Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long–Evans rats by the α-2 adrenoreceptor antagonist yohimbine

Rationale Developing models to efficiently explore the mechanisms by which stress can mediate reinstatement of drug-seeking behavior is crucial to the development of new pharmacotherapies for alcohol use disorders. Objectives We examined the effects of multiple reinstatement sessions using the pharmacological stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a more efficient model of stress-induced reinstatement. Methods Long–Evans rats were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20% ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self-administration sessions, followed by extinction training. After reaching extinction criteria, the animals were tested once per week with yohimbine vehicle and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions or blood collection. Levels of reinstatement and plasma corticosterone (CORT) were determined each week for four consecutive weeks. Results Yohimbine induced reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks. Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol group after the first reinstatement session but remained stable for the 20% ethanol group trained without sucrose. Plasma CORT levels in response to injection of both vehicle and yohimbine were significantly higher in the ethanol-trained animals compared to sucrose controls. Conclusions The stable reinstatement in the 20% ethanol group supports the use of this training procedure in studies using within-subject designs with multiple yohimbine reinstatement test sessions. Additionally, these results indicate that the hormonal response to stressors can be altered following extinction from self-administration of relatively modest amounts of ethanol.

18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (±6.3) to 8.1 (±2.9) after 1 week of chemoradiation (P = 0.070). In nonresponders (72%), the results were 9.7 (±5.4) and 7.1 (±3.8), respectively (P = 0.003). The MTV in responders fell from 36.6 (±22.7) to 22.3 (±10.4) cm3 (P = 0.180), while in nonresponders, this fell from 35.9 (±36.7) to 31.9 (±52.7) cm3 (P = 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer. © 2006 Cancer Research UK.

Galectin-1 : a link between tumor hypoxia and tumor immune privilege

Purpose: To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression. Methods: We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CDS (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. Results: SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O 2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CDS staining (P = .01). Expression of galectin-1 and CDS were significant predictors for overall survival on multivariate analysis. Conclusion: Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege. © 2005 by American Society of Clinical Oncology.

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

Non-contact laser-scanning confocal microscopy of the human cornea in vivo

PURPOSE To investigate the utility of using non-contact laser-scanning confocal microscopy (NC-LSCM), compared with the more conventional contact laser-scanning confocal microscopy (C-LSCM), for examining corneal substructures in vivo. METHODS An attempt was made to capture representative images from the tear film and all layers of the cornea of a healthy, 35 year old female, using both NC-LSCM and C-LSCM, on separate days. RESULTS Using NC-LSCM, good quality images were obtained of the tear film, stroma, and a section of endothelium, but the corneal depth of the images of these various substructures could not be ascertained. Using C-LSCM, good quality, full-field images were obtained of the epithelium, subbasal nerve plexus, stroma, and endothelium, and the corneal depth of each of the captured images could be ascertained. CONCLUSIONS NC-LSCM may find general use for clinical examination of the tear film, stroma and endothelium, with the caveat that the depth of stromal images cannot be determined when using this technique. This technique also facilitates image capture of oblique sections of multiple corneal layers. The inability to clearly and consistently image thin corneal substructures - such as the tear film, subbasal nerve plexus and endothelium - is a key limitation of NC-LSCM.

Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age

In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18–47 years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500 μg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of <200 Joules per day, participants with personal UV exposures of 200–599 and >600 Joules per day had significantly higher depletion of serum folate (p = 0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B = −0.49; t = −3.75; p = <0.01). These data show that increasing solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

Laser-radar data fusion with Gaussian Process Implicit Surfaces

This work considers the problem of building high-fidelity 3D representations of the environment from sensor data acquired by mobile robots. Multi-sensor data fusion allows for more complete and accurate representations, and for more reliable perception, especially when different sensing modalities are used. In this paper, we propose a thorough experimental analysis of the performance of 3D surface reconstruction from laser and mm-wave radar data using Gaussian Process Implicit Surfaces (GPIS), in a realistic field robotics scenario. We first analyse the performance of GPIS using raw laser data alone and raw radar data alone, respectively, with different choices of covariance matrices and different resolutions of the input data. We then evaluate and compare the performance of two different GPIS fusion approaches. The first, state-of-the-art approach directly fuses raw data from laser and radar. The alternative approach proposed in this paper first computes an initial estimate of the surface from each single source of data, and then fuses these two estimates. We show that this method outperforms the state of the art, especially in situations where the sensors react differently to the targets they perceive.

Using image quality metrics to detect smoke-affected laser data

Field robots often rely on laser range finders (LRFs) to detect obstacles and navigate autonomously. Despite recent progress in sensing technology and perception algorithms, adverse environmental conditions, such as the presence of smoke, remain a challenging issue for these robots. In this paper, we investigate the possibility to improve laser-based perception applications by anticipating situations when laser data are affected by smoke, using supervised learning and state-of-the-art visual image quality analysis. We propose to train a k-nearest-neighbour (kNN) classifier to recognise situations where a laser scan is likely to be affected by smoke, based on visual data quality features. This method is evaluated experimentally using a mobile robot equipped with LRFs and a visual camera. The strengths and limitations of the technique are identified and discussed, and we show that the method is beneficial if conservative decisions are the most appropriate.

Laser-to-radar sensing redundancy for resilient perception in adverse environmental conditions

This paper presents an approach to promote the integrity of perception systems for outdoor unmanned ground vehicles (UGV) operating in challenging environmental conditions (presence of dust or smoke). The proposed technique automatically evaluates the consistency of the data provided by two sensing modalities: a 2D laser range finder and a millimetre-wave radar, allowing for perceptual failure mitigation. Experimental results, obtained with a UGV operating in rural environments, and an error analysis validate the approach.

Reliable automatic camera-laser calibration

Camera-laser calibration is necessary for many robotics and computer vision applications. However, existing calibration toolboxes still require laborious effort from the operator in order to achieve reliable and accurate results. This paper proposes algorithms that augment two existing trustful calibration methods with an automatic extraction of the calibration object from the sensor data. The result is a complete procedure that allows for automatic camera-laser calibration. The first stage of the procedure is automatic camera calibration which is useful in its own right for many applications. The chessboard extraction algorithm it provides is shown to outperform openly available techniques. The second stage completes the procedure by providing automatic camera-laser calibration. The procedure has been verified by extensive experimental tests with the proposed algorithms providing a major reduction in time required from an operator in comparison to manual methods.

Laser-camera data discrepancies and reliable perception in outdoor robotics

This work aims to promote integrity in autonomous perceptual systems, with a focus on outdoor unmanned ground vehicles equipped with a camera and a 2D laser range finder. A method to check for inconsistencies between the data provided by these two heterogeneous sensors is proposed and discussed. First, uncertainties in the estimated transformation between the laser and camera frames are evaluated and propagated up to the projection of the laser points onto the image. Then, for each pair of laser scan-camera image acquired, the information at corners of the laser scan is compared with the content of the image, resulting in a likelihood of correspondence. The result of this process is then used to validate segments of the laser scan that are found to be consistent with the image, while inconsistent segments are rejected. Experimental results illustrate how this technique can improve the reliability of perception in challenging environmental conditions, such as in the presence of airborne dust.

Photocatalysis on supported gold and silver nanoparticles under ultraviolet and visible light irradiation

Studies of the optical properties and catalytic capabilities of noble metal nanoparticles (NPs), such as gold (Au) and silver (Ag), have formed the basis for the very recent fast expansion of the field of green photocatalysis: photocatalysis utilizing visible and ultraviolet light, a major part of the solar spectrum. The reason for this growth is the recognition that the localised surface plasmon resonance (LSPR) effect of Au NPs and Ag NPs can couple the light flux to the conduction electrons of metal NPs, and the excited electrons and enhanced electric fields in close proximity to the NPs can contribute to converting the solar energy to chemical energy by photon-driven photocatalytic reactions. Previously the LSPR effect of noble metal NPs was utilized almost exclusively to improve the performance of semiconductor photocatalysts (for example, TiO2 and Ag halides), but recently, a conceptual breakthrough was made: studies on light driven reactions catalysed by NPs of Au or Ag on photocatalytically inactive supports (insulating solids with a very wide band gap) have demonstrated that these materials are a class of efficient photocatalysts working by mechanisms distinct from those of semiconducting photocatalysts. There are several reasons for the significant photocatalytic activity of Au and Ag NPs. (1) The conduction electrons of the particles gain the irradiation energy, resulting in high energy electrons at the NP surface which is desirable for activating molecules on the particles for chemical reactions. (2) In such a photocatalysis system, both light harvesting and the catalysing reaction take place on the nanoparticle, and so charge transfer between the NPs and support is not a prerequisite. (3) The density of the conduction electrons at the NP surface is much higher than that at the surface of any semiconductor, and these electrons can drive the reactions on the catalysts. (4) The metal NPs have much better affinity than semiconductors to many reactants, especially organic molecules. Recent progress in photocatalysis using Au and Ag NPs on insulator supports is reviewed. We focus on the mechanism differences between insulator and semiconductor-supported Au and Ag NPs when applied in photocatalytic processes, and the influence of important factors, light intensity and wavelength, in particular estimations of light irradiation contribution, by calculating the apparent activation energies of photo reactions and thermal reactions.

Measuring exposure to solar ultraviolet radiation using a dosimetric technique : understanding participant compliance issues

Personal ultraviolet dosimeters have been used in epidemiological studies to understand the risks and benefits of individuals' exposure to solar ultraviolet radiation (UVR). We investigated the types and determinants of non-compliance associated with a protocol for use of polysulphone UVR dosimeters. In the AusD Study, 1,002 Australian adults (aged 18-75 years) were asked to wear a new dosimeter on their wrist each day for 10 consecutive days to quantify their daily exposure to solar UVR. Of the 10,020 dosimeters distributed, 296 (3%) were not returned or used (Type I non-compliance) and other usage errors were reported for 763 (8%) returned dosimeters (Type II non-compliance). Type I errors were more common in participants with predominantly outdoor occupations. Type II errors were reported more frequently on the first day of measurement; weekend days or rainy days; and among females; younger people; more educated participants or those with outdoor occupations. Half (50%) the participants reported a non-compliance error on at least one day during the 10-day period. However, 92% of participants had at least 7 days of usable data without any apparent non-compliance issues. The factors identified should be considered when designing future UVR dosimetry studies.

The contributions of solar ultraviolet radiation exposure and other determinants to Serum 25-Hydroxyvitamin D concentrations in Australian adults : the AusD study

The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)2) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.