Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in the mouse skin model adopted for epidermal powdered immunization

Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely that the relative volumetric distribution of LCs and keratinocytes within the epidermis impacts on the efficacy of Gene Gun immunization protocols. This study quantified the three-dimensional (3D) distribution of LCs and keratinocytes in the mouse skin model with a near-infrared multiphoton laser-scanning microscope (NIR-MPLSM). Stratum corneum (SC) and viable epidermal thickness measured with MPLSM was found in close agreement with conventional histology. LCs were located in the vertical plane at a mean depth of 14.9 mum, less than 3 mum above the dermo-epidermal boundary and with a normal histogram distribution. This likely corresponds to the fact that LCs reside in the suprabasal layer (stratum germinativum). The nuclear volume of keratinocytes was found to be approximately 1.4 times larger than that of resident LCs (88.6 mum3). Importantly, the ratio of LCs to keratinocytes in mouse ear skin (1:15) is more than three times higher than that reported for human breast skin (1:53). Accordingly, cross-presentation may be more significant in clinical Gene Gun applications than in pre-clinical mouse studies. These interspecies differences should be considered in pre-clinical trials using mouse models.

Reduced nephron number and glomerulomegaly in Australian Aborigines: A group at high risk for renal disease and hypertension

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines-202000 fewer glomeruli per kidney, or an estimated 404000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without-250000 fewer per kidney (P=0.03), or 500000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.

Electrical impedance tomography in extremely prematurely born infants and during high frequency oscillatory ventilation analyzed in the frequency domain

Functional electrical impedance tomography (EIT) measures relative impedance change that occurs in the chest during a distinct observation period and an EIT image describing regional relative impedance change is generated. Analysis of such an EIT image may be erroneous because it is based on an impedance signal that has several components. Most of the change in relative impedance in the chest is caused by air movement but other physiological events such as cardiac activity change in end expiratory level or pressure swings originating from a ventilator circuit can influence the impedance signal. We obtained EIT images and signals in spontaneously breathing healthy adults, in extremely prematurely born infants on continuous positive airway pressure and in ventilated sheep on conventional mechanical or high frequency oscillatory ventilation (HFOV). Data were analyzed in the frequency domain and results presented after band pass filtering within the frequency range of the physiological event of interest. Band pass filtering of EIT data is necessary in premature infants and on HFOV to differentiate and eliminate relative impedance changes caused by physiological events other than the one of interest.

A new indexing method for high dimensional dataset

Indexing high dimensional datasets has attracted extensive attention from many researchers in the last decade. Since R-tree type of index structures are known as suffering curse of dimensionality problems, Pyramid-tree type of index structures, which are based on the B-tree, have been proposed to break the curse of dimensionality. However, for high dimensional data, the number of pyramids is often insufficient to discriminate data points when the number of dimensions is high. Its effectiveness degrades dramatically with the increase of dimensionality. In this paper, we focus on one particular issue of curse of dimensionality; that is, the surface of a hypercube in a high dimensional space approaches 100% of the total hypercube volume when the number of dimensions approaches infinite. We propose a new indexing method based on the surface of dimensionality. We prove that the Pyramid tree technology is a special case of our method. The results of our experiments demonstrate clear priority of our novel method.

Mud, algae or seagrass: An assessment of remote sensing techniques for mapping inter-tidal seagrass cover and composition in turbid tropical environments

Large areas of tropical sub- and inter-tidal seagrass beds occur in highly turbid environments and cannot be mapped through the water column. The purpose of this project was to determine if and how airborne and satellite imaging systems could be used to map inter-tidal seagrass properties along the wet-tropics coast in north Queensland, Australia. The work aimed to: (1) identify the minimum level of seagrass foliage cover that could be detected from airborne and satellite imagery; and (2) define the minimum detectable differences in seagrass foliage cover in exposed intertidal seagrass beds. High resolution spectral-reflectance data (2040 bands, 350 – 2500nm) were collected over 40cm diameter plots from 240 sites on Magnetic Island, Pallarenda Beach and Green Island in North Queensland at spring low tides in April 2006. The seagrass species sampled were: Thalassia hemprechii, Halophila ovalis, Halodule uninerivs; Syringodium isoetifolium, Cymodocea serrulata, and Cymodoea rotundata. Digital photos were captured for each plot and used to derive estimates of seagrass species cover, epiphytic growth, micro- and macro-algal cover, and substrate colour. Sediment samples were also collected and analysed to measure the concentration of Chlorophyll-a associated with benthic micro-algae. The field reflectance spectra were analysed in combination with their corresponding seagrass species foliage cover levels to establish the minimum foliage projective cover required for each seagrass to be significantly different from bare substrate and substrate with algal cover. This analysis was repeated with reflectance spectra resampled to the bandpass functions of Quickbird, Ikonos, SPOT 5 and Landsat 7 ETM. Preliminary results indicate that conservative minimum detectable seagrass cover levels across most the species sampled were between 30%- 35% on dark substrates. Further analysis of these results will be conducted to determine their separability and satellite images and to assess the effects epiphytes and algal cover.

Marking high-technology market evolution through the foci of market stories:the case of local area networks

Previous research suggests that changing consumer and producer knowledge structures play a role in market evolution and that the sociocognitive processes of product markets are revealed in the sensemaking stories of market actors that are rebroadcasted in commercial publications. In this article, the authors lend further support to the story-based nature of market sensemaking and the use of the sociocognitive approach in explaining the evolution of high-technology markets. They examine the content (i.e., subject matter or topic) and volume (i.e., the number) of market stories and the extent to which content and volume of market stories evolve as a technology emerges. Data were obtained from a content analysis of 10,412 article abstracts, published in key trade journals, pertaining to Local Area Network (LAN) technologies and spanning the period 1981 to 2000. Hypotheses concerning the evolving nature (content and volume) of market stories in technology evolution are tested. The analysis identified four categories of market stories - technical, product availability, product adoption, and product discontinuation. The findings show that the emerging technology passes initially through a 'technical-intensive' phase whereby technology related stories dominate, through a 'supply-push' phase, in which stories presenting products embracing the technology tend to exceed technical stories while there is a rise in the number of product adoption reference stories, to a 'product-focus' phase, with stories predominantly focusing on product availability. Overall story volume declines when a technology matures as the need for sensemaking reduces. When stories about product discontinuation surface, these signal the decline of current technology. New technologies that fail to maintain the 'product-focus' stage also reflect limited market acceptance. The article also discusses the theoretical and managerial implications of the study's findings. © 2002 Elsevier Science Inc. All rights reserved.

The relationship between market share and information in a high-tech industry

The role of information in high-technology markets is critical (Dutta, Narasimhan and Rajiv 1999; Farrell and Saloner 1986; Weiss and Heide 1993). In these markets, the volatility and volume of information present managers and researchers with the considerable challenge of monitoring such information and examining how potential customers may respond to it. This article examines the effects of the type and volume of information on the market share of different technological standards in the Local Area Networks (LAN) industry. We identify three different types of information: technological, availability and adoption. Our empirical application suggests that all three types of information have significant effects on the market share of a technological standard, but their direction and magnitude differ. More specifically, technology-related information is negatively related to market share as it demonstrates that the underlying technology is immature and still evolving. Both availability and adoption-related information have a positive effect on market share, but the former is larger than the latter. We conclude that high-tech firms should emphasize the dissemination of information, especially availability-related, as part of their promotional strategy for a new technology. Otherwise, they may risk missing an opportunity to achieve a higher share and establish their market presence.

The effects of metallurgical variables on the mechanical properties of high-chromium cast irons

The.use of high-chromium cast irons for abrasive wear resistance is restricted due to their poor fracture toughness properties. An.attempt was made to improve the fracture characteristics by altering the distribution, size and.shape of the eutectic carbide phase without sacrificing their excellent wear resistance. This was achieved by additions of molybdenum or tungsten followed by high temperature heat treatments. The absence of these alloying elements or replacement of them with vanadium or manganese did not show any significant effect and the continuous eutectic carbide morphology remained the same after application of high temperature heat treatments. The fracture characteristics of the alloys with these metallurgical variables were evaluated for both sharp-cracks and blunt notches. The results were used in conjunction with metallographic and fractographic observations to establish possible failure mechanisms. The fracture mechanism of the austenitic alloys was found to be controlled not only by the volume percent but was also greatly influenced by the size and distribution of the eutectic carbides. On the other hand, the fracture mechanism of martensitic alloys was independent of the eutectic carbide morphology. The uniformity of the secondary carbide precipitation during hardening heat treatments was shown to be a reason for consistant fracture toughness results being obtained with this series of alloys although their eutectic carbide morphologies were different. The collected data were applied to a model which incorporated the microstructural parameters and correlated them with the experimentally obtained valid stress intensity factors. The stress intensity coefficients of different short-bar fracture toughness test specimens were evaluated from analytical and experimental compliance studies. The.validity and applicability of this non-standard testing technique for determination of the fracture toughness of high-chromium cast irons were investigated. The results obtained correlated well with the valid results obtained from standard fracture toughness tests.

The role of organoclay in promoting co-continuous morphology in high-density poly(ethylene)/poly(amide) 6 blends

The effect of organically modified clay on the morphology, rheology and mechanical properties of high-density polyethylene (HDPE) and polyamide 6 (PA6) blends (HDPE/PA6 = 75/25 parts) is studied. Virgin and filled blends were prepared by melt compounding the constituents using a twin-screw extruder. The influence of the organoclay on the morphology of the hybrid was deeply investigated by means of wide-angle X-ray diffractometry, transmission and scanning electron microscopies and quantitative extraction experiments. It has been found that the organoclay exclusively places inside the more hydrophilic polyamide phase during the melt compounding. The extrusion process promotes the formation of highly elongated and separated organoclay-rich PA6 domains. Despite its low volume fraction, the filled minor phase eventually merges once the extruded pellets are melted again, giving rise to a co-continuous microstructure. Remarkably, such a morphology persists for long time in the melt state. A possible compatibilizing action related to the organoclay has been investigated by comparing the morphology of the hybrid blend with that of a blend compatibilized using an ethylene–acrylic acid (EAA) copolymer as a compatibilizer precursor. The former remains phase separated, indicating that the filler does not promote the enhancement of the interfacial adhesion. The macroscopic properties of the hybrid blend were interpreted in the light of its morphology. The melt state dynamics of the materials were probed by means of linear viscoelastic measurements. Many peculiar rheological features of polymer-layered silicate nanocomposites based on single polymer matrix were detected for the hybrid blend. The results have been interpreted proposing the existence of two distinct populations of dynamical species: HDPE not interacting with the filler, and a slower species, constituted by the organoclay-rich polyamide phase, which slackened dynamics stabilize the morphology in the melt state. In the solid state, both the reinforcement effect of the filler and the co-continuous microstructure promote the enhancement of the tensile modulus. Our results demonstrate that adding nanoparticles to polymer blends allows tailoring the final properties of the hybrid, potentially leading to high-performance materials which combine the advantages of polymer blends and the merits of polymer nanocomposites.

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder:significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation.

Design and implementation of production systems for high variety electronics assembly

Information technology companies are having to broaden their overall strategic view in deference to the premise that it is better to be market-driven than technology-led. Cost and technical performance are no longer the only considerations, as quality and service now demand equal recognition. The production of a high volume single item has given way to that of low volume multiple items, which in turn requires some modification of production systems and brings flexible manufacturing, Just-in-Time production and total quality control into sharper focus for the achievement of corporate objectives.

High permeability of the anionic form restricts accumulation of indomethacin by cultured gastric surface epithelial cells exposed to low apical pH

The 'ion-trapping' hypothesis suggests that the intracellular concentration of acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be much higher than in the gastric lumen, and that such accumulation could contribute to their gastrotoxicity. Our aim was to examine the effect of the pH of the apical medium on the apical to basal transfer of the acidic drug indomethacin (pK a 4.5) across a gastric mucous epithelial cell monolayer, and to determine whether indomethacin accumulated in cells exposed to a low apical pH. Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture inserts (Transwells®) for 72 h. Transfer and accumulation of [ 14C] indomethacin were assessed by scintillation counting. Transfer of [ 3H]mannitol and measurement of trans-epithelial electrical resistance were used to assess integrity of the monolayer. Distribution of [ 14C] urea was used to estimate the intracellular volume of the monolayer. The monolayer was not disrupted by exposure of the apical face to media of pH ≥ 3, or by indomethacin. Transfer of indomethacin (12 μM) to the basal medium increased with decreasing apical medium pH. The apparent permeability of the undissociated acid was estimated to be five times that of the anion. The intracellular concentration of indomethacin was respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and 3.0. In conclusion, this study represents the first direct demonstration that indomethacin accumulates in gastric epithelial cells exposed to low apical pH. However, accumulation of indomethacin was moderate and the predictions of the ion-trapping hypothesis were not met, probably due to the substantial permeability of anionic indomethacin across membranes. © 2006 Elsevier B.V. All rights reserved.

Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1-3.9 Hz), theta (4-7.9 Hz) alpha (8-12.9 Hz), beta1 (13-19.9 Hz), beta2 (20-29.9 Hz) and gamma (30-45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized "hypnotic-state". © 2014 Jamieson and Burgess.

Effect of cooling rate on intercritically reheated microstructure and toughness in high strength low alloy steel

High strength low alloy steels have been shown to be adversely affected by the existence of regions of poor impact toughness within the heat affected zone (HAZ) produced during multipass welding. One of these regions is the intercritically reheated coarse grained HAZ or intercritical zone. Since this region is generally narrow and discontinuous, of the order of 0.5 mm in width, weld simulators are often employed to produce a larger volume of uniform microstructure suitable for toughness assessment. The steel usedfor this study was a commercial quenched and tempered steel of 450 MN m -2 yield strength. Specimen blanks were subjected to a simulated welding cycle to produce a coarse grained structure of upper bainite during the first thermal cycle, followed by a second thermal cycle where the peak temperature T p2 was controlled. Charpy tests carried out for T p2 values in the range 650-850°C showed low toughness for T p2 values between 760 and 790°C, in the intercritical regime. Microstructural investigation of the development of grain boundary martensite-retained austenite (MA) phase has been coupled with image analysis to measure the volume fraction of MAformed. Most of the MA constituent appears at the prior austenite grain boundaries during intercritical heating, resulting in a 'necklace' appearance. For values of T p2 greater than 790°C the necklace appearance is lost and the second phase areas are observed throughout the structure. Concurrent with this is the development of the fine grained, predominantly ferritic structure that is associated with the improvement in toughness. At this stage the microstructure is transforming from the intercritical regime structure to the supercritically reheated coarse grained HAZ structure. The toughness improvement occurs even though the MA phase is still present, suggesting that the embrittlement is associated with the presence of a connected grain boundary network of the MA phase. The nature of the second phase particles can be controlled by the cooling rate during the second cycle and variesfrom MA phase at high cooling rates to a pearlitic structure at low cooling rates. The lowest toughness of the intercritical zone is observed only when MA phase is present. The reason suggested for this is that only the MA particles debond readily, a number of debonded particles in close proximity providing sufficient stress concentration to initiate local cleavage. © 1993 The Institute of Materials.

Large volume metrology technologies for the light controlled factory

In the Light Controlled Factory part-to-part assembly and reduced weight will be enabled through the use of predictive fitting processes; low cost high accuracy reconfigurable tooling will be made possible by active compensation; improved control will allow accurate robotic machining; and quality will be improved through the use of traceable uncertainty based quality control throughout the production system. A number of challenges must be overcome before this vision will be realized; 1) controlling industrial robots for accurate machining; 2) compensation of measurements for thermal expansion; 3) Compensation of measurements for refractive index changes; 4) development of Embedded Metrology Tooling for in-tooling measurement and active tooling compensation; and 5) development of Software for the Planning and Control of Integrated Metrology Networks based on Quality Control with Uncertainty Evaluation and control systems for predictive processes. This paper describes how these challenges are being addressed, in particular the central challenge of developing large volume measurement process models within an integrated dimensional variation management (IDVM) system.