The synthesis and properties of the hybrid organic/inorganic germanium perovskite compounds, AGeI3, are reported (A = Cs, organic cation). The systematic study of this reaction system led to the ...isolation of 6 new hybrid semiconductors. Using CsGeI3 (1) as the prototype compound, we have prepared methylammonium, CH3NH3GeI3 (2), formamidinium, HC(NH2)2GeI3 (3), acetamidinium, CH3C(NH2)2GeI3 (4), guanidinium, C(NH2)3GeI3 (5), trimethylammonium, (CH3)3NHGeI3 (6), and isopropylammonium, (CH3)2C(H)NH3GeI3 (7) analogues. The crystal structures of the compounds are classified based on their dimensionality with 1–4 forming 3D perovskite frameworks and 5–7 1D infinite chains. Compounds 1–7, with the exception of compounds 5 (centrosymmetric) and 7 (nonpolar acentric), crystallize in polar space groups. The 3D compounds have direct band gaps of 1.6 eV (1), 1.9 eV (2), 2.2 eV (3), and 2.5 eV (4), while the 1D compounds have indirect band gaps of 2.7 eV (5), 2.5 eV (6), and 2.8 eV (7). Herein, we report on the second harmonic generation (SHG) properties of the compounds, which display remarkably strong, type I phase-matchable SHG response with high laser-induced damage thresholds (up to ∼3 GW/cm2). The second-order nonlinear susceptibility, χS (2), was determined to be 125.3 ± 10.5 pm/V (1), (161.0 ± 14.5) pm/V (2), 143.0 ± 13.5 pm/V (3), and 57.2 ± 5.5 pm/V (4). First-principles density functional theory electronic structure calculations indicate that the large SHG response is attributed to the high density of states in the valence band due to sp-hybridization of the Ge and I orbitals, a consequence of the lone pair activation.
An in silico study of Aspergillus flavus genome stability uncovered significant variations in both coding and non-coding regions. The non-coding insertions uniformly consisted of AT-rich sequences ...that are evolutionarily maintained, albeit distributed at widely different sites in an array of A. flavus strains. A survey of ≥ 2kb AT-rich elements (AT ≥ 70%; ATEs) in non-centromeric regions uncovered two major categories of ATEs. The first category is composed of homologous insertions at ectopic, non-allelic sites that contain homology to transposable elements (TEs; Classes B, C, D, and E). Strains differed significantly in frequency, position, and TE type, but displayed a common enrichment in subtelomeric regions. The TEs were heavily mutated, with patterns consistent with the ancestral activity of repeat-induced point mutations (RIP). The second category consists of a conserved set of novel subtelomeric ATE repeats (Classes A, G, G, H, I and J) which lack discernible TEs and, unlike TEs, display a constant polarity relative to the telomere. Members of one of these classes are derivatives of a progenitor ATE that is predicted to have undergone extensive homologous recombination during evolution. A third category of ATEs consists of ~100 kb regions at each centromere. Centromeric ATEs and TE clusters within these centromeres display a high level of sequence identity between strains. These studies suggest that transposition and RIP are forces in the evolution of subtelomeric and centromeric structure and function.
We describe two methods of automated covalent docking using Autodock4: the two‐point attractor method and the flexible side chain method. Both methods were applied to a training set of 20 diverse ...protein–ligand covalent complexes, evaluating their reliability in predicting the crystallographic pose of the ligands. The flexible side chain method performed best, recovering the pose in 75% of cases, with failures for the largest inhibitors tested. Both methods are freely available at the AutoDock website (http://autodock.scripps.edu).
Two types of pure cellulose, Avicel PH-101 and Whatman filter paper, were treated with an acid-chlorite delignification procedure in the presence of varying amounts of incorporated lignin, and the ...molecular weight distributions and degrees of polymerization (DP) of derivatized cellulose were determined by gel permeation chromatography (GPC). Avicel samples with 0% added lignin showed a DP reduction of nearly 5% during acid-chlorite delignification, compared to a 1% drop in DP with 30% added lignin. Lignin-free filter paper samples showed a DP reduction of nearly 35% after hollocellulose delignification. This drop in DP was reduced to less than 12% for samples which contained 30% lignin. Thus, the presence of lignin in biomass samples minimized the DP reduction of cellulose due to acid catalyzed cleavage during acid-chlorite delignification.
The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer–related deaths, but treatment is usually curative following early ...detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.
The pyrolysis of softwood (SW) kraft lignin was examined at 400, 500, 600, and 700 °C. The yields of pyrolysis oil, char, and gas were determined to be 35−44%, 57−38% and 8−18%, respectively. The ...pyrolysis oil has a comparable heating value with ethanol and coal. The elevated temperature of 700 °C was found as the point of primary decomposition of lignin and the secondary decomposition of pyrolysis oil. Gel permeation chromatography (GPC) and quantitative 13C and 31P NMR were used to characterize the pyrolysis oil. A 13C NMR database was created to provide a more accurate chemical shift assignment database for analysis of pyrolysis oils. On the basis of the results of 13C and 31P NMR for the pyrolysis oil, aliphatic hydroxyl, carboxyl, and methoxyl groups are eliminated during pyrolysis. Cleavage of ether bonds in lignin was also shown to be a primary decomposition reaction occurring during thermal treatment. The results of GPC analysis indicated that lower pyrolysis temperatures yielded a bio-oil that had a lower molecular weight and lower polydispersity value.
In modeling ligand–protein interactions, the representation and role of water are of great importance. We introduce a force field and hydration docking method that enables the automated prediction of ...waters mediating the binding of ligands with target proteins. The method presumes no prior knowledge of the apo or holo protein hydration state and is potentially useful in the process of structure-based drug discovery. The hydration force field accounts for the entropic and enthalpic contributions of discrete waters to ligand binding, improving energy estimation accuracy and docking performance. The force field has been calibrated and validated on a total of 417 complexes (197 training set; 220 test set), then tested in cross-docking experiments, for a total of 1649 ligand–protein complexes evaluated. The method is computationally efficient and was used to model up to 35 waters during docking. The method was implemented and tested using unaltered AutoDock4 with new force field tables.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease (CLD) in North America. It is a growing contributor to the burden of CDL requiring liver transplantation. ...Cirrhosis is also associated with an increased risk of hepatocellular cancer, which may occur even in the absence of cirrhosis in subjects with nonalcoholic steatohepatitis (NASH), the histological form of NAFLD associated with increased liver‐related mortality. The diagnosis of NASH currently requires a liver biopsy. There are also no U.S. Food and Drug Administration (FDA)‐approved therapies for NASH. Therefore, there is a need to develop better diagnostic and therapeutic strategies for patients with NASH, targeting both those with early‐stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. The long relatively asymptomatic time interval in the progression of NAFLD and NASH to cirrhosis and ultimately liver failure, along with gaps in knowledge regarding disease modifiers, combine to present significant challenges in trial design. Therefore, there is an urgent need to develop methods to identify the populations at particular risk of disease progression and validate endpoints that reflect meaningful changes in health status in this population. This article summarizes the discussion at a joint workshop held September 5 and 6, 2013 in Silver Spring, Maryland, sponsored by the FDA and the American Association for the Study of Liver Diseases to develop guidance on diagnostic and therapeutic modalities for NASH. (Hepatology 2015;61:1392–1405)
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