Morphology of drawn syndiotactic polypropylene films

Morphological studies were conducted to investigate the drawability of melt-quenched (MQ) and slowly cooled (MSC) films of syndiotactic polypropylene (sPP) with a high syndiotactic pentad fraction. Transmission electron microscopy (TEM) using the ruthenium tetraoxide staining and ultrathin sectioning method revealed that amorphous chains as the matrix of MQ film played a role in drawability of the film by their alignment to machine direction (MD) and partial crystallizations into nanofibrils. On the other hand, the initial strain induced, rotations of clusters of long lamellar crystals as the major entity of MSC film accompanying breaks of long lamellae and formation of crazes and microvoids at the cluster boundary. Compared with a homogeneous thinning of MQ film by drawing, ca. 100 nm-thick layer slips along MD and parallel to the film surface took place in MSC film. This gave rise to the formation of V-shaped bent lamellar morphology and their further break into a smaller cluster of stacked lamellae which were aligned oblique by ca. 35 from MD. With elongation, some nanofibrils formed from chains generated by the partial breaks of lamellae are aligned perpendicular to the remained oblique lamellae and others parallel to MD in region where lamellar morphology almost disappeared. No chain slips in the nanofibrils can be related to a low elongation at break, i.e. a low ductility of sPP films. The lower elongation at break for MSC film than for MQ one can be interpreted by microvoids initially formed in the neck region and later moved to the fully drawn part, the microvoids initiating the break of the drawn film

Synthesis and properties of radiopaque polymer hydrogels: polyion complexes of copolymers of acrylamide derivatives having triiodophenyl and carboxyl groups and p-styrene sulfonate and polyallylamine

In order to pursue a possibility of application of radiopaque polymer hydrogels to vascular embolization, studies were done on synthesis of iodine-containing copolyanions and properties of their hydrogels with polycation via formation of polyion complexes. Acrylamide derivatives having triiodophenyl and carboxyl groups were synthesized and copolymerized with sodium styrene sulfonate at various molar ratios of initiator to monomer and temperatures. Hydrogels were prepared by mixing aqueous solutions of the obtained radiopaque copolyanions and polyallylamine. Embolization was examined by injection of these hydrogels into vein of a removed porcine kidney as a preliminary test for transcatheter arterial embolization (TAE) for hepatocellular carcinoma. It was found that the hydrogels prepared from the copolycation obtained under particular conditions give high X-ray contrasts of the vein and remained there, though copolycations with low molecular weights had a tendency to drain through the capillaries to the peripheral tissues. It is therefore concluded that the hydrogels examined in the present study are promising for vascular embolization

A manufacturing framework for capability-based product-service systems design

Manufacturers aim to design product-service systems (PSS) which integrate services with products to attain sustained competitive advantage from a life cycle perspective. PSS design should be customer-adjusted solutions which are aligned to integrated stakeholders' capabilities, a subject which the extant literature has not sufficiently addressed. This paper proposes a systematic framework for the PSS solution provider to address this aim and operationalizes this through software developed for PSS design which models stakeholders' individual activities and simulates their occurrences depending on their relations. The framework stresses that integrated stakeholders' capabilities define continuing ability to generate a desired operational outcome for the customers. The paper reports a PSS design case for a laser system manufacturer and then applies the framework to it. The industrial experts' views on this framework reveal that it helps to develop PSS design from a holistic systems approach which facilitates a change in the designer's mindset from product-centric to systems-centric. The level of trust and transparency required for this framework is argued to be absent in most industrial sectors, being one of the foremost limitations for implementation of PSS

Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas

<p>Abstract</p> <p>Background</p> <p>Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series. Furthermore, we tested the efficacy of drugs targeting these molecules, as single agents or in combination with gemcitabine, the standard therapeutic agent against BTC.</p> <p>Methods</p> <p>Immunohistochemistry, FISH and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs), extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell proliferation of different EGFR/HER2 pathway inhibitors as single agents or in combination with gemcitabine was investigated on BTC cell lines. Western blot analyses were performed to investigate molecular mechanisms of targeted drugs.</p> <p>Results</p> <p>EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs. P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower extent in ECCs and GBCs (<46%), indicating EGFR pathway activation. HER2 is overexpressed in 10% of GBCs (with genomic amplification), and 26.3% of ECCs (half of which has genomic amplification). EGFR or its signal transducers are mutated in 26.5% of cases: 4 samples bear mutations of PI3K (8.2%), 3 cases (6.1%) in K-RAS, 4 (8.2%) in B-RAF, and 2 cases (4.1%) in PTEN, but no loss of PTEN expression is detected. EGI-1 cell line is highly sensitive to gemcitabine, TFK1 and TGBC1-TKB cell lines are responsive and HuH28 cell line is resistant. In EGI-1 cells, combination with gefitinib further increases the antiproliferative effect of gemcitabine. In TFK1 and TGBC1-TKB cells, the efficacy of gemcitabine is increased with addiction of sorafenib and everolimus. In TGBC1-TKB cells, lapatinib also has a synergic effect with gemcitabine. HuH28 becomes responsive if treated in combination with erlotinib. Moreover, HuH28 cells are sensitive to lapatinib as a single agent. Molecular mechanisms were confirmed by western blot analysis.</p> <p>Conclusion</p> <p>These data demonstrate that EGFR and HER2 pathways are suitable therapeutic targets for BTCs. The combination of gemcitabine with drugs targeting these pathways gives encouraging results and further clinical studies could be warranted.</p

Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells. [R. Pero* corresponding author]

Inducible nitric oxide synthase (iNOS) expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in iNOS disregulation. We undertook this study to investigate possible chromatin changes occurring early during iNOS gene activation as a direct consequence of Hp???gastric cells interaction. We show that Hp infection is followed by different expression and chromatin modifications in gastric cells including (1) activation of iNOS gene expression, (2) chromatin changes at iNOS promoter including decreased H3K9 methylation and increased H3 acetylation and H3K4 methylation levels, (3) selective release of methyl-CpG-binding protein 2 from the iNOS promoter. Moreover, we show that Hp-induced activation of iNOS is delayed, but not eliminated, by the treatment with LSD1 inhibitors. Our data suggest a role for specific chromatin-based mechanisms in the control of human iNOS gene expression upon Hp exposure

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p