosheath mirror modes are observed by MMS
The PADs display a characteristic donut‐like configuration
Betatron cooling and spatial dependence of electron pitch angle are able to produce such a distribution
Our ability to predict how temperature modifies phenology at the community scale is limited by our lack of understanding of responses by functional groups of flowering plants. These responses differ ...among species with different life histories. We performed a reciprocal transplant experiment along four elevation gradients (e.g., 3,200, 3,400, 3,600 and 3,800 m) to investigate the effects of warming (transferred downward) and cooling (transferred upward) on plant flowering functional groups (FFGs) and community phenological sequences (i.e., seven phenological events). Warming significantly decreased early-spring-flowering (ESF) plant coverage and increased mid-summer-flowering plant (MSF) coverage, while cooling had the opposite effect. All community phenological events were advanced by warming and delayed by cooling except for the date of complete leaf-coloring, which showed the opposite response. Warming and cooling could cause greater advance or delay in early-season phenological events of the community through increased coverage of MSF species, and warming could delay late-season phenological events of the community by increased coverage of ESF species. These results suggested that coverage change of FFGs in the community induced by temperature change could mediate the responses of the community phenological events to temperature change in the future. The response of phenological events to temperature change at the species level may not be sufficient to predict phenological responses at the community-level due to phenological compensation between species in the community.
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