Heterogeneity of miR-10b expression in circulating tumor cells

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as € liquid biopsyto aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch ® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Mobile assessment of on-road air pollution and its sources along the East-West Highway in Bhutan

Human exposures in transportation microenvironments are poorly represented by ambient stationary monitoring. A number of on-road studies using vehicle-based mobile monitoring have been conducted to address this. Most previous studies were conducted on urban roads in developed countries where the primary emission source was vehicles. Few studies have examined on-road pollution in developing countries in urban settings. Currently, no study has been conducted for roadways in rural environments where a substantial proportion of the population live. This study aimed to characterize on-road air quality on the East-West Highway (EWH) in Bhutan and identify its principal sources. We conducted six mobile measurements of PM10, particle number (PN) count and CO along the entire 570 km length of the EWH. We divided the EWH into five segments, R1-R5, taking the road length between two district towns as a single road segment. The pollutant concentrations varied widely along the different road segments, with the highest concentrations for R5 compared with other road segments (PM10 = 149 µg/m3, PN = 5.74 × 104 particles/cm-3, CO = 0.19 ppm), which is the final segment of the road to the capital. Apart from vehicle emissions, the dominant sources were road works, unpaved roads and roadside combustion activities. Overall, the highest contributions above the background levels were made by unpaved roads for PM10 (6 times background), and vehicle emissions for PN and CO (5 and 15 times background, respectively). Notwithstanding the differences in instrumentation used and particle size range measured, the current study showed lower PN concentrations compared with similar on-road studies. However, concentrations were still high enough that commuters, road maintenance workers and residents living along the EWH, were potentially exposed to elevated pollutant concentrations from combustion and non-combustion sources. Future studies should focus on assessing the dispersion patterns of roadway pollutants and defining the short- and long-term health impacts of exposure in Bhutan, as well as in other developing countries with similar characteristics.

Power system stability implications from electromechanical wave propagation

Electromechanical wave propagation characterizes the first-swing dynamic response in a spatially delayed manner. This paper investigates the characteristics of this phenomenon in two-dimensional and one-dimensional power systems. In 2-D systems, the wave front expands as a ripple in a pond. In 1-D systems, the wave front is more concentrated, retains most of its magnitude, and travels like a pulse on a string. This large wave front is more impactful upon any weak link and easily causes transient instability in 1-D systems. The initial disturbance injects both high and low frequency components, but the lumped nature of realistic systems only permits the lower frequency components to propagate through. The kinetic energy split at a junction is equal to the generator inertia ratio in each branch in an idealized continuum system. This prediction is approximately valid in a realistic power system. These insights can enhance understanding and control of the traveling waves.

Fabrication and characterization of plasma polymer thin films from monoterpene alcohols for applications in organic electronics and biotechnology

After more than twenty years of basic and applied research, the use of nanotechnology in the design and manufacture of nanoscale materials is rapidly increasing, particularly in commercial applications that span from electronics across renewable energy areas, and biomedical devices. Novel polymers are attracting significant attention for they promise to provide a low−cost high−performance alternative to existing materials. Furthermore, these polymers have the potential to overcome limitations imposed by currently available materials thus enabling the development of new technologies and applications that are currently beyond our reach. This work focuses on the development of a range of new low−cost environmentally−friendly polymer materials for applications in areas of organic (flexible) electronics, optics, and biomaterials. The choice of the monomer reflects the environmentally−conscious focus of this project. Terpinen−4−ol is a major constituent of Australian grown Melaleuca alternifolia (tea tree) oil, attributed with the oil's antimicrobial and anti−inflammatory properties. Plasma polymerisation was chosen as a deposition technique for it requires minimal use of harmful chemicals and produces no hazardous by−products. Polymer thin films were fabricated under varied process conditions to attain materials with distinct physico−chemical, optoelectrical, biological and degradation characteristics. The resultant materials, named polyterpenol, were extensively characterised using a number of well−accepted and novel techniques, and their fundamental properties were defined. Polyterpenol films were demonstrated to be hydrocarbon rich, with variable content of oxygen moieties, primarily in the form of hydroxyl and carboxyl functionalities. The level of preservation of original monomer functionality was shown to be strongly dependent on the deposition energy, with higher applied power increasing the molecular fragmentation and substrate temperature. Polyterpenol water contact angle contact angle increased from 62.7° for the 10 W samples to 76.3° for the films deposited at 100 W. Polymers were determined to resist solubilisation by water, due to the extensive intermolecular and intramolecular hydrogen bonds present, and other solvents commonly employed in electronics and biomedical processing. Independent of deposition power, the surface topography of the polymers was shown to be smooth (Rq <0.5 nm), uniform and defect free. Hardness of polyterpenol coatings increased from 0.33 GPa for 10 W to 0.51 GPa for 100 W (at 500 μN load). Coatings deposited at higher input RF powers showed less mechanical deformation during nanoscratch testing, with no considerable damage, cracking or delamination observed. Independent of the substrate, the quality of film adhesion improved with RF power, suggesting these coatings are likely to be more stable and less susceptible to wear. Independent of fabrication conditions, polyterpenol thin films were optically transparent, with refractive index approximating that of glass. Refractive index increased slightly with deposition power, from 1.54 (10 W) to 1.56 (100 W) at 500 nm. The optical band gap values declined with increasing power, from 2.95 eV to 2.64 eV, placing the material within the range for semiconductors. Introduction of iodine impurity reduced the band gap of polyterpenol, from 2.8 eV to 1.64 eV, by extending the density of states more into the visible region of the electromagnetic spectrum. Doping decreased the transparency and increased the refractive index from 1.54 to 1.70 (at 500 nm). At optical frequencies, the real part of permittivity (k) was determined to be between 2.34 and 2.65, indicating a potential low-k material. These permittivity values were confirmed at microwave frequencies, where permittivity increased with input RF energy – from 2.32 to 2.53 (at 10 GHz ) and from 2.65 to 2.83 (at 20 GHz). At low frequencies, the dielectric constant was determined from current−voltage characteristics of Al−polyterpenol−Al devices. At frequencies below 100 kHz, the dielectric constant varied with RF power, from 3.86 to 4.42 at 1 kHz. For all samples, the resistivity was in order of 10⁸−10⁹ _m (at 6 V), confirming the insulating nature of polyterpenol material. In situ iodine doping was demonstrated to increase the conductivity of polyterpenol, from 5.05 × 10⁻⁸ S/cm to 1.20 × 10⁻⁶ S/cm (at 20 V). Exposed to ambient conditions over extended period of time, polyterpenol thin films were demonstrated to be optically, physically and chemically stable. The bulk of ageing occurred within first 150 h after deposition and was attributed to oxidation and volumetric relaxation. Thermal ageing studies indicated thermal stability increased for the films manufactured at higher RF powers, with degradation onset temperature associated with weight loss shifting from 150 ºC to 205 ºC for 10 W and 100 W polyterpenol, respectively. Annealing the films to 405 °C resulted in full dissociation of the polymer, with minimal residue. Given the outcomes of the fundamental characterisation, a number of potential applications for polyterpenol have been identified. Flexibility, tunable permittivity and loss tangent properties of polyterpenol suggest the material can be used as an insulating layer in plastic electronics. Implementation of polyterpenol as a surface modification of the gate insulator in pentacene-based Field Effect Transistor resulted in significant improvements, shifting the threshold voltage from + 20 V to –3 V, enhancing the effective mobility from 0.012 to 0.021 cm²/Vs, and improving the switching property of the device from 10⁷ to 10⁴. Polyterpenol was demonstrated to have a hole transport electron blocking property, with potential applications in many organic devices, such as organic light emitting diodes. Encapsulation of biomedical devices is also proposed, given that under favourable conditions, the original chemical and biological functionality of terpinen−4−ol molecule can be preserved. Films deposited at low RF power were shown to successfully prevent adhesion and retention of several important human pathogens, including P. aeruginosa, S. aureus, and S. epidermidis, whereas films deposited at higher RF power promoted bacterial cell adhesion and biofilm formation. Preliminary investigations into in vitro biocompatibility of polyterpenol demonstrated the coating to be non−toxic for several types of eukaryotic cells, including Balb/c mice macrophage and human monocyte type (HTP−1 non-adherent) cells. Applied to magnesium substrates, polyterpenol encapsulating layer significantly slowed down in vitro biodegradation of the metal, thus increasing the viability and growth of HTP−1 cells. Recently, applied to varied nanostructured titanium surfaces, polyterpenol thin films successfully reduced attachment, growth, and viability of P. aeruginosa and S. aureus.

Experimental investigation of the effects of oxygenated fuels on exhaust emissions in a heavy duty diesel engine

Physical and chemical properties of biofuels vary among various feedstocks and their subsequent conversions to fuels. The biofuels contain various amounts of oxygen, and this has a significant influence on exhaust emission. This oxygen content has been considered in order to investigate its effect on diesel engine exhaust emissions. The experiments have been conducted with a heavy duty diesel engine and various oxygenated fuels. It is found that the amount of oxygen in the fuel has a high level of influence on its exhaust emissions, and this provides agreement with diesel emissions results such as PN reduction. By increasing the amount of oxygen in the blend (by adding more biofuel), the particulate number (PN) is reduced and NOx increases gradually. However, the variation of PN and NOx are not similar for waste cooking biodiesel (WCBD) and butanol blend, even though their oxygen content are the same in the blends. This is due to the source of the biofuel and their internal chemistry.

Development of type I genetic markers from expressed sequence tags in highly polymorphic species

Expressed sequence tag (EST) databases provide a primary source of nuclear DNA sequences for genetic marker development in non-model organisms. To date, the process has been relatively inefficient for several reasons: - 1) priming site polymorphism in the template leads to inferior or erratic amplification; - 2) introns in the target amplicon are too large and/or numerous to allow effective amplification under standard screening conditions, and; - 3) at least occasionally, a PCR primer straddles an exon–intron junction and is unable to bind to genomic DNA template. The first is only a minor issue for species or strains with low heterozygosity but becomes a significant problem for species with high genomic variation, such as marine organisms with extremely large effective population sizes. Problems arising from unanticipated introns are unavoidable but are most pronounced in intron-rich species, such as vertebrates and lophotrochozoans. We present an approach to marker development in the Pacific oyster Crassostrea gigas, a highly polymorphic and intron-rich species, which minimizes these problems, and should be applicable to other non-model species for which EST databases are available. Placement of PCR primers in the 3′ end of coding sequence and 3′ UTR improved PCR success rate from 51% to 97%. Almost all (37 of 39) markers developed for the Pacific oyster were polymorphic in a small test panel of wild and domesticated oysters.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) and its interactions with glycosaminoglycans: 2. Biochemical analyses

Platelet endothelial cell adhesion molecule 1 (PECAM-1) (CD31), a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules with six Ig-like domains, has a range of functions, notably its contributions to leukocyte extravasation during inflammation and in maintaining vascular endothelial integrity. Although PECAM-1 is known to mediate cell adhesion by homophilic binding via domain 1, a number of PECAM-1 heterophilic ligands have been proposed. Here, the possibility that heparin and heparan sulfate (HS) are ligands for PECAM-1 was reinvestigated. The extracellular domain of PECAM-1 was expressed first as a fusion protein with the Fc region of human IgG1 fused to domain 6 and second with an N-terminal Flag tag on domain 1 (Flag-PECAM-1). Both proteins bound heparin immobilized on a biosensor chip in surface plasmon resonance (SPR) binding experiments. Binding was pH-sensitive but is easily measured at slightly acidic pH. A series of PECAM-1 domain deletions, prepared in both expression systems, were tested for heparin binding. This revealed that the main heparin-binding site required both domains 2 and 3. Flag-PECAM-1 and a Flag protein containing domains 1-3 bound HS on melanoma cell surfaces, but a Flag protein containing domains 1-2 did not. Heparin oligosaccharides inhibited Flag-PECAM-1 from binding immobilized heparin, with certain structures having greater inhibitory activity than others. Molecular modeling similarly identified the junction of domains 2 and 3 as the heparin-binding site and further revealed the importance of the iduronic acid conformation for binding. PECAM-1 does bind heparin/HS but by a site that is distinct from that required for homophilic binding.

Reducing luminance contrast on the window wall and users’ interventions in an office room

High luminance contrast between windows and surrounding surfaces could cause discomfort glare, which could reduce office workers’ productivity. It might also increase energy usage of buildings due to occupants’ interventions in lighting conditions to improve indoor visual quality. It is presumed that increasing the luminance of the areas surrounding the windows using a supplementary system, such Light Emitting Diodes (LEDs), could reduce discomfort glare. This paper reports on the results of a pilot study in a conventional office in Brisbane, Australia. The outcomes of this study indicated that a supplementary LED system could reduce the luminance contrast on the window wall from values in the order of 24:1 to 12:1. The results suggest that this reduction could significantly reduce discomfort glare from windows, as well as diminishing the likelihood of users’ intention to turn on the ceiling lights and/ or to move the blind down.

Prevalence of foot disease and risk factors in general inpatient populations: A systematic review and meta-analysis

Objective: To systematically review studies reporting the prevalence in general adult inpatient populations of foot disease disorders (foot wounds, foot infections, collective ‘foot disease’) and risk factors (peripheral arterial disease (PAD), peripheral neuropathy (PN), foot deformity). Methods: A systematic review of studies published between 1980 and 2013 was undertaken using electronic databases (MEDLINE, EMBASE and CINAHL). Keywords and synonyms relating to prevalence, inpatients, foot disease disorders and risk factors were used. Studies reporting foot disease or risk factor prevalence data in general inpatient populations were included. Included study's reference lists and citations were searched and experts consulted to identify additional relevant studies. 2 authors, blinded to each other, assessed the methodological quality of included studies. Applicable data were extracted by 1 author and checked by a second author. Prevalence proportions and SEs were calculated for all included studies. Pooled prevalence estimates were calculated using random-effects models where 3 eligible studies were available. Results: Of the 4972 studies initially identified, 78 studies reporting 84 different cohorts (total 60 231 517 participants) were included. Foot disease prevalence included: foot wounds 0.01–13.5% (70 cohorts), foot infections 0.05–6.4% (7 cohorts), collective foot disease 0.2–11.9% (12 cohorts). Risk factor prevalence included: PAD 0.01–36.0% (10 cohorts), PN 0.003–2.8% (6 cohorts), foot deformity was not reported. Pooled prevalence estimates were only able to be calculated for pressure ulcer-related foot wounds 4.6% (95% CI 3.7% to 5.4%)), diabetes-related foot wounds 2.4% (1.5% to 3.4%), diabetes-related foot infections 3.4% (0.2% to 6.5%), diabetes-related foot disease 4.7% (0.3% to 9.2%). Heterogeneity was high in all pooled estimates (I2=94.2–97.8%, p<0.001). Conclusions: This review found high heterogeneity, yet suggests foot disease was present in 1 in every 20 inpatients and a major risk factor in 1 in 3 inpatients. These findings are likely an underestimate and more robust studies are required to provide more precise estimates.

How many inpatients in our hospitals have foot complications? The foot disease in inpatients study

Background Foot complications have been found to affect large proportions of hospital in patients with diabetes. However, no studies have investigated the proportion of foot complications affecting all people in general inpatient populations. The aims of this cross-sectional study were to investigate the point-prevalence of different foot complications in general inpatient populations, analyse differences in diabetes and non-diabetes sub-groups, and examine characteristics of people primarily admitted for a foot complication. Methods Eligible participants were all adults admitted overnight, for any reason, into five diverse hospitals on one day; excluding maternity, mental health and cognitively impaired patients. All participants underwent a physical foot examination, by trained podiatrists using validated measures, to clinically diagnose different foot complications; including foot wounds, infections, deformity, peripheral arterial disease (PAD) and peripheral neuropathy (PN). Data were also collected on participants' primary reason for admission and a range of demographic, social determinant, medical history, foot complication history, self-care and footwear risk factors. Results Overall, 733 participants consented (83% of eligible participants); mean(±SD) age 62(±19) years, 480 (55.8%) male and 172 (23.5%) had diabetes. Foot complication prevalence included: wounds 9.0% (95% CI) (5.1-8.7), infections 3.3% (2.2-4.9), deformity 22.4% (19.5-26.7), PAD 21.0% (18.2-24.1) and PN 22.0% (19.1-25.1). Diabetes populations had significantly more foot complications than non-diabetes (p < 0.01); wounds (15.7% vs 7.0%), infections (7.1% vs 2.2%), deformity (30.5% vs 19.9%), PAD (35.1% vs 16.7%) and PN (43.3% vs 15.4%). Foot complications were the primary reason for admission in 7.4% (95% CI) (5.7-9.5) of all participants. In a backwards stepwise multivariate analysis having a foot complication as the primary reason for admission was independently associated (OR (95% CI) with foot wounds (18.9 (7.3-48.7)), foot infections (6.0 (1.6-22.4)), history of amputation (4.7 (1.3-17.0) and PAD (2.9 (1.3-6.6)). Conclusions Findings of this study indicate one in every ten hospital inpatients had an active foot wound or infection. In patients with diabetes had significantly higher proportions of foot complications than non-diabetes inpatients. Remarkably one in every thirteen inpatients in this study were primarily hospitalised for a foot complication. Further research and policy is required to tackle this seemingly large inpatient foot complication burden.

Highly efficient spin-conversion effect leading to energy up-converted electroluminescence in singlet fission photovoltaics

Free charge generation in donor-acceptor (D-A) based organic photovoltaic diodes (OPV) progresses through formation of charge-transfer (CT) and charge-separated (CS) states and excitation decay to the triplet level is considered as a terminal loss. On the other hand a direct excitation decay to the triplet state is beneficial for multiexciton harvesting in singlet fission photovoltaics (SF-PV) and the formation of CT-state is considered as a limiting factor for multiple triplet harvesting. These two extremes when present in a D-A system are expected to provide important insights into the mechanism of free charge generation and spin-character of bimolecular recombination in OPVs. Herein, we present the complete cycle of events linked to spin conversion in the model OPV system of rubrene/C60. By tracking the spectral evolution of photocurrent generation at short-circuit and close to open-circuit conditions we are able to capture spectral changes to photocurrent that reveal the triplet character of CT-state. Furthermore, we unveil an energy up-conversion effect that sets in as a consequence of triplet population build-up where triplet-triplet annihilation (TTA) process effectively regenerates the singlet excitation. This detailed balance is shown to enable a rare event of photon emission just above the open-circuit voltage (VOC) in OPVs.

HER2 positive gastric and gastroesophageal adenocarcinoma; An Irish tertiary center experience

Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2) over expression and gene amplification metastatic gastric cancer. Here we present the prevalence of HER2 positive gastric cancer in an Irish population, the use of Trastuzumab in first line and beyond progression. Methods: The study was conducted in St James's Hospital, Dublin. A retrospective analysis of the date of patients with HER2 positive gastric cancer over a period of 3 years was carried out. Her2 positive was defined as immunohistochemistry (IHC) score of +3, of IHC score of +2 and increased gene copy number by fluorescence in situ hybridization (FISH). Overall survival was calculated from the day of initiation of treatment with Trastuzumab until death. Results: During the study period 140 patients with gastric and gastro-esophageal junction adenocarcinoma were treated. Out of those, 30 (21.4%) had HER2 positive disease. Among HER2 positive disease patients 18 (12.8%) were treated with first line Trastuzumab containing regimen with a median overall survival of 13 months. Nine (50%) developed progressive disease while on Trastuzumab and of those, 4 (22.2%) patients continued on Trastuzumab beyond progression, two (11.1%) of whom achieved stable disease and a prolonged survival. Conclusion: HER2 positivity rate in an Irish population with advanced gastric and gastro-esophageal junction adenocarcinoma is 21.4%. Treatment with Trastuzumab in the first line in combination with chemotherapy is a reasonable approach. Continuation of Trastuzumab beyond progression is a feasible strategy that requires further exploration.

Switchable-feed reconfigurable ultra-wide band planar antenna

Reconfigurable antennas capable of radiating in only specific desired directions increase system functionality in applications like direction finding and beam steering. This paper presents the design simulation, fabrication and measurement of a horizontally polarized, direction reconfigurable Vivaldi antenna, designed for the lower-band UWB (2-6 GHz). This design employs eight circularly distributed independent Vivaldi antennas with a common port, electronically controlled by PIN diodes acting as RF switches. Experimental results show that the reconfigurable antenna has a bandwidth of 4 GHz (2-6 GHz), with 5 dB gain in the desired direction and capable of steering over the 360° range.

Electronically-reconfigurable horizontally polarized wide-band planar antenna

Antennas are a necessary and critical component of communications and radar systems, but their inability to adjust to new operating scenarios can sometimes limit the system performance. Reconfigurable antennas capable of radiating in only specific desired directions can ameliorate these restrictions and help to achieve increased functionality in applications like direction finding and beam steering. This paper presents the design simulation, fabrication and measurement of a wide-band, horizontally polarized, direction reconfigurable microstrip antenna operating at 2.45 GHz. The design employs a central horizontally polarized omnidirectional active element surrounded by electronically reconfigurable parasitic microstrip elements, controlled by PIN diodes acting as RF switches. Experimental results show that the reconfigurable antenna has a bandwidth of 40% (2-3 GHz), with 3 dB gain in the desired direction and capable of steering over the 360° range.