To develop a model-guided self-supervised deep learning MRI reconstruction framework called reference-free latent map extraction (RELAX) for rapid quantitative MR parameter mapping. Two physical models are incorporated for network training in RELAX, including the inherent MR imaging model and a quantitative model that is used to fit parameters in quantitative MRI. By enforcing these physical model constraints, RELAX eliminates the need for full sampled reference data sets that are required in standard supervised learning. PF-8380 inhibitor Meanwhile, RELAX also enables direct reconstruction of corresponding MR parameter maps from undersampled k-space. Generic sparsity constraints used in conventional iterative reconstruction, such as the total variation constraint, can be additionally included in the RELAX framework to improve reconstruction quality. The performance of RELAX was tested for accelerated T and T mapping in both simulated and actually acquired MRI data sets and was compared with supervised learning and cono be further extended to other quantitative MRI applications by incorporating corresponding quantitative imaging models.Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hematologic disease characterized by chronic complement-mediated hemolysis and thrombosis. Despite treatment with eculizumab, a C5 inhibitor, 72% of individuals remain anemic. Pegcetacoplan (APL-2), a PEGylated C3 inhibitor, has the potential to provide more complete hemolysis control in patients with PNH. This open-label, phase Ib study was designed to assess the safety, tolerability, and pharmacokinetics of pegcetacoplan in subjects with PNH who remained anemic during treatment with eculizumab. Pharmacodynamic endpoints were also assessed as an exploratory objective of this study. Data are presented for six subjects in cohort 4 who received treatment for up to 2 years. In total, 427 treatment-emergent adverse events (TEAEs) were reported, 68 of which were possibly related to the study drug. Eight serious TEAEs occurred in two subjects; three of these events were considered possibly related to the study drug. Pegcetacoplan pharmacokinetic concentrations accumulated with repeated dosing, and steady state was reached at approximately 6-8 weeks. Lactate dehydrogenase levels were well controlled by eculizumab at baseline. Pegcetacoplan increased hemoglobin levels and decreased both reticulocyte count and total bilirubin in all six subjects. Improvements were observed in Functional Assessment of Chronic Illness Therapy Fatigue scores. Two subjects discontinued for reasons unrelated to pegcetacoplan. All four subjects who completed the study transitioned to pegcetacoplan monotherapy following eculizumab discontinuation and avoided transfusions. In this small study, pegcetacoplan therapy was generally well-tolerated, and resulted in an improved hematological response by achieving broad hemolysis control, enabling eculizumab discontinuation.The objective of this study was to find the role of LncRNA SNHG12 in the regulation of hypertensive vascular endothelial injury. LncRNA SNHG12 and miR-25-3p expression were detected by quantitative RT-PCR. Protein levels of Sirtuin 6 (SIRT6), endothelial cell (EC) senescence markers p16 and p21, and EC marker CD31 were measured by Western blot. The apoptosis of HUVECs was detected by flow cytometry. The binding between LncRNA SNHG12 and miR-25-3p was verified by dual luciferase reporter gene assay and RNA pull-down assay. As a result, LncRNA SNHG12 was down-regulated in aortic primary ECs isolated from Ang II-induced hypertensive mice and 1 kidney/deoxycorticosterone acetate/salt-induced hypertensive mice. In Ang II-treated HUVECs, the expression level of SNHG12 was reduced and the overexpression of SNHG12 inhibited EC senescence markers p16 and p21 expressions, the apoptosis of HUVECs, and caspase-3 activity. Further investigation confirmed that LncRNA SNHG12 bound to miR-25-3p, and negatively regulated miR-25-3p expression. MiR-25-3p directly targeted SIRT6 and negatively regulated SIRT6 expression. In addition, SNHG12 overexpression inhibited Ang II-induced HUVECs injury through regulating miR-25-3p. Finally, in vivo experiments showed LncRNA SNHG12 overexpression alleviated vascular endothelial injury in Ang II-induced hypertensive mice. In conclusion, LncRNA SNHG12 alleviates vascular endothelial injury induced by hypertension through miR-25-3p/SIRT6 pathway. In this work, we investigated how the position of the radiofrequency (RF) shield can affect the signal-to-noise ratio (SNR) of a receive RF coil. Our aim was to obtain physical insight for the design of a 10.5T 32-channel head coil, subject to the constraints on the diameter of the RF shield imposed by the head gradient coil geometry. We used full-wave numerical simulations to investigate how the SNR of an RF receive coil depends on the diameter of the RF shield at ultra-high magnetic field (UHF) strengths (≥7T). Our simulations showed that there is an SNR-optimal RF shield size at UHF strength, whereas at low field the SNR monotonically increases with the shield diameter. For a 32-channel head coil at 10.5T, an optimally sized RF shield could act as a cylindrical waveguide and increase the SNR in the brain by 27% compared to moving the shield as far as possible from the coil. Our results also showed that a separate transmit array between the RF shield and the receive array could considerably reduce SNR even if they are decoupled. At sufficiently high magnetic field strength, the design of local RF coils should be optimized together with the design of the RF shield to benefit from both near field and resonant modes.At sufficiently high magnetic field strength, the design of local RF coils should be optimized together with the design of the RF shield to benefit from both near field and resonant modes.Silver is a non-essential metal used in medical applications as an antimicrobial agent, but it is also toxic for biological systems. To investigate the molecular basis of silver resistance in yeast, we employed evolutionary engineering using successive batch cultures at gradually increased silver stress levels up to 0.25-mM AgNO3 in 29 populations and obtained highly silver-resistant and genetically stable Saccharomyces cerevisiae strains. Cross-resistance analysis results indicated that the silver-resistant mutants also gained resistance against copper and oxidative stress. Growth physiological analysis results revealed that the highly silver-resistant evolved strain 2E was not significantly inhibited by silver stress, unlike the reference strain. Genomic and transcriptomic analysis results revealed that there were mutations and/or significant changes in the expression levels of the genes involved in cell wall integrity, cellular respiration, oxidative metabolism, copper homeostasis, endocytosis and vesicular transport activities.