The Role of K+ and Cl- Channels in the Regulation of Retinal Arteriolar Tone and Blood Flow

Purpose: This study tested the role of K(+)- and Cl(-)-channels in retinal arteriolar smooth muscle in the regulation of retinal blood flow.

Methods: Studies were carried out in adult Male Hooded Lister rats. Selectivity of ion channel blockers was established using electrophysiological recordings from smooth muscle in isolated arterioles under voltage clamp conditions. Leukocyte velocity and retinal arteriolar diameters were measured in anesthetised animals using leukocyte fluorography and fluorescein angiography imaging with a confocal scanning laser ophthalmoscope. These values were used to estimate volumetric flow, which was compared between control conditions and following intravitreal injections of ion channel blockers, either alone or in combination with the vasoconstrictor potent Endothelin 1 (Et1).

Results: Voltage activated K(+)-current (IKv) was inhibited by correolide, large conductance (BK) Ca(2+)-activated K(+)-current (IKCa) by Penitrem A, and Ca(2+)-activated Cl(-)-current (IClCa) by disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). Intravitreal injections (10µl) of DIDS (estimated intraocular concentration 10mM) increased flow by 22%, whereas the BK-blockers Penitrem A (1µM) and iberiotoxin (4µM), and the IKv-inhibitor correolide (40µM) all decreased resting flow by approximately 10%. Et1 (104nM) reduced flow by almost 65%. This effect was completely reversed by DIDS but was unaffected by Penitrem A, iberiotoxin or correolide.

Conclusions: These results suggest that Cl(-)-channels in retinal arteriolar smooth muscle limit resting blood flow and play an obligatory role in Et1 responses. K(+)-channel activity promotes basal flow but exerts little modifying effect on the Et1 response. Cl(-)-channels may be appropriate molecular targets in retinal pathologies characterised by increased Et1 activity and reduced blood flow.

Defining target volumes for stereotactic ablative radiotherapy of early-stage lung tumours: a comparison of three-dimensional 18F-fluorodeoxyglucose positron emission tomography and four-dimensional computed tomography.:PETCT versus 4DCT for SABR in Early Stage NSCLC

AIMS: High local control rates are achieved in stage I lung cancer using
stereotactic ablative radiotherapy. Target delineation is commonly based on
four-dimensional computed tomography (CT) scans. Target volumes defined by
positron emission tomography/computed tomography (PET/CT) are compared with those defined by four-dimensional CT and conventional ('three-dimensional')
(18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT.

MATERIALS AND METHODS: For 16 stage I non-small cell lung cancer tumours, six
approaches for deriving PET target volumes were evaluated: manual contouring,
standardised uptake value (SUV) absolute threshold of 2.5, 35% of maximum SUV
(35%SUV(MAX)), 41% of SUV(MAX) (41%SUV(MAX)) and two different source to
background ratio techniques (SBR-1 and SBR-2). PET-derived target volumes were compared with the internal target volume (ITV) from the modified maximum
intensity projection (MIP(MOD) ITV). Volumetric and positional correlation was
assessed using the Dice similarity coefficient (DSC).

RESULTS: PET-based target volumes did not correspond to four-dimensional CT-based target volumes. The mean DSC relative to MIP(MOD) ITV were: PET manual = 0.64, SUV2.5 = 0.64, 35%SUV(MAX) = 0.63, 41%SUV(MAX) = 0.57. SBR-1 = 0.52, SBR-2 =0.49. PET-based target volumes were smaller than corresponding MIP ITVs.

CONCLUSIONS: Conventional three-dimensional (18)F-FDG PET-derived target volumes for lung stereotactic ablative radiotherapy did not correspond well with those derived from four-dimensional CT, including those in routine clinical use
(MIP(MOD) ITV). Caution is required in using three-dimensional PET for motion
encompassing target volume delineation.

Idealized Operation of Third-Harmonic-Peaking Class-Ef Power Amplifier with Extended Maximum Operating Frequency

A new variant of Class-EF power amplifier (PA), the so-called third-harmonic-peaking Class-EF, is presented. It inherits a soft-switching operation from the Class-E PA and a low peak switch voltage from the Class-F PA. More importantly, the new topology allows operations at higher frequencies and permits deployment of large transistors which is normally prohibited since they are always accompanied with high output capacitances. Using a simple transmission-line load network, the PA is synthesized to satisfy Class-EF impedances at fundamental frequency, third harmonic, and all even harmonics as well as to simultaneously provide an impedance matching to 50-Ω load.

Conductivity/activation energy relationships for cement-based materials undergoing cyclic thermal excursions

The electrical conductivity of a range of concrete mixes, with and without supplementary cementitious materials (SCM), is studied through multiple cycles of heating and cooling over the extended temperature range −30/+70 °C. When presented in an Arrhenius format, the experimental results display hysteresis effects at the low-temperature end of the thermal cycle and, in those concretes containing supplementary cementitious materials at higher water/binder ratios, hysteresis effects were evident over the entire temperature range becoming more discernible with increasing number of thermal cycles. The depression in both the freezing and thawing point could be clearly identified and was used to estimate pore-neck and pore-cavity radii. A simplified approach is presented to evaluate the volumetric ratio of frozen pore water in terms of conductivity measurements. The results also show that the conductivity and activation energy of the concrete specimens were related to the water/binder ratio, type of SCM, physical state of the pore water and the thermal cycling regime.

Conventional in vivo irradiation procedures are insufficient to accurately determine tumor responses to non-uniform radiation fields

Purpose: To determine differences in overall tumor responses measured by volumetric assessment and bioluminescence imaging (BLI) following exposure to uniform and non-uniform radiation fields in an ectopic prostate tumor model.

Materials and methods: Bioluminescent human prostate tumor xenografts were established by subcutaneous implantation into male mice. Tumors were irradiated with uniform or non-uniform field configurations using conventional in vivo irradiation procedures performed using a 225 kVp generator with custom lead shielding. Tumor responses were measured using Vernier calipers and by BLI using an in vivo imaging system. Survival was defined as the time to quadroupling of pre-treatment tumor volume. 

Results: The correlation between BLI and tumor volume measurements was found to be different for un-irradiated (R = 0.61), uniformly irradiated (R = 0.34) and partially irradiated (R = 0.30) tumors. Uniformly irradiated tumors resulted in an average tumor growth delay of 60 days with median survival of 75 days, compared to partially irradiated tumors which showed an average growth delay of 24 days and median survival of 38 days. 

Conclusions: Correlation between BLI and tumor volume measurements is lower for partially irradiated tumors than those exposed to uniform dose distributions. The response of partially irradiated tumors suggests non-uniformity in response beyond physical dose distribution within the target volume. Dosimetric uncertainty associated with conventional in vivo irradiation procedures prohibits their ability to accurately determine tumor response to non-uniform radiation fields and stresses the need for image guided small animal radiation research platforms.

Wetting of compacted clays under laterally restrained conditions: Initial state, overburden pressure and mineralogy

Compacted clay fills are generally placed at the optimum value of water content and, immediately after placement, they are unsaturated. Wetting might subsequently occur due, for example, to rainfall infiltration, which can cause volumetric deformation of the fill (either swell or collapse) with associated loss of shear strength and structural integrity. If swelling takes place under partially restrained deformation, due for example to the presence of a buried rigid structure or a retaining wall, additional stresses will develop in the soil and these can be detrimental to the stability of walling elements and other building assets. Factors such as dry density, overburden pressure, compaction water content and type of clay are known to influence the development of stresses. This paper investigates these factors by means of an advanced stress path testing programme performed on four different clays with different mineralogy, index properties and geological histories. Specimens of kaolin clay, London Clay, Belfast Clay and Ampthill Clay were prepared at different initial states and subjected to ‘controlled’ wetting, whereby the suction was reduced gradually to zero under laterally restrainedconditions (i.e. K0 conditions). The results showed that the magnitude of the increase in horizontal stresses (and therefore the increase of K0) is influenced by the overburden pressure, compaction water content, dry density at the time of compaction and mineralogy.

On the Performances of Ionic Liquid-Based Electrolytes for Li-NMC Batteries

Herein, the N-butyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide and the N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide room temperature ionic liquids, combined with the lithium bis(trifluoromethanesulfonyl)amide salt, are investigated as electrolytes for Li/LiNi1/3Mn1/3Co1/3O2 (Li/NMC) batteries. To conduct this study, volumetric properties, ionic conductivity and viscosity of the pure ionic liquids and selected electrolytes were firstly determined as a function of temperature and composition in solution. These data were then compared with those measured in the case of the standard alkyl carbonate-based electrolyte: e.g. the EC/PC/3DMC + 1 mol·L−1 LiPF6. The compatibility of the selected electrolytes with the lithium electrode was then investigated by following the evolution of Li/electrolyte interfaces through impedance measurements. Interestingly, the impedances of the investigated Li/electrolyte interfaces were found to be more than three times lower than that measured using the standard electrolyte. Finally, electrochemical performances of the ionic liquid-based electrolytes were investigated using galvanostatic charge and discharge and cyclic voltammetry of each Li/NMC cell. Using these electrolytes, each tested Li cell reaches up to 145 mA·h·g−1 at C/10 and 110 mA·h·g−1 at C with a coulombic efficiency close to 100 %.

STARTEC: Novel processing technologies in the development of a decision support tool to ensure safe and nutritious Ready-To-Eat foods

Ready-to-eat (RTE) foods can be readily consumed with minimum or without any further preparation; their processing is complex—involving thorough decontamination processes— due to their composition of mixed ingredients. Compared with conventional preservation technologies, novel processing technologies can enhance the safety and quality of these complex products by reducing the risk of pathogens and/ or by preserving related health-promoting compounds. These novel technologies can be divided into two categories: thermal and non-thermal. As a non-thermal treatment, High Pressure Processing is a very promising novel methodology that can be used even in the already packaged RTE foods. A new “volumetric” microwave heating technology is an interesting cooking and decontamination method directly applied to foods. Cold Plasma technology is a potential substitute of chlorine washing in fresh vegetable decontamination. Ohmic heating is a heating method applicable to viscous products but also to meat products. Producers of RTE foods have to deal with challenging decisions starting from the ingredients suppliers to the distribution chain. They have to take into account not only the cost factor but also the benefits and food products’ safety and quality. Novel processing technologies can be a valuable yet large investment for several SME food manufacturers, but they need support data to be able to make adequate decisions. Within the FP7 Cooperation funded by the European Commission, the STARTEC project aims to develop an IT decision supporting tool to help food business operators in their risk assessment and future decision making when producing RTE foods with or without novel preservation technologies.

Beam profiles of proton and carbon ions in the relativistic transparency regime

Ion acceleration from relativistic laser solid interactions has been of particular interest over the last decade. While beam profiles have been studied for target normal sheath acceleration (TNSA), such profiles have yet to be described for other mechanisms. Here, experimental data is presented, investigating ion beam profiles from acceleration governed by relativistic transparent laser plasma interaction. The beam shape of carbon C6+ ions and protons has been measured simultaneously with a wide angle spectrometer. It was found that ion beams deviate from the typical Gaussian-like shape found with TNSA and that the profile is governed by electron dynamics in the volumetric laser-plasma interaction with a relativistically transparent plasma; due to the ponderomotive force electrons are depleted from the center of the laser axis and form lobes affecting the ion beam structure. The results are in good agreement with high resolution three-dimensional-VPIC simulations and can be used as a new tool to experimentally distinguish between different acceleration mechanisms.

Rapidly Evolving and Luminous Transients from Pan-STARRS1

In the past decade, several rapidly evolving transients have been discovered whose timescales and luminosities are not easily explained by traditional supernovae (SNe) models. The sample size of these objects has remained small due, at least in part, to the challenges of detecting short timescale transients with traditional survey cadences. Here we present the results from a search within the Pan-STARRS1 Medium Deep Survey (PS1-MDS) for rapidly evolving and luminous transients. We identify 10 new transients with a time above half-maximum (t_1/2) of less than 12 days and -16.5 > M > -20 mag. This increases the number of known events in this region of SN phase space by roughly a factor of three. The median redshift of the PS1-MDS sample is z = 0.275 and they all exploded in star-forming galaxies. In general, the transients possess faster rise than decline timescale and blue colors at maximum light (g_P1-rP1 ≲ -0.2). Best-fit blackbodies reveal photospheric temperatures/radii that expand/cool with time and explosion spectra taken near maximum light are dominated by a blue continuum, consistent with a hot, optically thick, ejecta. We find it difficult to reconcile the short timescale, high peak luminosity (L > 10⁴³erg s^-1), and lack of UV line blanketing observed in many of these transients with an explosion powered mainly by the radioactive decay of ⁵⁶Ni. Rather, we find that many are consistent with either (1) cooling envelope emission from the explosion of a star with a low-mass extended envelope that ejected very little (<0.03 M) radioactive material, or (2) a shock breakout within a dense, optically thick, wind surrounding the progenitor star. After calculating the detection efficiency for objects with rapid timescales in the PS1-MDS we find a volumetric rate of 4800-8000 events yr^-1Gpc^-3(4%-7% of the core-collapse SN rate at z = 0.2).

Binaural Reproduction of Finite Difference Simulations Using Spherical Array Processing

Due to its efficiency and simplicity, the finite-difference time-domain method is becoming a popular choice for solving wideband, transient problems in various fields of acoustics. So far, the issue of extracting a binaural response from finite difference simulations has only been discussed in the context of embedding a listener geometry in the grid. In this paper, we propose and study a method for binaural response rendering based on a spatial decomposition of the sound field. The finite difference grid is locally sampled using a volumetric array of receivers, from which a plane wave density function is computed and integrated with free-field head related transfer functions, in the spherical harmonics domain. The volumetric array is studied in terms of numerical robustness and spatial aliasing. Analytic formulas that predict the performance of the array are developed, facilitating spatial resolution analysis and numerical binaural response analysis for a number of finite difference schemes. Particular emphasis is placed on the effects of numerical dispersion on array processing and on the resulting binaural responses. Our method is compared to a binaural simulation based on the image method. Results indicate good spatial and temporal agreement between the two methods.

The role of complexity metrics in a multi-institutional dosimetry audit of VMAT

OBJECTIVE: To demonstrate the benefit of complexity metrics such as the modulation complexity score (MCS) and monitor units (MUs) in multi-institutional audits of volumetric-modulated arc therapy (VMAT) delivery.

METHODS: 39 VMAT treatment plans were analysed using MCS and MU. A virtual phantom planning exercise was planned and independently measured using the PTW Octavius(®) phantom and seven29(®) 2D array (PTW-Freiburg GmbH, Freiburg, Germany). MCS and MU were compared with the median gamma index pass rates (2%/2 and 3%/3 mm) and plan quality. The treatment planning systems (TPS) were grouped by VMAT modelling being specifically designed for the linear accelerator manufacturer's own treatment delivery system (Type 1) or independent of vendor for VMAT delivery (Type 2). Differences in plan complexity (MCS and MU) between TPS types were compared.

RESULTS: For Varian(®) linear accelerators (Varian(®) Medical Systems, Inc., Palo Alto, CA), MCS and MU were significantly correlated with gamma pass rates. Type 2 TPS created poorer quality, more complex plans with significantly higher MUs and MCS than Type 1 TPS. Plan quality was significantly correlated with MU for Type 2 plans. A statistically significant correlation was observed between MU and MCS for all plans (R = -0.84, p < 0.01).

CONCLUSION: MU and MCS have a role in assessing plan complexity in audits along with plan quality metrics. Plan complexity metrics give some indication of plan deliverability but should be analysed with plan quality.

ADVANCES IN KNOWLEDGE: Complexity metrics were investigated for a national rotational audit involving 34 institutions and they showed value. The metrics found that more complex plans were created for planning systems which were independent of vendor for VMAT delivery.

Industrial scale microwave processing of tomato juice using a novel continuous microwave system

This study evaluated the effect of an industrial scale continuous flow microwave volumetric heating system in comparison to conventional commercial scale pasteurisation for the processing of tomato juice in terms of physicochemical properties, microbial characteristics and antioxidant capacity. The effect against oxidative stress in Caco-2 cells, after in vitro digestion was also investigated. Physicochemical and colour characteristics of juices were very similar between technologies and during storage. Both conventional and microwave pasteurisation inactivated microorganisms and kept them in low levels throughout storage. ABTS⁺ values, but not ORAC, were higher for the microwave pasteurised juice at day 0 however no significant differences between juices were observed during storage. Juice processed with the microwave system showed an increased cytoprotective effect against H₂O₂ induced oxidation in Caco-2 cells. Organoleptic analysis revealed that the two tomato juices were very similar. The continuous microwave volumetric heating system appears to be a viable alternative to conventional pasteurisation.

Characterisation of a two-dimensional liquid-filled ion chamber detector array using flattened and unflattened beams for small fields, small MUs and high dose-rates

In this study, the PTW 1000SRS array with Octavius 4D phantom was characterised for FF and FFF beams. MU linearity, field size, dose rate, dose per pulse (DPP) response and dynamic conformal arc treatment accuracy of the 1000SRS array were assessed for 6MV, 6FFF and 10FFF beams using a Varian TrueBeam STx linac. The measurements were compared with a pinpoint IC, microdiamond IC and EBT3 Gafchromic film. Measured dose profiles and FWHMs were compared with film measurements. Verification of FFF volumetric modulated arc therapy (VMAT) clinical plans were assessed using gamma analysis with 3%/3 mm and 2%/2 mm tolerances (10% threshold). To assess the effect of cross calibration dose rate, clinical plans with different dose rates were delivered and analysed. Output factors agreed with film measurements to within 4.5% for fields between 0.5 and 1 cm and within 2.7% for field sizes between 1.5 and 10 cm and were highly correlated with the microdiamond IC detector. Field sizes measured with the 1000SRS array were within 0.5 mm of film measurements. A drop in response of up to 1.8%, 2.4% and 5.2% for 6MV, 6FFF and 10FFF beams respectively was observed with increasing nominal dose rate. With an increase in DPP, a drop of up to 1.7%, 2.4% and 4.2% was observed in 6MV, 6FFF and 10FFF respectively. The differences in dose following dynamic conformal arc deliveries were less than 1% (all energies) from calculated. Delivered VMAT plans showed an average pass percentage of 99.5(±0.8)% and 98.4(±3.4)% with 2%/2 mm criteria for 6FFF and 10FFF respectively. A drop to 97.7(±2.2)% and 88.4(±9.6)% were observed for 6FFF and 10FFF respectively when plans were delivered at the minimum dose rate and calibrated at the maximum dose rate. Calibration using a beam with the average dose rate of the plan may be an efficient method to overcome the dose rate effects observed by the 1000SRS array.

Long-term changes in oxygen depletion in a small temperate lake: effects of climate change and eutrophication

1. We analysed 41 years of data (1968–2008) from Blelham Tarn, U.K., to determine the consequences of eutrophication and climate warming on hypolimnetic dissolved oxygen (DO).
2. The establishment of thermal stratification was strongly related to the onset of DO depletion in the lower hypolimnion. As a result of a progressively earlier onset of stratification and later overturn, the duration of stratification increased by 38 ± 8 days over the 41 years.
3. The observed rate of volumetric hypolimnetic oxygen depletion (VHODobs) ranged from 0.131 to 0.252 g O2 m−3 per day and decreased significantly over the study period, despite the increase in the mean chlorophyll a (Chl a) concentration in the growing season. The vertical transport of DO represented from 0 to 30% of VHODobs, while adjustments for interannual differences in hypolimnetic temperature were less important, ranging from −11 to 9% of VHODobs.
4. The mean wind speed during May made the strongest significant contribution to the variation in VHODobs. VHODobs adjusted for the vertical transport of DO and hypolimnetic temperature differences, VHODadj, was significantly related to the upper mixed layer Chl a concentration during spring.
5. Hypolimnetic anoxia (HA) ranged from 27 to 168 days per year and increased significantly over time, which undoubtedly had negative ecological consequences for the lake.
6. In similar small temperate lakes, the negative effects of eutrophication on hypolimnetic DO are likely to be exacerbated by changes in lake thermal structure brought about by a warming climate, which may undermine management efforts to alleviate the effects of anthropogenic eutrophication.