Numerical Simulation of Magnetic Nanoparticles Targeted at an Atherosclerotic Lesion in the Left Coronary Artery of Patient

ABSTRACT A numerical investigation simulating feasibility of magnetic drug targeting (MDT) at an atherosclerotic lesion of the left coronary artery of a patient using iron nano-particles coated with a therapeutic agent is reported. Progression of a plaque in the left coronary artery over a six month period was previously determined by intravascular ultrasound (IVUS). The site where the progression is active is located on the leeward side of the plaque. The proximal segment of the left coronary artery including the lesion was reconstructed by our 3D IVUS technique, and a Doppler measurement provided velocity waveforms in the lumen. These data are used to simulate blood flow employing computational fluid dynamics (CFD). Wall shear stress (WSS) and flow pathlines show that few nanoparticles would reach the active lesion region of the plaque. Therefore, MDT is considered as a possible effective therapy. Numerical investigations are performed to examine the feasibility for treatment by modeling hypothetical magnet fields, iron nano-particles, and coronary artery flow conditions. The magnetic field in the lesion segment produced by a permanent magnet located outside the lumen is calculated. The motion of the nanoparticles in the segment is a combined result of the velocities produced by hemodynamic and magnetic forces. Various particles and magnets are investigated in the simulations. Two kinds of results are presented: the distribution of the magnetic force produced by the magnets, and the quantity of captured particles at the lesion during various time intervals (number of heart beats)

Identify submitochondria and subchloroplast locations with pseudo amino acid composition: Approach from the strategy of discrete wavelet transform feature extraction

AbstractIt is very challenging and complicated to predict protein locations at the sub-subcellular level. The key to enhancing the prediction quality for protein sub-subcellular locations is to grasp the core features of a protein that can discriminate among proteins with different subcompartment locations. In this study, a different formulation of pseudoamino acid composition by the approach of discrete wavelet transform feature extraction was developed to predict submitochondria and subchloroplast locations. As a result of jackknife cross-validation, with our method, it can efficiently distinguish mitochondrial proteins from chloroplast proteins with total accuracy of 98.8% and obtained a promising total accuracy of 93.38% for predicting submitochondria locations. Especially the predictive accuracy for mitochondrial outer membrane and chloroplast thylakoid lumen were 82.93% and 82.22%, respectively, showing an improvement of 4.88% and 27.22% when other existing methods were compared. The results indicated that the proposed method might be employed as a useful assistant technique for identifying sub-subcellular locations. We have implemented our algorithm as an online service called SubIdent (http://bioinfo.ncu.edu.cn/services.aspx)

PMeS: Prediction of Methylation Sites Based on Enhanced Feature Encoding Scheme

Protein methylation is predominantly found on lysine and arginine residues, and carries many important biological functions, including gene regulation and signal transduction. Given their important involvement in gene expression, protein methylation and their regulatory enzymes are implicated in a variety of human disease states such as cancer, coronary heart disease and neurodegenerative disorders. Thus, identification of methylation sites can be very helpful for the drug designs of various related diseases. In this study, we developed a method called PMeS to improve the prediction of protein methylation sites based on an enhanced feature encoding scheme and support vector machine. The enhanced feature encoding scheme was composed of the sparse property coding, normalized van der Waals volume, position weight amino acid composition and accessible surface area. The PMeS achieved a promising performance with a sensitivity of 92.45%, a specificity of 93.18%, an accuracy of 92.82% and a Matthew’s correlation coefficient of 85.69% for arginine as well as a sensitivity of 84.38%, a specificity of 93.94%, an accuracy of 89.16% and a Matthew’s correlation coefficient of 78.68% for lysine in 10-fold cross validation. Compared with other existing methods, the PMeS provides better predictive performance and greater robustness. It can be anticipated that the PMeS might be useful to guide future experiments needed to identify potential methylation sites in proteins of interest. The online service is available at http://bioinfo.ncu.edu.cn/inquiries_PMeS.aspx

The Overseeing Mother: Revisiting the Frontal-Pose Lady in the Wu Family Shrines in Second Century China

Located in present-day Jiaxiang in Shandong province, the Wu family shrines built during the second century in the Eastern Han dynasty (25–220) were among the best-known works in Chinese art history. Although for centuries scholars have exhaustively studied the pictorial programs, the frontal-pose female image situated on the second floor of the central pavilion carved at the rear wall of the shrines has remained a question. Beginning with the woman’s eyes, this article demonstrates that the image is more than a generic portrait (“hard motif ”), but rather represents “feminine overseeing from above” (“soft motif ”). This synthetic motif combines three different earlier motifs – the frontal-pose hostess enjoying entertainment, the elevated spectator, and the Queen Mother of the West. By creatively fusing the three motifs into one unity, the Jiaxiang artists lent to the frontal-pose lady a unique power: she not only dominated the center of the composition, but also, like a divine being, commanded a unified view of the surroundings on the lofty building, hence echoing the political reality of the empress mother’s “overseeing the court” in the second century during Eastern Han dynasty

Solvent effect on the debromination/dehydrobromination of bromo-damascone

The dehydrogenative synthesis of -damascenone from -damascone via the related allyl bromide intermediate was studied in depth. The requisite dehydrobromination thereof was found strongly solvent system dependent. Under respective conditions, the product was identified as dehydrogenation-derived a, 4-alkoxy-derived b and 4-oxo-derived c, accordingly. In addition, the conversion from b to a was successfully accomplished, thereby offering an alternative access (with one step more) to reach -damascenone. Copyright (c) 2016 John Wiley &amp; Sons, Ltd.</p

Cobalt-catalyzed direct transformation of aldehydes to esters: the crucial role of an enone as a mediator

An oxidative esterification of aldehydes with alkanols catalyzed by an in situ generated low-valent cobalt system has been developed using an enone as a mild oxidant. Mechanistic studies revealed that it proceeds through a Co(i)-catalyzed hydrogen-transfer route, wherein the -vinyl moiety in the bidentate enone functions as a hydride acceptor. Meanwhile, Co(i)-catalyzed formyl C-H activation occurred as a competing reaction leading to aldehyde dimerization. The occurrence of the usually kinetically disfavored hydride transfer step therein was significantly increased in the presence of an enone reacting as a hydride transfer initiator

Cobalt-Catalyzed Chemoselective Transfer Hydrogenation of C=C and C=O Bonds with Alkanols

An environmentally benign protocol of chemoselective transfer hydrogenation of C=C and C=O bonds with alkanols under base-free conditions is developed by this study, wherein the cobalt-bidentate phosphine catalyst precursor is commercially available and the active low-valent Co species could be generated in-situ. For the conjugation enones, the vinyl group is selectively reduced, whereas with nonconjugated alkenones, the selectivity is changed to the carbonyl group. Besides, orthoalkenyl-benzaldehydes/imines are well tolerated, and the reduction solely occurs at the C=O/C=N site with this protocol

Cobalt(II)/N,N',N''- Trihydroxyisocyanuric Acid Catalyzed Aerobic Oxidative Esterification and Amidation of Aldehydes

A protocol for a Co-II/N,N',N''-trihydroxyisocyanuric acid (THICA)-catalyzed aerobic oxidative esterification and amidation of aldehydes has been developed. Preliminary insight into the mechanism indicates that such an oxidative C-O/N cross-coupling reaction proceeds by masking the aldehyde in a nucleophilic addition reaction with an alkoxy/amino source, thereby keeping the highly reactive formyl group from undesired oxidation. This protocol for the oxidative esterification and amidation of aldehydes proceeds through two different pathways that are characterized by the intrinsic nucleophilicity of the alkanol and amine sub-strates The former occurs in the presence of p-CH3C6H4SO3H as a cocatalyst and orthoformates as the alkoxy sources, instead of alkanols, to efficiently afford the transient acetals. In contrast, the coupling of the more nucleophilic amines with aldehydes renders a readily accessible cross-coupling reaction that occurs without any cocatalyst but is limited by the potential inhibition of THICA upon nucleophilic substitution by an amine. Consequently, only sterically hindered amines were tolerated in this catalytic system, whereas further condensation occurred in the presence of primary amines to lead to imines

Systematic Analysis and Prediction of Pupylation Sites in Prokaryotic Proteins

<div><p>Prokaryotic ubiquitin-like protein (Pup) is the first identified prokaryotic protein that is functionally analogous to ubiquitin. Recent studies have shed light on the Pup activation and conjugation to target proteins to be a signal for the selective degradation proteins in <i>Mycobacterium tuberculosis</i> (Mtb). By covalently conjugating the Pup, pupylation functions as a critical post-translational modification (PTM) conserved in actinomycetes. Detecting pupylation sites is crucial and fundamental for understanding the molecular mechanisms of Pup. Yet comparative studies with other PTM suggest that the development of accurate and complete repertories of pupylation is still in its early stages. Unbiased screening for pupylation sites by experimental methods is time consuming and expensive; <i>in silico</i> prediction can provide highly potential candidates and reduce the number of potential candidates that require further <i>in vivo</i> or <i>in vitro</i> confirmation. Here, we present an effective classifier of PupPred for predicting pupylation sites, which shows better performance than existing classifiers. Importantly, this work not only investigates the sequential, structural and evolutionary hallmarks around pupylation sites but also compares the differences of pupylation and ubiquitylation from the environmental, conservative and functional characterization of substrates. These prediction and analysis results may be helpful for further experimental investigation of degradation proteins in prokaryotes. Finally, the PupPred server is available at <a href="http://bioinfo.ncu.edu.cn/PupPred.aspx" target="_blank">http://bioinfo.ncu.edu.cn/PupPred.aspx</a>.</p></div

GO annotations for the highly pupylated proteins from prokaryotes proteome (red bars) with occurrence of >5% (Bonferroni corrected) as compared to the highly ubiquitylated proteins from eukaryotes proteome (green bars).

<p>Top 10 (whenever available) GO Slim terms are shown. (A) Molecular function; (B) Biological process; (C) Cellular component. The proteins are arranged in order of the decreasing fraction of proteins with a specific GO annotation present in the predicted highly pupylated dataset. <i>P</i>-values were calculated using the Fisher’s exact test (two tails) and corrected for multiple testing. ***<i>P</i><0.0001; **<i>P</i><0.001; *<i>P</i><0.05.</p