Gas sensors for climate research

The availability of datasets providing information on the spatial and temporal evolution of greenhouse gas concentrations is of high relevance for the development of reliable climate simulations. However, current gas detection technologies do not allow for obtaining high-quality data at intermediate spatial scales with high temporal resolution. In this regard the deployment of a wireless gas sensor network equipped with in situ gas analysers may be a suitable approach. Here we present a novel, non-dispersive infrared absorption spectroscopy (NDIR) device that can possibly act as a central building block of a sensor node to provide high-quality data of carbon dioxide (CO2) concentrations under field conditions at a high measurement rate. Employing a gas-based, photoacoustic detector we demonstrate that miniaturized, low-cost, and low-power consuming CO2 sensors may be built. The performance is equal to that of standard NDIR devices but at a much reduced optical path length. Because of the spectral properties of the photoacoustic detector, no cross-sensitivities to humidity exist.</p

Undergraduate medical research: the student perspective

Background: Research training is essential in a modern undergraduate medical curriculum. Our evaluation aimed to (a) gauge students&#x2019; awareness of research activities, (b) compare students&#x2019; perceptions of their transferable and research-specific skills competencies, (c) determine students&#x2019; motivation for research and (d) obtain students&#x2019; personal views on doing research. Methods: Undergraduate medical students (N=317) completed a research skills questionnaire developed by the Centre for Excellence in Teaching and Learning in Applied Undergraduate Research Skills (CETL-AURS) at Reading University. The questionnaire assessed students&#x2019; transferable skills, research-specific skills (e.g., study design, data collection and data analysis), research experience and attitude and motivation towards doing research. Results: The majority of students are motivated to pursue research. Graduate entrants and male students appear to be the most confident regarding their research skills competencies. Although all students recognise the role of research in medical practice, many are unaware of the medical research activities or successes within their university. Of those who report no interest in a career incorporating research, a common perception was that researchers are isolated from patients and clinical practice. Discussion: Students have a narrow definition of research and what it entails. An explanation for why research competence does not align more closely with research motivation is derived from students&#x2019; lack of understanding of the concept of translational research, as well as a lack of awareness of the research activity being undertaken by their teachers and mentors. We plan to address this with specific research awareness initiatives

Hyperphosphorylation and Cleavage at D421 Enhance Tau Secretion

It is well established that tau pathology propagates in a predictable manner in Alzheimer’s disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD’s patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF

In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna canaliculus

BACKGROUND: Inflammation is a predominant characteristic of autoimmune diseases which is characterized by the increased expression of pro-inflammatory cytokines. Soon to be published work from our laboratory has shown that ingestion of Perna canaliculus prevents the development of autoimmune diseases such as Systemic Lupus Erythematosus and rheumatoid arthritis in laboratory animals. The current paper attempts to illustrate how Perna can alleviate inflammation by modulating inflammatory cytokines, cyclooxygenase enzymes and Immunoglobulin-G (IgG) levels. METHODS: In the present study, hydrochloric acid [HCl] and Tween-20 were used to develop extracts of Perna. These extracts were assayed for protein content. Increasing concentrations of these extracts were then tested in cell culture for modulation of inflammatory cytokine, cyclooxygenase enzymes and IgG levels. Parallel tests were run using an available glycogen extract of Perna as a comparison to our in-house laboratory preparations. RESULTS: Tween-20 Perna extracts were found to be more stable and less toxic in cell culture than HCl digest of Perna. They also assayed higher in protein content that HCl extracts. Although both extracts inhibited IgG production in V2E9 hybridomas, Tween-20 extracts were more consistent in IgG suppression than HCl extracts. Overall Tween-20 extracts effectively decreased levels of TNF-α, IL-1, IL-2 and IL-6 as observed using cytokine bioassays. Twenty micrograms of Tween-20 Perna extracts induced such significant decreases in inflammatory cytokine production that when tested on sensitive cell lines, they very nearly abolished the decrease in viability induced by these cytokines. Tween-20 extracts effectively inhibited both COX-1 and COX-2 cyclooxygenase activity. As a comparison, the glycogen extract also demonstrated a similar though weaker effect on COX-1 and COX-2 enzymes. The active components of both extracts (Tween-20 and glycogen) were observed to possess molecular weights above 100 kDa. Although the anti-cytokine activity of the Tween-20 extract was destroyed by Proteinase-K treatment, the anti-COX-1 and anti-COX-2 activity of both the extracts were not sensitive to protease treatment. CONCLUSION: We have successfully demonstrated modulation in the levels of inflammatory cytokines, cyclooxygenase enzymes and immunoglobulins by our in-house laboratory preparations of Perna canaliculus, whereby suggesting an immunomodulatory role of Perna canaliculus in regulating inflammation

Modelling the impact of atherosclerosis on drug release and distribution from coronary stents

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions

Topographic Spread of Inferior Colliculus Activation in Response to Acoustic and Intracochlear Electric Stimulation

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based single-shank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41383/1/10162_2004_Article_4026.pd

Testing the sensitivity of Tract-Based Spatial Statistics to simulated treatment effects in preterm neonates

Early neuroimaging may provide a surrogate marker for brain development and outcome after preterm birth. Tract-Based Spatial Statistics (TBSS) is an advanced Diffusion Tensor Image (DTI) analysis technique that is sensitive to the effects of prematurity and may provide a quantitative marker for neuroprotection following perinatal brain injury or preterm birth. Here, we test the sensitivity of TBSS to detect diffuse microstructural differences in the developing white matter of preterm infants at term-equivalent age by modelling a 'treatment' effect as a global increase in fractional anisotropy (FA). As proof of concept we compare these simulations to a real effect of increasing age at scan. 3-Tesla, 15-direction diffusion tensor imaging (DTI) was acquired from 90 preterm infants at term-equivalent age. Datasets were randomly assigned to 'treated' or 'untreated' groups of increasing size and voxel-wise increases in FA were used to simulate global treatment effects of increasing magnitude in all 'treated' maps. 'Treated' and 'untreated' FA maps were compared using TBSS. Predictions from simulated data were then compared to exemplar TBSS group comparisons based on increasing postmenstrual age at scan. TBSS proved sensitive to global differences in FA within a clinically relevant range, even in relatively small group sizes, and simulated data were shown to predict well a true biological effect of increasing age on white matter development. These data confirm that TBSS is a sensitive tool for detecting global group-wise differences in FA in this population