Combustion Synthesis of Large Bulk Nanostructured Ni 65

A large bulk nanostructured Ni65Al21Cr14 alloy with dimensions of Φ 100 mm × 6 mm was produced by combustion synthesis technique followed with rapid solidification. The Ni65Al21Cr14 alloy was composed of γ′-Ni3Al/γ-Ni(Al, Cr) eutectic matrix and γ-Ni(Al, Cr) dendrite. The eutectic matrix consisted of 80–150 nm cuboidal γ′-Ni3Al and 2–5 nm γ-Ni(Al, Cr) boundary. The dentrite was comprised of high-density growth twins with about 3–20 nm in width. The nanostructured Ni65Al21Cr14 alloy exhibited simultaneously high fracture strength of 2200 MPa and good ductility of 26% in compression test

Crystal structure of E. coli arginyl-tRNA synthetase and ligand binding studies revealed key residues in arginine recognition

The arginyl-tRNA synthetase (ArgRS) catalyzes the esterification reaction between L-arginine and its cognate tRNA(Arg). Previously reported structures of ArgRS shed considerable light on the tRNA recognition mechanism, while the aspect of amino acid binding in ArgRS remains largely unexplored. Here we report the first crystal structure of E. coli ArgRS (eArgRS) complexed with L-arginine, and a series of mutational studies using isothermal titration calorimetry (ITC). Combined with previously reported work on ArgRS, our results elucidated the structural and functional roles of a series of important residues in the active site, which furthered our understanding of this unique enzyme. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-013-0012-1) contains supplementary material, which is available to authorized users

Mixed Total Variation and L

Optical tomography is an emerging and important molecular imaging modality. The aim of optical tomography is to reconstruct optical properties of human tissues. In this paper, we focus on reconstructing the absorption coefficient based on the radiative transfer equation (RTE). It is an ill-posed parameter identification problem. Regularization methods have been broadly applied to reconstruct the optical coefficients, such as the total variation (TV) regularization and the L1 regularization. In order to better reconstruct the piecewise constant and sparse coefficient distributions, TV and L1 norms are combined as the regularization. The forward problem is discretized with the discontinuous Galerkin method on the spatial space and the finite element method on the angular space. The minimization problem is solved by a Jacobian-based Levenberg-Marquardt type method which is equipped with a split Bregman algorithms for the L1 regularization. We use the adjoint method to compute the Jacobian matrix which dramatically improves the computation efficiency. By comparing with the other imaging reconstruction methods based on TV and L1 regularizations, the simulation results show the validity and efficiency of the proposed method

Cardiovascular Autonomic Neuropathy Is an Independent Risk Factor for Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes

Aim. This study aimed to evaluate the association between cardiovascular autonomic neuropathy (CAN) and left ventricular diastolic dysfunction (LVDD) in type 2 diabetes patients. Methods. 315 type 2 diabetes patients from inpatients of Drum Tower Hospital were included and classified into no CAN (NCAN), possible CAN (PCAN), and definite CAN (DCAN) based on cardiovascular autonomic reflex tests. The left ventricular diastolic function was assessed by tissue Doppler imaging echocardiography. Results. The distribution of NCAN, PCAN, and DCAN was 11.4%, 51.1%, and 37.5%, respectively. The proportion of LVDD increased among the groups of NCAN, PCAN, and DCAN (39.4%, 45.3%, and 68.0%, = 0.001). Patients with DCAN had higher filling pressure ( / ratio) (10.9 ± 2.7 versus 9.4 ± 2.8, = 0.013) and impaired diastolic performance ( ) (6.8 ± 1.7 versus 8.6±2.4, = 0.004) compared with NCAN. CAN was found to be an independent risk factor for LVDD from the multivariate regression analysis (OR = 1.628, = 0.009, 95% CI 1.131-2.344). Conclusions. Our results indicated that CAN was an independent risk marker for the presence of LVDD in patients with diabetes. Early diagnosis and treatment of CAN are advocated for preventing LVDD in type 2 diabetes

Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression

GARS- related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment

The majority of patients with spinal muscular atrophy (SMA) identified to date harbor a biallelic exonic deletion of SMN1. However, there have been reports of SMA- like disorders that are independent of SMN1, including those due to pathogenic variants in the glycyl- tRNA synthetase gene (GARS1). We report three unrelated patients with de novo variants in GARS1 that are associated with infantile- onset SMA (iSMA). Patients were ascertained during inpatient hospital evaluations for complications of neuropathy. Evaluations were completed as indicated for clinical care and management and informed consent for publication was obtained. One newly identified, disease- associated GARS1 variant, identified in two out of three patients, was analyzed by functional studies in yeast complementation assays. Genomic analyses by exome and/or gene panel and SMN1 copy number analysis of three patients identified two previously undescribed de novo missense variants in GARS1 and excluded SMN1 as the causative gene. Functional studies in yeast revealed that one of the de novo GARS1 variants results in a loss- of- function effect, consistent with other pathogenic GARS1 alleles. In sum, the patients’ clinical presentation, assessments of previously identified GARS1 variants and functional assays in yeast suggest that the GARS1 variants described here cause iSMA. GARS1 variants have been previously associated with Charcot- Marie- Tooth disease (CMT2D) and distal SMA type V (dSMAV). Our findings expand the allelic heterogeneity of GARS- associated disease and support that severe early- onset SMA can be caused by variants in this gene. Distinguishing the SMA phenotype caused by SMN1 variants from that due to pathogenic variants in other genes such as GARS1 significantly alters approaches to treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154914/1/ajmga61544_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154914/2/ajmga61544.pd

Understanding how excess lead iodide precursor improves halide perovskite solar cell performance

The presence of excess lead iodide in halide perovskites has been key for surpassing 20% photon-to-power conversion efficiency. To achieve even higher power conversion efficiencies, it is important to understand the role of remnant lead iodide in these perovskites. To that end, we explored the mechanism facilitating this effect by identifying the impact of excess lead iodide within the perovskite film on charge diffusion length, using electron-beam-induced current measurements, and on film formation properties, from grazing-incidence wide-angle X-ray scattering and high-resolution transmission electron microscopy. Based on our results, we propose that excess lead iodide in the perovskite precursors can reduce the halide vacancy concentration and lead to formation of azimuthal angle-oriented cubic alpha-perovskite crystals in-between 0 degrees and 90 degrees. We further identify a higher perovskite carrier concentration inside the nanostructured titanium dioxide layer than in the capping layer. These effects are consistent with enhanced lead iodide-rich perovskite solar cell performance and illustrate the role of lead iodide