Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous ...loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.
Asymmetric yield behavior in tension and compression is a common and usually undesirable feature of wrought magnesium alloys. To prevent yield asymmetry, it is necessary to favor slip over twinning, ...as it is the unidirectional nature of twinning combined with the strong textures produced in wrought magnesium alloys that produce yield asymmetry. In this article, the potential to use precipitates to strengthen selectively against twin growth is discussed. The effect of precipitate's shape and habit on strengthening of slip and twinning is calculated using simple Orowan-based models. It is shown that basal plate precipitates, although being poor strengtheners against basal slip, are good strengtheners against twin growth. This is because they produce the maximum unrelaxed back-stress when they remain unsheared inside the twin. The predictions of the model have been validated against experiments for two alloys that form different precipitate types: AZ91 (basal plates). and Z5 (c-axis rods). Crystal plasticity modeling has been used to predict that an optimized distribution of basal plate precipitates is expected to strongly reduce yield asymmetry, even in strongly textured magnesium alloy.
The response of the metal-to-ligand charge-transfer (MLCT) band to variability in terminal substituents within a related set of tridentate polypyridyl and cyclometalated Ru(II) complexes is reported. ...These complexes are formulated as Ru(tpy-R1)(tpy-R2)(PF6)2 (1−6; tpy = 2,2′:6′,2′′-terpyridine; R1 = −H, −2-furyl, or −OMe; R2 = −H, −2-furyl, or −CO2H) and Ru(tpy-R2)(dpb-R1)PF6 (7−10; Hdpb = 1,3-di(pyridin-2-yl)benzene; R2 = −H or −2-furyl; R1 = −H or −OMe). Absorption spectra for the Ru(tpy-R1)(tpy-R2)2+ series highlight the sensitivity of the MLCT band to the indicated substituents at the 4′ position of one or both tpy ligands (e.g., a bathochromic shift up to 24 nm coupled with a 2-fold increase in absorption intensity). Similar observations are made for the Ru(tpy-R2)(dpb-R1)+ series, where a single Ru−N dative bond is replaced by a Ru−C σ-bond to form a cyclometalated complex. The reduced symmetry at the metal center within this series results in a broadening of the lowest-energy MLCT band, while an additional set of transitions at higher energies emerges that involves an excited state localized on the cyclometalating ligand. These MLCT transitions collectively render a broad absorption envelope of substantial intensity at wavelengths longer than ca. 525 nm. Optimal results are obtained for compound 10 (R1 = −OMe; R2 = −2-furyl), where a strong electron-donating group is situated para to the Ru−C bond (λmax = 523 nm; ε = 2.6 × 104 M−1 cm−1). This approach imparts substantial polarization within the molecule, which should benefit excited-state electron-transfer reactions for photosensitizing applications (e.g., dye-sensitized solar cells). Spectroscopic data are corroborated by electrochemical and TD-DFT measurements for all compounds.
Purpose
To characterize the effect of fat on modified Look–Locker inversion recovery (MOLLI) T1 maps of the liver. The balanced steady‐state free precession (bSSFP) sequence causes water and fat ...signals to have opposite phase when repetition time (TR) = 2.3 msec at 3T. In voxels that contain both fat and water, the MOLLI T1 measurement is influenced by the choice of TR.
Materials and Methods
MOLLI T1 measurements of the liver were simulated using the Bloch equations while varying the hepatic lipid content (HLC). Phantom scans were performed on margarine phantoms, using both MOLLI and spin echo inversion recovery sequences. MOLLI T1 at 3T and HLC were determined in patients (n = 8) before and after bariatric surgery.
Results
At 3T, with HLC in the 0–35% range, higher fat fraction values lead to longer MOLLI T1 values when TR = 2.3 msec. Patients were found to have higher MOLLI T1 at elevated HLC (T1 = 929 ± 97 msec) than at low HLC (T1 = 870 ± 44 msec).
Conclusion
At 3T, MOLLI T1 values are affected by HLC, substantially changing MOLLI T1 in a clinically relevant range of fat content. J. Magn. Reson. Imaging 2016;44:105–111.
Characterization of the redox properties of TiO2 interfaces sensitized to visible light by a series of cyclometalated ruthenium polypyridyl compounds containing both a terpyridyl ligand with three ...carboxylic acid/carboxylate or methyl ester groups for surface binding and a tridentate cyclometalated ligand with a conjugated triarylamine (NAr3) donor group is described. Spectroelectrochemical studies revealed non-Nernstian behavior with nonideality factors of 1.37 ± 0.08 for the RuIII/II couple and 1.15 ± 0.09 for the NAr3 •+/0 couple. Pulsed light excitation of the sensitized thin films resulted in rapid excited-state injection (k inj > 108 s–1) and in some cases hole transfer to NAr3 TiO2(e–)/RuIII–NAr3 → TiO2(e–)/RuII–NAr3 •+. The rate constants for charge recombination TiO2(e–)/RuIII–NAr3 → TiO2/RuII–NAr3 or TiO2(e–)/RuII–NAr3 •+ → TiO2/RuII–NAr3 were insensitive to the identity of the cyclometalated compound, while the open-circuit photovoltage was significantly larger for the compound with the highest quantum yield for hole transfer, behavior attributed to a larger dipole moment change (Δμ = 7.7 D). Visible-light excitation under conditions where the RuIII centers were oxidized resulted in injection into TiO2 TiO2/RuIII–NAr3 + hν → TiO2(e–)/RuIII–NAr3 •+ followed by rapid back interfacial electron transfer to another oxidized compound that had not undergone excited-state injection TiO2(e–)/RuIII–NAr3 → TiO2/RuII–NAr3. The net effect was the photogeneration of equal numbers of fully reduced and fully oxidized compounds. Lateral intermolecular hole hopping (TiO2/RuII–NAr3 + TiO2/RuIII–NAr3 •+ → 2TiO2/RuIII–NAr3) was observed spectroscopically and was modeled by Monte Carlo simulations that revealed an effective hole hopping rate of (130 ns)−1.
Abstract Background Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular ...disease progression. Objectives The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. Methods Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. Results There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was –3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio GMR: 0.568; 95% confidence interval CI: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (–4.30 mg/dl range: –8.5 to –0.55 mg/dl; p = 0.025 at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. Conclusions There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930 )
Accurate assessment of plaque accumulation near the carotid bifurcation is important for the effective prevention and treatment of stroke. However, vessel and plaque delineation using MRI can be ...limited by low contrast-to-noise ratio (CNR) and long acquisition times. In this work, a 10-channel phased-array receive coil design for bilateral imaging of the carotid bifurcation using 3T MRI is proposed.
The proposed 10-channel receive coil was compared to a commercial 4-channel receive coil configuration using data acquired from phantoms and healthy volunteers (N = 9). The relative performance of the coils was assessed, by comparing signal-to-noise ratio (SNR), noise correlation, g-factor noise amplification, and the CNR between vessel wall and lumen using black-blood sequences. Patient data were acquired from 12 atherosclerotic carotid artery disease patients.
The 10-channel coil consistently provided substantially increased SNR in phantoms (+77 ± 27%) and improved CNR in healthy carotid arteries (+62 ± 11%), or reduced g-factor noise amplification. Patient data showed excellent delineation of atherosclerotic plaque along the length of the carotid bifurcation using the 10-channel coil.
The proposed 10-channel coil design allows for improved visualization of the carotid arteries and the carotid bifurcation and increased parallel imaging acceleration factors relative to a commercial 4-channel coil design.
The plastic deformation of single crystal magnesium is strongly anisotropic. This gives rise to deformation incompatibilities between grains during polycrystalline deformation, which are thought to ...limit ductility and formability. Wrought polycrystalline magnesium alloys are far from brittle, especially in uniaxial tension, implying that these incompatibilities can be accommodated to some extent, although it is not clear how. We have used high-resolution digital image correlation (HRDIC), supported by electron backscatter diffraction (EBSD), to study quantitatively and at the microstructural scale the accommodation of deformation incompatibility in an AZ31 magnesium alloy. Using a new gold remodelling procedure that improves the spatial resolution to 44 nm, we quantified the deformation heterogeneity after a small stretch in uniaxial tension. Our results confirm that polycrystalline deformation is very heterogeneous, with local axial true strains at grain boundaries 32 times higher than the applied average strain of 0.027, and 18 times higher at slip bands within grains. The local and macroscopic deformation gradients are very different in character as well as magnitude. The resultant deformation incompatibility is accommodated primarily by gradients in basal slip and the activation of difficult slip in “hard” grains, giving rise to grain breakup, with a smaller contribution by enhanced grain boundary shear and twinning. These results support the idea that a homogeneous distribution of “hard” and “soft” grains can prevent the development of strain localization and, therefore, that controlling texture and microtexture is a powerful way of enhancing the formability of magnesium alloys without reducing their single crystal plastic anisotropy.
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