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Intramuscular fat deposition represents a negative prognostic factor for several myopathies, metabolic diseases and aging. Fibro-adipogenic progenitors (FAPs) are considered as the main source of intramuscular adipocytes, but the mechanisms controlling their adipogenic potential are still not elucidated in humans. The aim of this study was to explore the regulation of human FAP adipogenesis by macrophages. We found that CD140a-expressing FAPs were located close to CD68 positive macrophages in muscles from patients with Duchenne muscular dystrophy (DMD). This strongly suggests a potential interaction between FAPs and macrophages in vivo . Isolated human primary FAPs were then differentiated in the presence of conditioned media obtained from primary blood monocyte-polarized macrophages. Molecules released by IL-1β-polarized macrophages (M(IL-1β)) drastically reduced FAP adipogenic potential as assessed by decreased cellular lipid accumulation and reduced gene expression of adipogenic markers. This was associated with an increased gene expression of pro-inflammatory cytokines in FAPs. Conversely, factors secreted by IL-4-polarized macrophages (M(IL-4)) enhanced FAP adipogenesis. Finally, the inhibition of FAP adipocyte differentiation by M(IL-1β) macrophages requires the stimulation of Smad2 phosphorylation of FAPs. Our findings identify a novel potential crosstalk between FAPs and M(IL-1β) and M(IL-4) macrophages in the development of adipocyte accumulation in human skeletal muscles.

Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy. Immunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids. The per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21-128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22-132) (Thymo-group) (p = 0.69). We found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.

Flow generation by colloidal motors activated by external stimuli is an important issue for active matter physics and several nanotechnological or biomedical applications. For instance, flow recirculation generated by rotating magnetic self-assemblies allows effective ‘pumping’ of a thrombolytic drug towards a blood clot along a blocked vessel. However, the physics of the flow generation in this case remains still poorly explored. This study is focused on the generation of a recirculation flow of a magnetic colloid (aqueous suspension of iron oxide nanoparticles with partially screened electrostatic repulsion) within a closed microfluidic channel via application of an external rotating magnetic field. The colloid undergoes reversible phase separation manifested through the appearance of micron-sized elongated aggregates. They synchronously rotate with the magnetic field and can generate macroscopic flows only in the presence of gradients of the aggregate concentration across the channel induced by superposition of a weak magnetic field gradient to the homogeneous rotating field. We achieve recirculation flows with a characteristic speed ${\\sim} 5{-}8\\;{\\rm \\mu}\\textrm{m}\\;{\\textrm{s}^{ - \\textrm{1}}}$ at low magnetic field amplitude and frequency (${H_0} \\approx 3{-}10\\;\\textrm{kA}\\;{\\textrm{m}^{ - 1}}$, ${f = 5{-}15\\ \\textrm{Hz}}$) at low nanoparticle volume fraction ${\\varphi _p} = (1.6{-}3.2) \\times {10^{ - 3}}$. The concentration and velocity profiles have been assessed experimentally through particle tracking and particle image velocimetry, and have also been computed using the hydrodynamic diffusion approach coupled with the momentum balance equation with a magnetic torque term. The model correctly reproduces the shape of the experimental concentration and velocity fields and explains complex behaviours of the average recirculation speed as a function of governing parameters (${H_0}$, f, ${\\varphi _p}$, channel size).

The effect of reflection is studied experimentally and theoretically on a high-power 110-GHz gyrotron operating in the TE 22,6 mode in 3μs pulses at 96kV, 40A. The experimental setup allows variation of the reflected power from 0 to 33% over a range of gyrotron operating conditions. The phase of the reflection is varied by translating the reflector along the axis. Operating at a higher efficiency point, at 4.40T with 940kW of output power, reflected power exceeding 11% causes a switch from operation in the TE 22,6 to simultaneous operation in the TE 22,6 and TE 21,6 modes with a large decrease of the total gyrotron output power. This switching effect is in good agreement with simulations using the MAGY code. Operating at a more stable point, 4.44T with 580kW of output power, when the reflection is increased, the output power remains in the TE 22,6 mode but it decreases monotonically with increasing reflection, dropping to 200kW at 33% reflection. Furthermore, at a reflection above 22%, a power modulation at 25 to 30MHz is observed, independent of the phase of the reflected wave. Such a modulated signal may be useful in spectroscopic and other applications.

A Correction to this paper has been published: https://doi.org/10.1007/s10762-021-00783-w

Simple analytical formulae are presented for the design of linear tapers with very low mode conversion loss in overmoded corrugated waveguides. For tapers from waveguide radius a 2 to a 1 , with a 1 < a 2 , the optimal length of the taper is 3.198 a 1 a 2 / λ . Here, λ is the wavelength of radiation. The fractional loss of the HE 11 mode in an optimized taper is 0.0293 ( a 2 − a 1 ) 4 / a 1 2 a 2 2 . These formulae are accurate when a 2 ≲2 a 1 . Slightly more complex formulae, accurate for a 2 ≤4 a 1 , are also presented in this paper. The loss in an overmoded corrugated linear taper is less than 1 % when a 2 ≤2.12 a 1 and less than 0.1 % when a 2 ≤1.53 a 1 . The present analytic results have been benchmarked against a rigorous mode matching code and have been found to be very accurate. The results for linear tapers are compared with the analogous expressions for parabolic tapers. Parabolic tapers may provide lower loss, but linear tapers with moderate values of a 2 / a 1 may be attractive because of their simplicity of fabrication.

Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients' access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations. To address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus). A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55-3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05-6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection. In this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification. National Clinical Trial protocol ID: NCT03438058.

The present study examined the effect of early life stress (ELS) on the glucocorticoid receptor gene (NR3C1) methylation, the associations between NR3C1 methylation and behavior problems, and the effect of the program Parents as Teachers (PAT) on NR3C1 methylation. Participants included 132 children, 72 assigned to the PAT intervention group and 60 to the PAT control group. Children were aged 3 years, and were living in psychosocially at-risk families. We assessed NR3C1 methylation of the NGFI-A binding regions of exon 1F via sodium bisulfite sequencing from saliva DNA. Results indicated that (a) children living in families receiving PAT had decreased methylation at one single cytosine–guanine dinucleotides (CpG) site; (b) current maternal depressive symptoms and parental disagreement were predictive of increased methylation of mean NGFI-A and three single CpG sites; and (c) increased methylation of mean NGFI-A and one single CpG site was significantly associated with increased internalizing and externalizing symptoms. In addition, mean NGFI-A was a mediator of the association between parental disagreement and a child's affective problems. These results suggest that PAT may contribute to preventing NR3C1 methylation in preschool children living in psychosocially at-risk situations, and confirm previous findings on the associations between ELS, NR3C1 methylation, and behavior problems.

Caliciviruses are disseminated by the fecal-oral route and are found in contaminated surface and ground waters. The US Environmental Protection Agency (EPA) is interested in preventing calicivirus contamination in treated waters used for consumption, and these viruses are on the EPA's “contaminant candidate list” for regulatory consideration in drinking waters. These viruses also present a health threat for recreation and shellfish-growing waters. However, before EPA can make regulatory decisions regarding caliciviruses, significant information and technology needs must be established, including analytical methods for sampling, identifying, and quantifying the viruses; applicability of surrogates to determine their presence; efficacy of water and wastewater treatment or disinfection; waterborne occurrence levels and distribution; dose response; and the viruses' effect(s) on health. Future drinking-water regulations may need to ensure that treatments are adequate to remove caliciviruses from source waters. For recreation and shellfish-growing waters, surrogate indicators and health criteria may need to be based upon establishing risks of exposure to caliciviruses.

The activation of bipolar conduction was investigated for two 4H-SiC 10 kV JBS-diodes which differ in the area ratio between p-doped and n-doped regions (Ws/WPin). Quasi-static measurements at low electric current densities (j < 2.5 Acm-2) were performed in a temperature range between 25°C and 500°C. The lower ratio (Ws/WPin) leads to a higher threshold voltage. On the other hand lower electric power density is neccessary to trigger temperature enhanced bipolar activation. Moreover, the lower ratio improves the leakage currents in blocking direction. Dynamic surge current investigations were performed in a temperature range between 25°C and 250°C. The turning voltages, which indicate the transition from unipolar to bipolar conduction, are lower for the diode with smaller ratio (Ws/WPin) but the self-heating of the device is more severe in comparison to the other diode with the larger ratio. Both devices are stable under extreme conditions (high temperatures/ surge current) and exhibit special benefits for different applications.