Focused grid‐based resampling for protein docking and mapping

The fast Fourier transform (FFT) sampling algorithm has been used with success in application to protein‐protein docking and for protein mapping, the latter docking a variety of small organic molecules for the identification of binding hot spots on the target protein. Here we explore the local rather than global usage of the FFT sampling approach in docking applications. If the global FFT based search yields a near‐native cluster of docked structures for a protein complex, then focused resampling of the cluster generally leads to a substantial increase in the number of conformations close to the native structure. In protein mapping, focused resampling of the selected hot spot regions generally reveals further hot spots that, while not as strong as the primary hot spots, also contribute to ligand binding. The detection of additional ligand binding regions is shown by the improved overlap between hot spots and bound ligands. © 2016 Wiley Periodicals, Inc.     

Assay of actinides in human urine by rapid method

A method using DGA resin (N,N,N′,N′-tetra-n-octyldiglycolamide on an inert support) was developed for the rapid analysis of actinides in urine samples. Samples acidified with HCl to 4 M were loaded directly (without digestion) onto a DGA column. Actinides were stripped simultaneously, α-sources were prepared by co-precipitation with NdF₃. Americium, plutonium and uranium were separated with acceptable high recoveries (40–80%). The americium, plutonium and uranium content of 100–200 ml urine samples was determined within 24 h with detection limits as low as 0.01 Bq l^?1. Based on model experiments using ¹⁴C-spiked urea, it was proven that high urea content can affect americium separation deleteriously due to irreversible fixing of americium on DGA resin.     

Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging

Negative ion desorption electrospray ionization (DESI) was used for the analysis of an ex vivo tissue sample set comprising primary colorectal adenocarcinoma samples and colorectal adenocarcinoma liver metastasis samples. Frozen sections (12 μm thick) were analyzed by means of DESI imaging mass spectrometry (IMS) with spatial resolution of 100 μm using a computer-controlled DESI imaging stage mounted on a high resolution Orbitrap mass spectrometer. DESI-IMS data were found to predominantly feature complex lipids, including phosphatidyl-inositols, phophatidyl-ethanolamines, phosphatidyl-serines, phosphatidyl-ethanolamine plasmalogens, phosphatidic acids, phosphatidyl-glycerols, ceramides, sphingolipids, and sulfatides among others. Molecular constituents were identified based on their exact mass and MS/MS fragmentation spectra. An identified set of molecules was found to be in good agreement with previously reported DESI imaging data. Different histological tissue types were found to yield characteristic mass spectrometric data in each individual section. Histological features were identified by comparison to hematoxylin-eosin stained neighboring sections. Ions specific to certain histological tissue types (connective tissue, smooth muscle, healthy mucosa, healthy liver parenchyma, and adenocarcinoma) were identified by semi-automated screening of data. While each section featured a number of tissue-specific species, no potential global biomarker was found in the full sample set for any of the tissue types. As an alternative approach, data were analyzed by principal component analysis (PCA) and linear discriminant analysis (LDA) which resulted in efficient separation of data points based on their histological types. A pixel-by-pixel tissue identification method was developed, featuring the PCA/LDA analysis of authentic data set, and localization of unknowns in the resulting 60D, histologically assigned LDA space. Novel approach was found to yield results which are in 95% agreement with the results of classical histology. KRAS mutation status was determined for each sample by standard molecular biology methods and a similar PCA/LDA approach was developed to assess the feasibility of the determination of this important parameter using solely DESI imaging data. Results showed that the mutant and wild-type samples fully separated. DESI-MS and molecular biology results were in agreement in 90% of the cases.     

Recovery of low-temperature electron-irradiated lutetium

The annealing spectrum of electron-irradiated Lu has been studied between 14 and 135 K and a tentative interpretation of the observed structure given. A comparison with other irradiated h.c.p. metals indicates that the c/a-ratio might be an important parameter for the determination of the interstitial-atom mobility.     

Molecular structures of (SiCl3)2CH2 and (SiCl3)2CCl2 as studied by electron diffraction

An electron diffraction analysis of the molecular structures of 1,1,1,3,3,3-hexachloro-1,3-disilapropane and octachloro-1,3-disilapropane has been carried out. Deviations from the staggered conformation are indicated. The data may be approximated by models with C₂ symmetry and a small tilt of the SiCl₃ groups. The main bond lengths (r_g) and bond angles obtained for (SiCl₃)₂ CH₂ are: SiCl, 202.7(4); SiC, 186.6(6); CH, 109.8(24) pm, ClSiCl, 107.9(1); SiCSi, 118.3(7)°; and for (SiCl₃)₂CCl₂: SiCl, 202.0(4); SiC, 190.2(9); CCl, 179.6(9) pm; ClSiCl, 109.5(1); SiCSi, 120.6(9); ClCCl, 110.9(16); SiCCl, 106.3(3)°.     

Variation of long-lived free radicals responsible for the EPR native signal in bone of aged or diseased human females and ovariectomized adult rats

The purpose of this study was to gain insights into the variations seen in the electron paramagnetic resonance (EPR) spectroscopy of the native signals of teeth and bones used for retrospective dosimetry measurements. We determined that changes occur in the long-lived free radicals responsible for the native signal of cortical bone in aging or diseased human females and aged ovariectomized rats. This was done by measuring the magnitude of the broad (BC) and narrow (NC) components of the native EPR signal of bone following chemical extraction, aging, crushing and thermal annealing. Bone from the upper midshaft of femora of young (17-34 years old, n=5) and elderly (70-92 years old, n=18) females was examined. The results showed that the elderly women had significantly higher BC than the younger women (P<0.01). A similar interpretation was made of the data from an aging female rat osteoporosis model. The results for the NC signals were similar. Finally, dramatic decreases in both NC and BC signals were seen in HIV positive and uncontrolled diabetic (one each) patients indicating the need for studying this signal for a broad spectrum of metabolic disorders. Experiments were performed which strongly indicate that iron liganded with organic molecules is the source of the BC signal. Finally, the accuracy achieved in this study indicates that resolving the dosimetric signal (g=2.0018) should be improved by subtraction of the deconvoluted NC and BC signals from the original spectrum.