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We explore the application of phase diversity to calibrate the non common path aberrations (NCPA) in the Gemini Planet Imager (GPI). This is first investigated in simulation in order to characterize the ideal technique parameters with simulated GPI calibration source data. The best working simulation parameters are derived and we establish the algorithm's capability to recover an injected astigmatism. Furthermore, the real data appear to exhibit signs of de-centering between the in and out of focus images that are required by phase diversity; this effect can arise when the diverse images are acquired in closed loop and are close to the non-linear regime of the wavefront sensor. We show in simulation that this effect can inhibit our algorithm, which does not take into account the impact of de-centering between images. To mitigate this effect, we validate the technique of using a single diverse image with our algorithm; this is first demonstrated in simulation and then applied to the real GPI data. Following this approach, we find that we can successfully recover a known astigmatism injection using the real GPI data and subsequently apply an NCPA correction to GPI (in the format of offset reference slopes) to improve the relative Strehl ratio by 5%; we note this NCPA correction application is rudimentary and a more thorough application will be investigated in the near future. Finally, the estimated NCPA in the form of astigmatism and coma agree well with the magnitude of the same modes reported by Poyneer et al. 2016.

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

What are the psychological consequences of the increasingly politicized nature of the COVID-19 pandemic in the United States relative to similar Western countries? In a two-wave study completed early (March) and later (December) in the pandemic, we found that polarization was greater in the United States ( N = 1,339) than in Canada ( N = 644) and the United Kingdom. ( N = 1,283). Political conservatism in the United States was strongly associated with engaging in weaker mitigation behaviors, lower COVID-19 risk perceptions, greater misperceptions, and stronger vaccination hesitancy. Although there was some evidence that cognitive sophistication was associated with increased polarization in the United States in December (but not March), cognitive sophistication was nonetheless consistently negatively correlated with misperceptions and vaccination hesitancy across time, countries, and party lines. Furthermore, COVID-19 skepticism in the United States was strongly correlated with distrust in liberal-leaning mainstream news outlets and trust in conservative-leaning news outlets, suggesting that polarization may be driven by differences in information environments.

The effect of blocky to lamellar phase transformation on the microstructure and micro-texture of a Magnesium-Rare earth alloy containing long-period stacking order (LPSO) phases were examined comprehensively at the isothermal temperature of 400 °C via multiaxial forging. A very fine-grained microstructure with an average grain size of 1 μm was achieved after applying three multi-axial forging (MAF) passes. Particle stimulated nucleation (PSN) along with continuous dynamic recrystallizations (CDRX) due to the blocky LPSO phases were realized to be the main reasons for the achievement of such fine microstructure. The deformation-induced blocky to lamellar phase transformation began at 1/3 pass and expanded through the whole microstructure after the third pass. Such phase transformation was found to be initiated by the fragmentation of blocky phases. As a result of PSN and CDRX mechanisms, two new rare earth (RE) texture components of and || Transverse Direction (TD) were formed at the second MAF pass that led to a highly randomized deformation texture. Nevertheless, the continuous breakdown of blocky phases and their subsequent phase transformation to lamellar LPSO suppressed PSN at the third deformation pass. Hence, the formed RE texture components were disappeared which in turn increased the texture intensity at this deformation pass.

Author(s): Lochmuller, Hanns; Behin, Anthony; Tournev, Ivailo; Tarnopolsky, Mark; Horvath, Rita; Pogoryelova, Oksana; Shah, Jinay; Koutsoukos, Tony; Skrinar, Alison; Kakkis, Emil; Bedrosian, Camille L; Mozaffar, Tahseen | Abstract: BackgroundGNE myopathy is a rare, autosomal recessive, muscle disease caused by mutations in GNE and is characterized by rimmed vacuoles on muscle biopsy and progressive distal to proximal muscle weakness.ObjectiveInvestigate the clinical presentation and progression of GNE myopathy.MethodsThe GNE Myopathy Disease Monitoring Program was an international, prospective, observational study in subjects with GNE myopathy. Muscle strength was assessed with hand-held dynamometry (HHD), with upper extremity (UE) and lower extremity (LE) composite scores reflecting upper and lower extremity muscle groups, respectively. The GNE myopathy-Functional Activity Scale (GNEM-FAS) was used to further assess impairment in mobility, upper extremity function, and self-care.ResultsEighty-seven of 101 enrolled subjects completed the trial until study closure by the sponsor; 60 completed 36 months. Mean (SD) HHD UE composite score decreased from 34.3 kg (32.0) at baseline to 29.4 kg (32.6) kg at month 36 (LS mean change [95%CI]: -3.8 kg [-5.9, -1.7]; P = 0.0005). Mean (SD) HHD LE composite score decreased from 32.0 kg (34.1) at baseline to 25.5 kg (31.2) at month 36 (LS mean change [95%CI]: -4.9 [-7.7, -2.2]; P = 0.0005). GNEM-FAS scores were more severe at baseline in subjects who walked l200 meters versus ≥200 meters in 6 minutes; in both groups, GNEM-FAS total, mobility, UE, and self-care scores decreased from baseline through month 36.ConclusionsThese findings demonstrate progressive decline in muscle strength in GNE myopathy and provide insight into the appropriate tools to detect clinically meaningful changes in future GNE myopathy interventional trials.

Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus. The parasitic marine dinoflagellate Amoebophrya is the first known eukaryote with aerobic mitochondria without a genome.

Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg–1·d–1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg–1·d–1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease. Supplemental Digital Content is available in the text.

AbstractAstrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).