Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: A comparison of symptomatic and asymptomatic individuals

Background and purpose: Inflammation is a risk factor the vulnerable atheromatous plaque. This can be detected in vivo on high-resolution magnetic resonance (MR) imaging using a contrast agent, Sinerem™, an ultra-small super-paramagnetic iron oxide (USPIO). The aim of this study was to explore whether there is a difference in the degree of MR defined inflammation using USPIO particles, between symptomatic and asymptomatic carotid plaques. We report further on its T1 effect of enhancing the fibrous cap, which may allow dual contrast resolution of carotid atheroma. Methods: Twenty patients with carotid stenosis (10 symptomatic and 10 asymptomatic) underwent multi-sequence MR imaging before and 36 h post-USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change across all quadrants were compared between the two groups. Results: Symptomatic patients had significantly more quadrants with a signal drop than asymptomatic individuals (75% vs. 32%, p < 0.01). Asymptomatic plaques had more quadrants with signal enhancement than symptomatic ones (68% vs. 25%, p < 0.05); their mean signal change was also higher (46% vs. 15%, p < 0.01) and this appeared to correlate with a thicker fibrous cap on histology. Conclusions: Symptomatic patients had more quadrants with signal drop suggesting larger inflammatory infiltrates. Asymptomatic individuals showed significantly more enhancement possibly suggesting greater stability as a result of thicker fibrous caps. However, some asymptomatic plaques also had focal areas of signal drop, suggesting an occult macrophage burden. If validated by larger studies, USPIO may be a useful dual contrast agent able to improve risk stratification of patients with carotid stenosis and inform selection for intervention.

Effect of simulated rock dumping on geotextile

The use of geotextiles in coastal structures such as revetments and bund walls has become a common practice. The performance of these structures during their lifetime depends on the durability of geotextile used. During construction of these coastal structures, geotextiles are subjected to a drop load with high impact stress and that can damage the geotextile. In the current design practice, index tests are insufficient in predicting the performance of the geotextile. This puts the stability and performance of the coastal structures at risk. The current geotextile design guidelines are based on index tests and there is no standard procedure to account for the potential loss in the geotextile’s mechanical properties during installation (construction).This study aims to develop a standard procedure to estimate the properties of geotextile after its installation and using these properties for designing the performance of these structures. This paper describes the laboratory method of simulating large scale rock dumping on non-woven geotextiles and how to quantify the retained strength of damaged geotextiles. Results show that the reduction in retained strength of geotextile could extent up to 26% during installation.

Organosolv pretreatment of plant biomass for enhanced enzymatic saccharification

The combination of dwindling petroleum reserves and population growth make the development of renewable energy and chemical resources more pressing than ever before. Plant biomass is the most abundant renewable source for energy and chemicals. Enzymes can selectively convert the polysaccharides in plant biomass into simple sugars which can then be upgraded to liquid fuels and platform chemicals using biological and/or chemical processes. Pretreatment is essential for efficient enzymatic saccharification of plant biomass and this article provides an overview of how organic solvent (organosolv) pretreatments affect the structure and chemistry of plant biomass, and how these changes enhance enzymatic saccharification. A comparison between organosolv pretreatments utilizing broadly different classes of solvents (i.e., low boiling point, high boiling point, and biphasic) is presented, with a focus on solvent recovery and formation of by-products. The reaction mechanisms that give rise to these by-products are investigated and strategies to minimize by-product formation are suggested. Finally, process simulations of organosolv pretreatments are compared and contrasted, and discussed in the context of an industrial-scale plant biomass to fermentable sugar process.

Effect of position on precision within the recording field of a markerless motion capture system

Introduction Markerless motion capture systems are relatively new devices that can significantly speed up capturing full body motion. A precision of the assessment of the finger’s position with this type of equipment was evaluated at 17.30 ± 9.56 mm when compare to an active marker system [1]. The Microsoft Kinect was proposed to standardized and enhanced clinical evaluation of patients with hemiplegic cerebral palsy [2]. Markerless motion capture systems have the potential to be used in a clinical setting for movement analysis, as well as for large cohort research. However, the precision of such system needs to be characterized. Global objectives • To assess the precision within the recording field of the markerless motion capture system Openstage 2 (Organic Motion, NY). • To compare the markerless motion capture system with an optoelectric motion capture system with active markers. Specific objectives • To assess the noise of a static body at 13 different location within the recording field of the markerless motion capture system. • To assess the smallest oscillation detected by the markerless motion capture system. • To assess the difference between both systems regarding the body joint angle measurement. Methods Equipment • OpenStage® 2 (Organic Motion, NY) o Markerless motion capture system o 16 video cameras (acquisition rate : 60Hz) o Recording zone : 4m * 5m * 2.4m (depth * width * height) o Provide position and angle of 23 different body segments • VisualeyezTM VZ4000 (PhoeniX Technologies Incorporated, BC) o Optoelectric motion capture system with active markers o 4 trackers system (total of 12 cameras) o Accuracy : 0.5~0.7mm Protocol & Analysis • Static noise: o Motion recording of an humanoid mannequin was done in 13 different locations o RMSE was calculated for each segment in each location • Smallest oscillation detected: o Small oscillations were induced to the humanoid mannequin and motion was recorded until it stopped. o Correlation between the displacement of the head recorded by both systems was measured. A corresponding magnitude was also measured. • Body joints angle: o Body motion was recorded simultaneously with both systems (left side only). o 6 participants (3 females; 32.7 ± 9.4 years old) • Tasks: Walk, Squat, Shoulder flexion & abduction, Elbow flexion, Wrist extension, Pronation / supination (not in results), Head flexion & rotation (not in results), Leg rotation (not in results), Trunk rotation (not in results) o Several body joint angles were measured with both systems. o RMSE was calculated between signals of both systems. Results Conclusion Results show that the Organic Motion markerless system has the potential to be used for assessment of clinical motor symptoms or motor performances However, the following points should be considered: • Precision of the Openstage system varied within the recording field. • Precision is not constant between limb segments. • The error seems to be higher close to the range of motion extremities.

Rice husk biochar and crop residue amendment in subtropical cropping soils: Effect on biomass production, nitrogen use efficiency and greenhouse gas emissions

We investigated the effect of maize residues and rice husk biochar on biomass production, fertiliser nitrogen recovery (FNR) and nitrous oxide (N2O) emissions for three different subtropical cropping soils. Maize residues at two rates (0 and 10 t ha−1) combined with three rates (0, 15 and 30 t ha-1) of rice husk biochar were added to three soil types in a pot trial with maize plants. Soil N2O emissions were monitored with static chambers for 91 days. Isotopic 15N-labelled urea was applied to the treatments without added crop residues to measure the FNR. Crop residue incorporation significantly reduced N uptake in all treatments but did not affect overall FNR. Rice husk biochar amendment had no effect on plant growth and N uptake but significantly reduced N2O and carbon dioxide (CO2) emissions in two of the three soils. The incorporation of crop residues had a contrasting effect on soil N2O emissions depending on the mineral N status of the soil. The study shows that effects of crop residues depend on soil properties at the time of application. Adding crop residues with a high C/N ratio to soil can immobilise N in the soil profile and hence reduce N uptake and/or total biomass production. Crop residue incorporation can either stimulate or reduce N2O emissions depending on the mineral N content of the soil. Crop residues pyrolysed to biochar can potentially stabilise native soil C (negative priming) and reduce N2O emissions from cropping soils thus providing climate change mitigation potential beyond the biochar C storage in soils. Incorporation of crop residues as an approach to recycle organic materials and reduce synthetic N fertiliser use in agricultural production requires a thorough evaluation, both in terms of biomass production and greenhouse gas emissions.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Optical and chemical properties of polyterpenol thin films deposited via plasma-enhanced chemical vapor deposition

The development of novel organic polymer thin films is essential for the advancement of many emerging fields including organic electronics and biomedical coatings. In this study, the effect of synthesis conditions, namely radio frequency (rf) deposition power, on the material properties of polyterpenol thin films derived from nonsynthetic environmentally friendly monomer was investigated. At lower deposition powers, the polyterpenol films preserved more of the original monomer constituents, such as hydroxy functional groups; however, they were also softer and more hydrophilic compared to polymers fabricated at higher power. Enhanced monomer fragmentation and consequent reduction in the presence of the polar groups in the structure of the high-power samples reduced their optical band gap value from 2.95 eV for 10 W to 2.64 eV for 100 W. Regardless of deposition power, all samples were found to be optically transparent with smooth, defect-free, and homogenous surfaces.

The effect of polyterpenol thin film surfaces on bacterial viability and adhesion

The nanometer scale surface topography of a solid substrate is known to influence the extent of bacterial attachment and their subsequent proliferation to form biofilms. As an extension of our previous work on the development of a novel organic polymer coating for the prevention of growth of medically significant bacteria on three-dimensional solid surfaces, this study examines the effect of surface coating on the adhesion and proliferation tendencies of Staphylococcus aureus and compares to those previously investigated tendencies of Pseudomonas aeruginosa on similar coatings. Radio frequency plasma enhanced chemical vapor deposition was used to coat the surface of the substrate with thin film of terpinen-4-ol, a constituent of tea-tree oil known to inhibit the growth of a broad range of bacteria. The presence of the coating decreased the substrate surface roughness from approximately 2.1 nm to 0.4 nm. Similar to P. aeruginosa, S. aureus presented notably different patterns of attachment in response to the presence of the surface film, where the amount of attachment, extracellular polymeric substance production, and cell proliferation on the coated surface was found to be greatly reduced compared to that obtained on the unmodified surface. This work suggests that the antimicrobial and antifouling coating used in this study could be effectively integrated into medical and other clinically relevant devices to prevent bacterial growth and to minimize bacteria-associated adverse host responses.

Effect of deletion of Ghrelin-O-Acyltransferase on the pulsatile release of growth hormone in mice

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat−/− mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat−/− mice.

Evaluation of polymeric nanomedicines targeted to PSMA: Effect of ligand on targeting efficiency

Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA−). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.

Caveolin-1 is required for lateral line neuromast and notochord development

Caveolae have been linked to diverse cellular functions and to many disease states. In this study we have used zebrafish to examine the role of caveolin-1 and caveolae during early embryonic development. During development, expression is apparent in a number of tissues including Kupffer's vesicle, tailbud, intersomite boundaries, heart, branchial arches, pronephric ducts and periderm. Particularly strong expression is observed in the sensory organs of the lateral line, the neuromasts and in the notochord where it overlaps with expression of caveolin-3. Morpholino-mediated downregulation of Cav1α caused a dramatic inhibition of neuromast formation. Detailed ultrastructural analysis, including electron tomography of the notochord, revealed that the central regions of the notochord has the highest density of caveolae of any embryonic tissue comparable to the highest density observed in any vertebrate tissue. In addition, Cav1α downregulation caused disruption of the notochord, an effect that was enhanced further by Cav3 knockdown. These results indicate an essential role for caveolin and caveolae in this vital structural and signalling component of the embryo.

The effect of pressure and W-doping on the properties of ZnO thin films for NO2 gas sensing

Pure and W-doped ZnO thin films were obtained using magnetron sputtering at working pressures of 0.4 Pa and 1.33 Pa. The films were deposited on glass and alumina substrates at room temperature and subsequently annealed at 400oC for 1 hour in air. The effects of pressure and W-doping on the structure, chemical, optical and electronic properties of the ZnO films for gas sensing were examined. From AFM, the doped film deposited at higher pressure (1.33 Pa) has spiky morphology with much lower grain density and porosity compared to the doped film deposited at 0.4 Pa. The average gain size and roughness of the annealed films were estimated to be 65 nm and 2.2 nm, respectively with slightly larger grain size and roughness appeared in the doped films. From XPS the films deposited at 1.33 Pa favored the formation of adsorbed oxygen on the film surface and this has been more pronounced in the doped film which created active sites for OH adsorption. As a consequence the W-doped film deposited at 1.33 Pa was found to have lower oxidation state of W (35.1 eV) than the doped film deposited at 0.4 Pa (35.9 eV). Raman spectra indicated that doping modified the properties of the ZnO film and induced free-carrier defects. The transmittance of the samples also reveals an enhanced free-carrier density in the W-doped films. The refractive index of the pure film was also found to increase from 1.7 to 2.2 after W-doping whereas the optical band gap only slightly increased. The W-doped ZnO film deposited at 0.4 Pa appeared to have favorable properties for enhanced gas sensing. This film showed significantly higher sensing performance towards 5-10 ppm NO2 at lower operating temperature of 150oC most dominantly due to increased free-carrier defects achieved by W-doping.