PP/PP-HI/silica nanocomposites for HVDC cable insulation: Are silica clusters beneficial for space charge accumulation?

New potential High Voltage Direct Current (HVDC) cable insulation materials based on nanocomposites are developed in this study. The nanocomposites are produced by blending of polypropylene (PP), propylene-ethylene copolymer (PP–HI) and a modified fumed silica (A-silica) in a concentration of 1 and 2 wt %. The A-silica is successfully modified with (3-aminopropyl)triethoxysilane (APTES) via a solvent-free method, as proven by infrared spectroscopy, thermogravimetry and transmission electron microscope mapping. A-silica in the polymer matrix acts as a nucleating agent resulting in an increase of the crystallization temperature of the polymers and a smaller crystal size. Moreover, the silica addition modified the crystals morphology of the unfilled PP/PP-HI blend. The composite containing A-silica with 2 wt% contains bigger-size silica clusters than the composite filled with 1 wt%. The composite with the higher A-silica concentration shows lower space charge accumulation and a lower charge current value. Besides, much deeper traps and lower trap density are observed in the composite with 2 wt% A-silica addition compared to the one with a lower concentration. Surprisingly, the presence of silica clusters with dimensions of more than 200 nm exhibit a positive effect on reducing the space charge accumulation. However, the real cause of this improvement might be due to change of the electron distribution stemming from the amine-amine hydrogen bond formation, or the change of the chain mobility due to the presence of occluded polymer macromolecules constrained inside the high structure silica clusters. Both phenomena may lead to a higher energetic barrier of charge de-trapping, thus increasing the depth of the charge traps

High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint

Frameshift mutations frequently accumulate in microsatellite-unstable colorectal cancers (MSI CRCs) typically leading to downregulation of the target genes due to nonsense-mediated messenger RNA decay. However, frameshift mutations that occur in the 3' end of the coding regions can escape decay, which has largely been ignored in previous works. In this study, we characterized nonsense-mediated decay-escaping frameshift mutations in MSI CRC in an unbiased, genome wide manner. Combining bioinformatic search with expression profiling, we identified genes that were predicted to escape decay after a deletion in a microsatellite repeat. These repeats, located in 258 genes, were initially sequenced in 30 MSI CRC samples. The mitotic checkpoint kinase TTK was found to harbor decay-escaping heterozygous mutations in exon 22 in 59% (105/179) of MSI CRCs, which is notably more than previously reported. Additional novel deletions were found in exon 5, raising the mutation frequency to 66%. The exon 22 of TTK contains an A(9)-G(4)-A(7) locus, in which the most common mutation was a mononucleotide deletion in the A(9) (c.2560delA). When compared with identical non-coding repeats, TTK was found to be mutated significantly more often than expected without selective advantage. Since TTK inhibition is known to induce override of the mitotic spindle assembly checkpoint (SAC), we challenged mutated cancer cells with the microtubule-stabilizing drug paclitaxel. No evidence of checkpoint weakening was observed. As a conclusion, heterozygous TTK mutations occur at a high frequency in MSI CRCs. Unexpectedly, the plausible selective advantage in tumourigenesis does not appear to be related to SAC

Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing

This study examines the genes coding for enzymes involved in bovine milk oligosaccharide metabolism by comparing the oligosaccharide profiles with the expressions of glycosylation-related genes. Fresh milk samples (n = 32) were collected from four Holstein and Jersey cows at days 1, 15, 90 and 250 of lactation and free milk oligosaccharide profiles were analyzed. RNA was extracted from milk somatic cells at days 15 and 250 of lactation (n = 12) and gene expression analysis was conducted by RNA-Sequencing. A list was created of 121 glycosylation-related genes involved in oligosaccharide metabolism pathways in bovine by analyzing the oligosaccharide profiles and performing an extensive literature search. No significant differences were observed in either oligosaccharide profiles or expressions of glycosylation-related genes between Holstein and Jersey cows. The highest concentrations of free oligosaccharides were observed in the colostrum samples and a sharp decrease was observed in the concentration of free oligosaccharides on day 15, followed by progressive decrease on days 90 and 250. Ninety-two glycosylation-related genes were expressed in milk somatic cells. Most of these genes exhibited higher expression in day 250 samples indicating increases in net glycosylation-related metabolism in spite of decreases in free milk oligosaccharides in late lactation milk. Even though fucosylated free oligosaccharides were not identified, gene expression indicated the likely presence of fucosylated oligosaccharides in bovine milk. Fucosidase genes were expressed in milk and a possible explanation for not detecting fucosylated free oligosaccharides is the degradation of large fucosylated free oligosaccharides by the fucosidases. Detailed characterization of enzymes encoded by the 92 glycosylation-related genes identified in this study will provide the basic knowledge for metabolic network analysis of oligosaccharides in mammalian milk. These candidate genes will guide the design of a targeted breeding strategy to optimize the content of beneficial oligosaccharides in bovine milk

A Common SMAD7 Variant Is Associated with Risk of Colorectal Cancer: Evidence from a Case-Control Study and a Meta-Analysis

<div><h3>Background</h3><p>A common genetic variant, rs4939827, located in <em>SMAD7</em>, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.</p> <h3>Method and Findings</h3><p>We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all <em>P</em> for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.</p> <h3>Conclusion</h3><p>Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.</p> </div

Identification of Colorectal Cancer Related Genes with mRMR and Shortest Path in Protein-Protein Interaction Network

One of the most important and challenging problems in biomedicine and genomics is how to identify the disease genes. In this study, we developed a computational method to identify colorectal cancer-related genes based on (i) the gene expression profiles, and (ii) the shortest path analysis of functional protein association networks. The former has been used to select differentially expressed genes as disease genes for quite a long time, while the latter has been widely used to study the mechanism of diseases. With the existing protein-protein interaction data from STRING (Search Tool for the Retrieval of Interacting Genes), a weighted functional protein association network was constructed. By means of the mRMR (Maximum Relevance Minimum Redundancy) approach, six genes were identified that can distinguish the colorectal tumors and normal adjacent colonic tissues from their gene expression profiles. Meanwhile, according to the shortest path approach, we further found an additional 35 genes, of which some have been reported to be relevant to colorectal cancer and some are very likely to be relevant to it. Interestingly, the genes we identified from both the gene expression profiles and the functional protein association network have more cancer genes than the genes identified from the gene expression profiles alone. Besides, these genes also had greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying colorectal cancer genes. It has not escaped our notice that the method can be applied to identify the genes of other diseases as well

Biaxially oriented silica-polypropylene nanocomposites for HVDC film capacitors: Morphology-dielectric property relationships, and critical evaluation of the current progress and limitations

Dielectric polymer nanocomposites are considered as one of the most promising insulation material candidates for future capacitive energy storage applications, providing tailorability of charge trapping and transport properties at the nanometric level which is a key for increased dielectric performance of biaxially oriented polypropylene (BOPP) for metallized film capacitors in high-voltage direct current (HVDC) applications. In this study, a comprehensive investigation of morphology and dielectric performance of pilot-scale BOPP nanocomposites with hexamethyldisilazane (HMDS)-treated hydrophobic fumed silica nanoparticles was carried out, providing critical perspectives on the performance and challenges of PNCs for thin film capacitors also in a broader context. In non-oriented cast films, incorporation of nanosilica modified the crystallization kinetics and α/β-crystalline spherulitic morphology of polypropylene and reduced the accumulation of space charge under a DC electric field. The nanocomposites exhibited promising dispersion characteristics in the nano-scale, however, the low amount of micron-sized agglomerates inherently present in commercial fumed silica persisted in the compounds which can become critical for thin film applications. Subsequently, biaxial-stretching-induced morphology development and dielectric properties of silica-BOPP nanocomposites were evaluated, highlighting the role of precursor morphology and film processing in the silica-BOPP film morphology, defects and dielectric performance. Charge trapping and transport properties of silica-BOPP films were investigated by isothermal and thermally stimulated techniques under high DC electro-thermal stresses, indicating profound modification of the trap density of states brought about by nanosilica. This resulted in more homogeneous space charge distribution and reduced temperature- and field dependent DC conductivity at 100 °C in comparison to neat BOPP under moderate field stresses (&lt;200 V μm-1), while simultaneously maintaining low dielectric loss. However, the localized weak points caused by silica agglomerates still remain a challenge for the structural homogeneity and dielectric breakdown performance of thin BOPP films under extreme-field stress, hence emphasizing the need for further advancements in the agglomerate and PNC film morphology control to provide high-reliability nanodielectric capacitor thin films for practical HVDC film capacitor applications

Feasibility of Mini-Scale Injection Molding for Resource-Efficient Screening of PP-Based Cable Insulation Nanocomposites

This study presents a critical evaluation of the effect of two different sample manufacturing techniques on the morphological and dielectric properties of polypropylene (PP)-based nanocomposites, namely mini-scale injection molding (IM) vs. pilot-scale cast film extrusion. Polarized light microscopy revealed that the IM specimen morphology exhibited a layered 'skin-core' type morphology, largely differing from the spherulitic morphology of the corresponding extruded cast films. Higher degree of crystallinity in the IM specimens was evidenced by calorimetric and X-ray diffraction methods. The processing-dependent morphological differences were found to affect the isothermal charging current (ICC) and thermally stimulated depolarization current (TSDC) characteristics due to differences in charge mobility and trapping, thus making direct comparison of IM and cast film specimens non-straightforward. Nevertheless, mini-scale injection molding can be seen as a resource-efficient sample manufacturing method for facilitating early-stage screening of the best-performing material candidates, given that the morphological features are carefully taken into account

Synthesis and characterization of some water soluble Zn(ii) complexes with (E)-N-(pyridin-2-ylmethylene)arylamines that regulate tumour cell death by interacting with DNA

The synthesis and spectroscopic properties of nine water soluble zinc(II) complexes of (E)-N-(pyridin- 2-ylmethylene)arylamines (Ln) with the general formula [Zn(X)2(Ln)] (X = Cl−, Br−, I−; (1–8)) and [Zn(μ-N3)- (N3)(L3)]2 (9) are reported. The complexes were characterized by elemental analysis and their spectroscopic properties were studied using UV-Visible, fluorescence, IR and 1H NMR spectroscopies. The solid state structures of zinc(II) complexes 2–4 and 6–9 were established by single crystal X-ray crystallography. The majority of the structures are mononuclear with tetra-coordinate zinc centres (2–4, 6 and 7) except where L carries an additional donor atom capable of coordinating zinc (8), in which case the zinc atom has a distorted square pyramidal geometry. The centrosymmetric molecule of [Zn(μ-N3)(N3)(L3)]2 (9) is binuclear with the zinc atoms in a trigonal bipyramidal coordination environment. In general, the dichlorozinc derivatives 1, 3–5 and 8 exhibited moderately elevated in vitro cytotoxic potency towards the human epithelial cervical carcinoma (HeLa) cell line, with 4 as the best performer (IC50 value of 18 μM). Apoptosis-inducing activity, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showed that the zinc complexes interacted with DNA and thereby interfered the DNA binding of several transcription factors to its promoter sites, thus inhibiting gene transcription required for the biological activity of cells