Epoxide-diol pathway in the metabolism of 5H-dibenzo[b,f]-azepine (iminostilbene)

5H-Dibenzol[b,f]azepine-10,11-epoxide and 10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine were identified by gas chromatography-mass spectrometry in rat urine as the main biotransformation products in the metabolism of 5H-dibenzo[b,f]azepine (iminostilbene). The presence of these metabolites was confirmed in vitro by incubating iminostilbene with rat liver microsomal enzymes.     

Determination of Deoxynivalenol and Nivalenol in Wheat by Ultra-Performance Liquid Chromatography/Photodiode-Array Detector and Immunoaffinity Column Cleanup

An ultra-performance liquid chromatography (UPLC®) method has been developed for the simultaneous determination of deoxynivalenol (DON) and nivalenol (NIV) in wheat. Ground sample was extracted with water and the filtered extract was cleaned up through an immunoaffinity column containing a monoclonal antibody specific for DON and NIV. Toxins were separated and quantified by UPLC® with photodiode-array detector (λ?=?220 nm) in less than 3 min. Mean recoveries from blank wheat samples spiked with DON and NIV at levels of 100–2,000 μg/kg (each toxin) ranged from 85 to 95 % for DON and from 81 to 88 % for NIV, with relative standard deviations less than 7 %. Similar recoveries were observed from spiked samples when methanol/water (80:20, v/v) was used as extraction solvent. However, by using a wheat sample naturally contaminated with DON and NIV, the one-way analysis of variance (Student–Newman–Keuls test) between different extraction solvents and modes showed that water extraction provided a significant increase (P?<?0.001) in toxin concentrations (mean values of six replicate analyses) with respect to methanol/water (80:20, v/v). No significant difference was observed between shaking (60 min) and blending (3 min). The limit of detection (LOD) of the method was 30 μg/kg for DON and 20 μg/kg for NIV (signal-to-noise ratio 3:1). The immunoaffinity columns showed saturation of DON/NIV binding sites at levels higher than 2,000 ng in blank wheat extracts spiked with the corresponding amount of mycotoxin, as single mycotoxin or sum of DON and NIV. The range of applicability of the method was from LOD to 4,000 μg/kg, as single mycotoxin or sum of DON and NIV in wheat. The analyses of 20 naturally contaminated wheat samples showed DON contamination in all analyzed samples at level ranging from 30 to 2,700 μg/kg. NIV was detected in two samples at negligible toxin levels (up to 46 μg/kg). This is the first UPLC® method using immunoaffinity column cleanup for the simultaneous and sensitive determination of DON and NIV in wheat.     

In vivo lipolysis induced by heparin injection or fasting: a proton MR spectroscopy analysis of human plasma

The impact of induced lipolysis on the composition of plasma lipids is analyzed by proton magnetic resonance spectroscopy (MRS) in humans. The variations of the methylene and methyl resonances from lipids in lipoproteins are studied under two sets of lipolytic conditions: acute endovascular lipolysis induced by an intravenous injection of heparin and subacute lipolysis induced by short fasting. During acute lipolysis, the degradation of the very low density lipoproteins structures is well correlated to the modifications observed in the areas of CH₂ and CH₃ MRS signals. The comparison of regular spectra, spectra with water signal suppression, and spectra recorded with a spin-echo sequence provides information on the behavior of the different parts of the lipoproteins, that is, the neutral core, little affected by heparine-induced lipoprotein lipase (LPL) activation, and the surface layer supplying substrates to LPL. During 48 h of fasting, only limited modifications occur on the MR spectra, and lipolysis cannot be documented in details.Address for correspondence: CRMBM-CNRS, Faculté de Médecine, 27, bd Jean Moulin, 13005 Marseille, France.     

Gestion de réseau: État de la normalisation

The need for multi-media communication is currently rapidly increasing. This leads to a sharp increase in the number of public and private networks, and they must inter-operate in spite of their being heterogeneous. Mastering those networks is a complex but crucial task. This can only be achieved via good management. Thus, users have been impulsing a heavy thrust in the field of network management and especially its standardization. This paper focusses on the current status of network management standards in the main international bodies, highlighting the main points. It also describes some of France Telecom’s experiments concerning the implementation of the standards.     

Cloud condensation nuclei from the activation with ozone of soot particles sampled from a kerosene diffusion flame

Due to the exponential increase in aircraft traffic in recent decades, the role of soot particles emitted by aircraft engines on the radiative forcing needs to be addressed, and especially their interaction with clouds has to be better understood and quantified. In this work, we investigate the hygroscopic properties of fresh and aged soot sampled on line in a kerosene flame. The activated fraction (F_a) of size selected soot is measured by means of a variable supersaturation condensation nucleus counter at several heights above the burner (HAB), thereby probing soot particles with different residence times in the flame, i.e., different degrees of maturity. In order to simulate atmospheric aging, the activity of soot as cloud condensation nuclei is measured as a function of ozone exposure. We show that fresh soot is hydrophobic (F_a～0), while F_a increases when soot is exposed to ozone. The measurements depend on the HAB at which soot particles are sampled showing that activation of soot particles is related to their chemical composition. This study brings new results on the link between atmospheric aging of soot and its hygroscopic properties, which is of great interest for understanding the role of soot in the cloud formation.

Copyright © 2018 American Association for Aerosol Research     

ASGPR‐Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes

Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes.     

Trans10,cis15 18:2 Isolated from Beef Fat Does Not Have the Same Anti-Adipogenic Properties as Trans10,cis12–18:2 in 3T3-L1 Adipocytes

During ruminal biohydrogenation of α‐linolenic acid, a non‐conjugated non‐methylene interrupted dienoic acid is formed containing a t10 double bond, namely t10,c15–18:2. The present study was designed to examine whether t10,c15–18:2 would exert similar anti‐adipogenic effects compared to t10,c12–18:2 in 3T3‐L1 adipocytes. Differentiated 3T3‐L1 adipocytes were treated with 35 or 70 µM of LNA, t10,c12–18:2, t10,c15–18:2, or bovine serum albumin (BSA) vehicle control for 120 h. Cellular triacylglycerol and protein were quantified using commercial colorimetric kits. Cells were analyzed for fatty acid composition and gene expression using gas chromatography and quantitative PCR, respectively. Trans10,cis12–18:2 decreased (P < 0.05) the adipocyte triacylglycerol (TAG) content, which was mainly related to a reduction in saturated fatty acids (SFA; e.g., 16:0 and 15:0) and cis monounsaturated fatty acids (c‐MUFA; e.g., c9–16:1 and c9–18:1). Trans10,cis12 also decreased (P < 0.05) the expression of genes related to fatty acid synthesis (ACACA, FASN), delta‐9 desaturation (SCD1), fatty acid elongation (ELOVL5), and fatty acid uptake (LPL) and upregulated (P < 0.05) the expression of the rate‐liming enzyme involved in fatty acid β‐oxidation (CPT1). In contrast, LNA and t10,c15–18:2 did not affect the gene expression and cellular content of the TAG, SFA, c‐MUFA, or SCD1 indices in adipocytes. Our findings suggest that t10,c15–18:2, despite having structural similarity to t10,c12–18:2 (presence of a trans‐10 double bond), does not exert anti‐adipogenic effects in 3T3‐L1 adipocytes.     

A Technical Word- and Term-Translation Aid Using Noisy Parallel Corpora across Language Groups

Technical-term translation represents one of the most difficult tasks for human translators since (1) most translators are not familiar with terms and domain-specific terminology and (2) such terms are not adequately covered by printed dictionaries. This paper describes an algorithm for translating technical words and terms from noisy parallel corpora across language groups. Given any word which is part of a technical term in the source language, the algorithm produces a ranked candidate match for it in the target language. Potential translations for the term are compiled from the matched words and are also ranked. We show how this ranked list helps translators in technical-term translation. Most algorithms for lexical and term translation focus on Indo-European language pairs, and most use a sentence-aligned clean parallel corpus without insertion, deletion or OCR noise. Our algorithm is language- and character-set-independent, and is robust to noise in the corpus. We show how our algorithm requires minimum preprocessing and is able to obtain technical-word translations without sentence-boundary identification or sentence alignment, from the English–Japanese awk manual corpus with noise arising from text insertions or deletions and on the English–Chinese HKUST bilingual corpus. We obtain a precision of 55.35% from the awk corpus for word translation including rare words, counting only the best candidate and direct translations. Translation precision of the best-candidate translation is 89.93% from the HKUST corpus. Potential term translations produced by the program help bilingual speakers to get a 47% improvement in translating technical terms.     

A search space “cartography” for guiding graph coloring heuristics

We present a search space analysis and its application in improving local search algorithms for the graph coloring problem. Using a classical distance measure between colorings, we introduce the following clustering hypothesis: the high quality solutions are not randomly scattered in the search space, but rather grouped in clusters within spheres of specific diameter. We first provide intuitive evidence for this hypothesis by presenting a projection of a large set of local minima in the 3D space. An experimental confirmation is also presented: we introduce two algorithms that exploit the hypothesis by guiding an underlying Tabu Search (TS) process. The first algorithm (TS-Div) uses a learning process to guide the basic TS process toward as-yet-unvisited spheres. The second algorithm (TS-Int) makes deep investigations within a bounded region by organizing it as a tree-like structure of connected spheres. We experimentally demonstrate that if such a region contains a global optimum, TS-Int does not fail in eventually finding it. This pair of algorithms significantly outperforms the underlying basic TS algorithm; it can even improve some of the best-known solutions ever reported in the literature (e.g. for dsjc1000.9).     

A numerical hydrodynamic and thermal characterization of an inter-strata liquid cooling solution for 3D ICs

A novel integrated thermal management solution is proposed to alleviate hot spots in a contemporary 3D IC architecture. The solution employs a series of integrated microchannels, interconnected through each stratum by through silicon fluidic vias (TSFVs), and permits the transfer of heat, via a coolant, from hot to cold zones. This microfluidic system is driven by an integrated AC electrokinetic pump embedded in the channel walls. Recent advancements in electrokinetic micropump technology have allowed greater increases in fluid velocity (mm/s) while operating within the voltage constraints of a 3D IC. This paper presents a 2D simulation of an electrokinetic micropump operating at V_pp = 1.5 V in a 40 μm channel and examines its velocity profile for six frequencies in the range 100 ≤ ω ≤ 100 MHz. An optimum frequency of 100 kHz was established within this range and this was further examined with a constant heat flux of 186 W/cm2 imposed on the wall for an inlet fluid temperature of 40°C. Temperature profiles are presented at the channel-silicon interface and compared with theory.