Synthesis and spectroscopic characterization of new iron(III) complexes of S-Alkyl/Aryl dithiocarbazates of 5-methyl-3-formylpyrazole and 5-methyl-3-formylpyrazolyl-thiosemicarbazones

New iron (III) complexes of S-methyl-βN-(5-methylpyrazole-3-yl)methylenedithiocarbazate, S-benzyl-β-N-β-(5-methylpyrazole-3-yl)methylenedithiocarbazate, 5-methyl-3-formylpyrazole-3-pyrrolidinylthiosemicarbazone, and 5-methyl-3-formylpyrazole-⁴N-benzylthiosemicarbazone have been synthesized and physicochemically characterized by elemental analyses, magnetic moment measurements (polycrystalline state), electronic, IR, and EPR spectra, as well as conductance measurements, are used to confirm the coordination geometry. The spectral studies reveal the low-spin distorted octahedral structure of the iron (III) complexes containing two uninegative tridentate ligands with NNS donor sites, where the EPR data confirm the presence of a spin — paired iron (III) with d _xz ² d _yz ² d _xy ¹ configuration in the ground state. The article is published in the original.     

The relevance of DEA benchmarking information and the Least-Distance Measure

Efficiency analysis is performed not only to estimate the current level of efficiency, but also to provide information on how to remove inefficiency, that is, to obtain benchmarking information. Data Envelopment Analysis (DEA) was developed in order to satisfy both objectives and the strength of its benchmarking analysis gives DEA a unique advantage over other methodologies of efficiency analysis. This study proposes the use of the Least-Distance Measure in order to obtain the shortest projection from the evaluated Decision Making Unit (DMU) to the strongly efficient production frontier, thus allowing an inefficient DMU to find the easiest way to improve its efficiency. In addition to producing reasonable benchmarking information, the proposed model provides efficiency values which satisfy the general requirements that every well-defined efficiency measure should meet.     

Modification of both the electrophilic center and substituents on the nonleaving group in pyridinolysis of O-4-nitrophenyl benzoate and thionobenzoates

A kinetic study is reported for reactions of 4-nitrophenyl benzoate (1c) and O-4-nitrophenyl X-substituted thionobenzoates (2a-e) with a series of pyridines in 80 mol % H2O/20 mol % dimethyl sulfoxide (DMSO) at 25.0 +/- 0.1 degrees C. O-4-Nitrophenyl thionobenzoate (2c) is more reactive than its oxygen analogue 1c toward all the pyridines studied. The Br?nsted-type plot is linear with beta(nuc)=1.06 for reactions of 1c but curved for the corresponding reactions of 2c with beta(nu)c decreasing from 1.38 to 0.38 as the pyridine basicity increases, indicating that the reaction mechanism is also influenced on changing the electrophilic center from C=O to C=S. The curvature center of the curved Br?nsted-type plots (defined as pK(a)(o)) occurs at pKa = 9.3 regardless of the electronic nature of the substituent X in the nonleaving group. The Hammett plot for reactions of 2a-e with 4-aminopyridine is nonlinear, i.e., the substrates having an electron-donating substituent exhibit negative deviations from the Hammett plot. However, the Yukawa-Tsuno plot for the same reactions exhibits good linear correlation, indicating that the negative deviations shown by these substrates arise from stabilization of the ground state through resonance interaction between the electron-donating substituent X and the C=S bond.     

Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue

In this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12^−/−), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12^−/− livers. Surprisingly, the exposure of Acot12^−/− hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin identification (BioID) analysis, suggested that ACOT12 may directly interact with vacuolar protein sorting-associated protein 33A (VPS33A) and play a role in vesicle-mediated cholesterol trafficking and the process of lysosomal degradation of cholesterol in hepatocytes. In summary, in this study, we found that ACOT12 deficiency is responsible for the pathogenesis of NAFLD through the accumulation of acetyl-CoA and the stimulation of DNL and cholesterol via activation of PPARα and inhibition of cholesterol trafficking.Subject terms: Gene expression, Disease model     

Functional magnetic resonance cholangiography with Gd-EOB-DTPA: A study in healthy volunteers

Purpose

To describe the patterns of bile distribution in the biliary tree, duodenum, jejunum, and stomach, and to determine the gallbladder ejection fraction (GBEF) by using functional magnetic resonance cholangiography (MRC) with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in healthy volunteers.

Materials and Methods

Forty subjects were included in this study. After conventional MRC, pre-fatty meal MRC (PRFM) was obtained at 30, 40, 50, and 60 min after contrast agent injection. Then, post-fatty meal MRC (POFM) was obtained every 10 min for 1 h. We assessed the PRFM and POFM for opacification of contrast agent in the first- and second-order intrahepatic ducts (IHDs) and the common bile duct (CBD). Contrast agent opacification in the cystic duct was assessed, and the percentage volume of contrast agent filling in the gallbladder (GB) was calculated on PRFM. We calculated the GBEF and assessed the presence of contrast agent in the GB, duodenum, jejunum, and stomach.

Results

Thirty-six (90%) subjects showed grade 3 CBD opacification (visible contrast and well-defined bile duct border) on 60-min PRFM. Thirty-four (85%) subjects showed grade 3 first-order IHD opacification on 60-min PRFM. All (100%) subjects showed cystic duct opacification of contrast agent, and the average percentage volume of contrast agent filling in the GB was 68.81% ± 16.84% on 60-min PRFM. The GBEF at 30-min POFM was 35.00% ± 18.26%. Ten (25%) subjects had no contrast agent in the stomach and small bowel on all PRFMs. Twelve (30%) subjects had contrast medium in the stomach on PRFM and/or POFM.

Conclusions

Functional MRC with Gd-EOB-DTPA can allow determining the distribution of bile in the biliary tree and small intestine, as well as the GBEF.     

Structure of the stapled p53 peptide bound to Mdm2

Mdm2 is a major negative regulator of the tumor suppressor p53 protein, a protein that plays a crucial role in maintaining genome integrity. Inactivation of p53 is the most prevalent defect in human cancers. Inhibitors of the Mdm2-p53 interaction that restore the functional p53 constitute potential nongenotoxic anticancer agents with a novel mode of action. We present here a 2.0 ? resolution structure of the Mdm2 protein with a bound stapled p53 peptide. Such peptides, which are conformationally and proteolytically stabilized with all-hydrocarbon staples, are an emerging class of biologics that are capable of disrupting protein-protein interactions and thus have broad therapeutic potential. The structure represents the first crystal structure of an i, i + 7 stapled peptide bound to its target and reveals that rather than acting solely as a passive conformational brace, a staple can intimately interact with the surface of a protein and augment the binding interface.     

A high isolation W-band MMIC drain type cascode single balanced mixer

We present a high isolation W-band MMIC drain type cascode single balanced mixer of high LO-to-RF isolation and wide band with conversion characteristic using the high directivity monolithic tandem couplers and 0.1 μm GaAs-based metamorphic high electron mobility transistors (MHEMTs). The fabricated mixer consists of two cascode MHEMT mixers and two tandem couplers using the air-bridge crossovers. We establish a drain type cascode mixer structure where the LO signal is applied to the drain port in the mixing component of common source MHEMT circuit. The tandem coupler exhibits good couplings (2.92-3.8 dB), low return losses (−32.7 dB), and isolations (15.4-39.2 dB) in a wide bandwidth of 75-110 GHz. The mixer shows a conversion loss of 9.8 dB at 94 GHz, an output P1dB of −14.8 dBm at LO frequency of 94.542 GHz, and LO-to-RF isolations of 29.5-39.5 dB at 94-100 GHz.     

Silica xerogel films hybridized with carbon nanotubes by single step sol–gel processing

Synthesis of multi-walled carbon nanotubes (MWCNTs) doped silica xerogel films was reported in this work. A crucial step of introducing MWCNTs was achieved by functionalizing them by acid treatment to form stable and homogenous SiO₂/MWCNTs sol. Scanning electron microscopy showed spherical particles in honeycomb network structure for undoped xerogel films whereas dispersion and wrapping of MWCNTs in silica matrix was observed for MWCNTs doped films. Various bond formations during the sol–gel process and surface modification were confirmed using Fourier transform infra-red and detailed study on the chemical bonding state of the films was carried out using X-ray photoelectron spectroscopy. Nanoindentation studies showed that the mechanical properties of MWCNTs doped xerogel film increase dramatically: higher modulus (E = 2.127 ± 0.095 GPa) and hardness (H = 0.035 ± 0.017 GPa) values than those of pristine xerogel film (E = 0.234 ± 0.058 GPa, H = 0.01 ± 0.003 GPa).     

Dynamic condensation in a damped system through rational selection of primary degrees of freedom

Various system reduction methods have been proposed to calculate eigenvalues and eigenvectors with computational efficiency. In the case of system condensation, the method of selecting proper primary degrees of freedom (PDOFs) is crucial because they are closely related to the accuracy and reliability of eigensystem prediction in a reduced system. Although reasonable selection methods for PDOFs have been proposed for undamped systems, these methods cannot be directly extended to damped systems. We propose a PDOF selection method for a damped system. The proposed method is based on the ratio of DOF-wise energy distributions. In order to estimate the energy distribution of the structure, Ritz vectors are obtained using a two-sided Lanczos algorithm. Energy distribution matrices are calculated from the obtained Ritz vectors. Then, degrees of freedom (DOFs) corresponding to the lowest Rayleigh quotients are selected as the PDOFs. The efficiency and reliability of the proposed method are demonstrated using numerical examples.