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Organophosphates in aircraft cabin air
Get PDFThe quality of aircraft cabin air on commercial aircraft has been the subject of adverse press reports for several years. One of the current issues is the potential for aircraft cabin air to become contaminated with organophosphate compounds. The primary compound causing concern is tricresyl phosphate (TCP) and the related decomposition products. It is believed that the contamination is occurring through the bleed air system supplying air to aircraft cabin. Both military and commercial pilots and cabin crew have reported symptoms such as nausea and blurred vision following smoke and fumes leaking from the jet engines and entering into the aircraft cabin. A number of investigations have suggested that the cause of these symptoms was due to the presence of additives in the engine lubricating oils, but as yet no consensus in the conclusions has been reached. The motivation for this research was to understand the problem, to determine if there was potential for air to become contaminated with organophosphate compounds and if the air was to become contaminated, was there sufficient contaminant to cause adverse health issues for cabin crew and passengers.
This research determines the potential levels of organophosphates present in aircraft cabin air. This work aims to experimentally and numerically investigate particle dispersion in aircraft cabins and the associated health risks. Firstly, experimental analysis was undertaken to determine the concentration of organophosphate, in particular TCP in aircraft engine oil and the levels present after pyrolysis. Secondly, mathematical analysis has been conducted to determine the levels of TCP in an aircraft cabin and the potential levels after several hours flight. Thirdly, numerical simulation has been performed to determine the flow paths of particles of within the aircraft cabin.
Chemical analysis has shown that TCP is present in aircraft engine oil in significant levels which would be available to be absorbed into the human body. The mathematical analysis has shown that high levels of TCP will enter the cabin and that short haul and long-haul flights presented a hazard to health. Numerical simulation has shown there would be significant levels of particles within the aircraft cabin, that could be inhaled by occupants or deposited on surfaces which would then accumulate over time.
This research has shown that there are sufficient levels of TCP contaminating aircraft cabin air to cause health issues and that particles will deposit on surfaces in sufficient quantities to cause health issues.
There are a number of recommendations which could reduce the incidences of fume event occurring such as incorporating filters or changing the type of oil used in engines
A ‘left behind’ Habitus? Understanding Local Political Disengagement Using Bourdieu
Get PDFBourdieu’s theory of social reproduction is applied to interpret the structural conditions and experiences of citizens in ‘left behind’ places (LBP) along the Cumbrian coastline (UK). The findings from a longitudinal participatory study imply a ‘left behind’ habitus where citizens disengage with local and national politics. This suggests that place-based initiatives aimed at reducing spatial inequalities, such as Levelling Up and the current devolution agenda, will be ineffective without considering the subjective, physical, distance LBP feel from political institutions. Future research needs to explore relational strategies which align the local democratic field with local civic habitus to foster liberal democracy
Probing the stability of halide perovskite films using electron spectroscopy techniques.
Get PDFHalide perovskites have attracted considerable attention from the photovoltaic research community due to the rapid advancements in reported device efficiencies. This attention is also fuelled by their easy solution processability compared to the extensive and costly crystallisation process required for traditional silicon solar cells. However, the structural instability of perovskites, particularly under high-temperature and high-humidity conditions, hampers their potential for commercialisation. This thesis attempts to explore the underlying mechanisms responsible for this instability and aims to address it through modification of the perovskite with additives.
The response of two halide perovskites, CH3NH3PbI3 and CH3NH3PbBr3, to high-temperature exposure is initially discussed utilising X-ray Photoelectron Spectroscopy (XPS). The primary objective is to understand the role of halide ions in the structural stability of perovskites. Analysis reveals that CH3NH3PbBr3 exhibits greater resistance to heating compared to CH3NH3PbI3, and a proposed degradation mechanism explains this difference in thermal stabilities. The incorporation of ionic liquids (ILs) BMIMBF4 and BMIMCl into a mixed-halide perovskite is investigated, employing a range of analytical techniques such as XPS, work function measurements, Near Edge X-ray Absorption Fine Structure (NEXAFS), Angle-resolved Hard X-ray Photoelectron Spectroscopy (Ar-HAXPES), and Near-Ambient Pressure XPS (NAP-XPS) to study the thermal and moisture resistance of the films. The role of the incorporated ILs, as well as the addition of a SnO2 electron transport layer (ETL), is investigated. Results indicate that the combined effect of ILs and SnO2 enhances the stability of the perovskite against heat and moisture. Finally, an investigation into perovskite modification using the two zwitterionic methylamines, TMAO and betaine, utilising XPS, Ar-HAXPES, and NAP-XPS is presented. The study demonstrates that TMAO-modified samples exhibit notable heat tolerance, while betaine-modified samples showcase superior moisture endurance.
Overall, this thesis provides new insights into the intrinsic mechanisms governing the degradation of perovskites and the role of additives in stabilising perovskite materials. These results could inform the future design of perovskite solar cells
In silico discovery and in vitro validation of novel CDK5 and CDK9 inhibitors with glioblastoma therapeutic potential
Get PDFGlioblastoma (GBM) is the most common glioma in adults, with a poor survival rate of only ~15 months post-diagnosis. The aggressive and incurable nature of this tumour, together with the poor efficacy of current treatment methods, underlines the importance of the discovery of novel treatment strategies for GBM. Dysregulation of both Cyclin-Dependent Kinases (CDK) -5/-9 have been implicated in a number of cancers and neurological disorders, including GBM, and previous research has demonstrated that drug-like selective inhibitors may have therapeutic potential for GBM.
Two types of CDK5/9 inhibition were explored within this thesis: type-I and -II inhibition. Type-I inhibition is the most common mechanism of kinase inhibition where inhibitors bind at the ATP-binding site when the kinase is active. However, this approach may be limited because the highly conserved nature of kinase ATP-binding sites results in selectivity and off-target toxicity concerns. Type-II inhibitors bind to the inactive state of a kinase, occupying both the ATP-binding site and a nearby hydrophobic allosteric pocket. The allosteric pocket is much less conserved, allowing the potential of increased selectivity. Importantly, type-II inhibition has been much less studied for kinases (compared to type-I) and has not previously been directly investigated for CDK5/9.
In this work, the study of type-I inhibition for CDK5 and CDK9 revealed six low micromolar flavonoid inhibitors (compounds 1, 2, 3, 6, 7 and 9) of CDK5 (IC50 < 10 μM) and six low micromolar diverse inhibitors (compounds 31, 34, 37, 40, 42 and 44) of CDK9 (IC50 < 20 μM). These were identified using in silico docking studies and validated using in vitro binding assays using isolated purified forms of CDK5/9. For CDK5, 1 (fisetin) (IC50 = 0.9 μM) and 6 (apigenin) (IC50 = 1.2 μM), were found to be the most potent. In the case of CDK9, five unique scaffolds were identified, with compound 37 and 42 (IC50 = 7.6 μM and 6.2 μM) both with a 4H,8H,9H,10H-pyrano[2,3-h]chromene-4,8-dione scaffold found to be the most potent.
In the absence of a solved crystallographic structure of CDK5/9 with a type-II inhibitor, using Desmond metadynamics (MetaD) and molecular dynamics (MD) simulations, a DFG-out/ inactive conformation of CDK5 was created for in silico screening to identify potential type-II inhibitors. Selection of a Phase I set of compounds for experimental validation resulted in the identification of two hit compounds with IC50s of 13.9 μM (compound 49) and 9.8 μM (compound 50) for CDK5/p35 inhibition, both possessing a [pyrimidin-2-yl]amino-furo[3,2-b]-furyl-urea scaffold. SAR analysis of a Phase II set of analogues using the hit scaffold revealed ten compounds with CDK5/p35 IC50s < 56 μM. Four of the most potent type-II compounds (50, 73, 82 & 88) were screened against eleven other homologous kinases revealing selective inhibition for CDK5, CDK9, CDK2 and GSK-3α/β, all of which are potential targets for GBM treatment. IC50 determinations for these four compounds against the kinases revealed low nanomolar range for CDK9 and low micromolar range for CDK5, CDK2, and GSK-3α/β. The investigation of type-II inhibition for CDK5/9 has been discussed in depth for the first time, identifying [pyrimidin-2-yl]amino-furo[3,2-b]-furyl-urea/amide as a potent scaffold for CDK5/9 lead optimisation.
Cellular studies of the best identified kinase inhibitors (six CDK5 type-I, six CDK9 type-I and four CDK5/9 type-II) were conducted to determine cell viability following 24-, 48-, and 72- hours treatment against three GBM cell lines (U87-MG, T98G and, U251-MG), investigating the effects of the type-I/-II compounds at the cellular level. The compounds were generally found to decrease cell viability in a time- and concentration- dependent manner. In terms of the type-I inhibitors, compound 31 was the most potent with IC50 of < 13.5 μM across the GBM cell lines following 72 hours treatment. Other type-I inhibitors of note were compound 1(fisetin) and 37 with IC50s of 22-40 μM and 58-87 μM following 72 hours, respectively. In the case of the four aforementioned CDK5/9 type-II inhibitors, the IC50s against the three GBM cell lines and primary cultures were determined to be ~20-35 μM for 73, 82 and 88, and ~35-85 μM for 50, following 72 hours treatment. This, therefore, reveals the ability of type-II dual inhibition of CDK5/9 as well as other kinases
that are targets for GBM (CDK2, GSK-3α/β) to result in potent effects against GBM at the cellular level, making these compounds worthy of further investigation.
The research presented here has demonstrated the potential of natural product CDK5 flavonoid inhibitors such as fisetin as well as novel identified CDK9 type-I inhibitors against GBM. In particular, the CDK9 inhibitor scaffolds of 31 and 37, 3-phenyl-5-(2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)pyrimidine-2,4(1H,3H)-dione and 4H,8H,9H,10H-pyrano[2,3-h]chromene-4,8-dione, respectively, are proposed as novel lead compounds. Furthermore, the discovery of the type-II inhibitors with dual CDK5/9 inhibition promotes a promising anti-GBM potential. Select compounds did also show effects on the cell viability of the non-cancer derived glial SVG p12 cell line, which clearly needs further investigation, but the compounds were generally found to have promising calculated pharmacokinetic profiles. As a result of this study, therefore, compounds (both type-I and type-II inhibitors) for the development of the much needed new potential therapeutic options against GBM have been identified
‘We Are Poor, Because You Are Rich’: Revisiting the Equity Phenomenon in Geopolitics
No full textMany scholars and experts agree that the global economy is as heavily rigged in favour of rich countries today, as it was years ago when many of them stuck onto their colonies to fund their recovery. Today, rich countries have control over global economic governance structures and also use their power as creditors to dictate economic policy in debtor nations. The unequal exchange between developed and developing countries is lately causing deep consternations within the corridors of developing countries. Leaders of developing countries, dismayed at this trend, are now calling for the democratisation of institutions of global economic governance, so that poor countries could have a fairer say in setting the terms of trade and finance and also for new development patterns that can help share the fruits of the international economy much more fairly
Modelling of wildland fire spread using empirical approach analysing the effect of moisture, wind, and slope
Get PDFDue to rapid climate change, wildfires are an increasing risk to human life and economy. To prevent their occurrence and reduce their intensity, computational methods have been developed to study and simulate wildfire spread. Medium scale experiments and thermogravimetric analysis is conducted for Pinus Sylvestris Needle. Results from numerical analysis using level set model were validated using experimental data. And a parametric study was performed to study the effect of fuel moisture fraction, wind and slope to surface vegetation fire behaviour. Numerical data, including temperature and rate of spread, are analysed and limitations of model is also discussed
Eight letters to Claudette (2021)
No full textAn exchange of letters between artists Lubaina Himid and Claudette Johnson, written over the course of 2021. Himid and Johnson first met in October 1982 at the First National Black Art Convention at Wolverhampton Polytechnic, while studying Theatre Design and Fine Art respectively. In the correspondence, the two discuss their approach to painting and drawing, from formative studies at University to the present, and the use of light and colour in their work. At the time, Johnson was preparing for her solo exhibition of new work "Still Here" at Hollybush Gardens, London
Physiological and clinical parameters under different protocols of total intravenous anesthesia in llama (Lama glama) undergoing unilateral ovariectomy
Get PDFBackground: The limited and detailed literature on total intravenous anesthesia (TIVA), as well as the clinical indications for unilateral ovariectomy in llamas, are not well-defined. Therefore, it is necessary to understand the anesthetic events and the surgical intervention in this species.
Aim: The objective of this study was to evaluate the intraoperative physiological and clinical parameters in llamas undergoing unilateral ovariectomy, under three protocols of TIVA.
Methods: The study was conducted with 30 healthy female llamas. Three groups were considered G1: Pre-anaesthetic - xylazine i/v, Induction: ketamine. Maintenance: fentanyl and ketamine (FLK) (fentanyl + lidocaine + ketamine) by continuous infusion. G2: Pre-anaesthetic - midazolam + tramadol + ketamine i/v. Induction – propofol. Maintenance,
boluses of 20% of the total induction dose were added if required. G3: Pre-anaesthetic - midazolam + xylazine i/v. Induction: ketamine. Maintenance: with 20% of the total induction. Physiological parameters were evaluated at 5, 15, and 30 minutes.
Results: The heart rate, respiratory rate, arterial oxygen saturation (SpO2 ), and rectal temperature (RT) of the groups showed significant differences at some point in the evaluation, presenting a degree of bradycardia and bradypnea in G1 and G2. A drop in SpO2 was seen at minute 5 in all groups, because of respiratory depression post-anesthetic induction, subsequently, the values increased, with better saturation in G2. RT remained similar in the groups until minute 20, then there was a significant decrease in G2. G1 showed significant fluctuations for SpO2 and G2 for RT. The majority of animals from G1 and G3 maintained marked relaxation of the abdomen and limbs, anal sphincter (G3), and mandible (G1). Salivation and tearing were an infrequent sign in G2. All animals from G3 presented some degree of sensitivity to the abdominal wall. The average duration of the surgery was 14 minutes, and the shortest anesthetic recovery time occurred in G2 (28 minutes).
Conclusion: The animals of the three groups showed significant differences in their physiological and clinical parameters, in response to the agents used. The G1 protocol: xylazine, ketamine y FLK. Demonstrated better physiological and hemodynamic stability with an acceptable level of surgical anesthesia
Immediate Effect of Uddiyana Bandha on Heart Rate Variability in Patients with Hypertension: A Randomised Controlled Study
Get PDFBackground
Hypertension, a prevalent cardiovascular condition, is linked to autonomic nervous system dysregulation, often evidenced by reduced heart rate variability (HRV). Yoga, particularly Uddiyana Bandha, may influence autonomic control and improve HRV, thus offering potential benefits for hypertension management.
Purpose
This study intended to assess the impact of the regular use of Uddiyana Bandha practice on HRV among hypertensive patients.
Methods
This randomised controlled study included 60 hypertensive patients aged between 40 and 60. Participants were randomised into an intervention group practicing Uddiyana Bandha (n = 30) and a control group with no intervention (n = 30). The outcome measures included time and frequency domain HRV variables, specifically the standard deviation of NN intervals (SDNN), the square root of the mean squared differences of successive NN intervals (RMSSD), high-frequency (HF) and low-frequency (LF) components in normalised units (n.u), and the LF/HF ratio. These were assessed both before and immediately after the intervention. The intervention group performed three rounds of Uddiyana Bandha under supervision, while the control group rested quietly for an equivalent duration.
Results
The Uddiyana Bandha group demonstrated significant (p < .05) improvements in HRV parameters post-intervention compared to the control group. Mean RR interval, SDNN and RMSSD increased immediately after Uddiyana Bandha practice. The HF component (n.u) increased, while the LF component (n.u) and LF/HF ratio decreased (p < .05), indicating enhanced parasympathetic activity. No significant changes were observed in the control group.
Conclusion
Uddiyana Bandha’s practice immediately has notable effects on HRV in hypertensive patients, showing better autonomic balance and cardiovascular performance. These results suggest Uddiyana Bandha as a possible non-pharmacological strategy for hypertension management. Future studies with larger sample sizes and longer durations are needed to support these results and explore long-term effects
The putative center in NGC 1052
Get PDFContext. Many active galaxies harbor powerful relativistic jets, however, the detailed mechanisms of their formation and acceleration remain poorly understood.
Aims. To investigate the area of jet acceleration and collimation with the highest available angular resolution, we study the innermost region of the bipolar jet in the nearby low-ionization nuclear emission-line region (LINER) galaxy NGC 1052.
Methods. We combined observations of NGC 1052 taken with VLBA, GMVA, and EHT over one week in the spring of 2017. Our study is focused on the size and continuum spectrum of the innermost region containing the central engine and the footpoints of both jets. We employed a synchrotron-self absorption model to fit the continuum radio spectrum and we combined the size measurements from close to the central engine out to ∼1 pc to study the jet collimation.
Results. For the first time, NGC 1052 was detected with the EHT, providing a size of the central region in-between both jet bases of 43 μas perpendicular to the jet axes, corresponding to just around 250 RS (Schwarzschild radii). This size estimate supports previous studies of the jets expansion profile which suggest two breaks of the profile at around 3 × 103 RS and 1 × 104 RS distances to the core. Furthermore, we estimated the magnetic field to be 1.25 Gauss at a distance of 22 μas from the central engine by fitting a synchrotron-self absorption spectrum to the innermost emission feature, which shows a spectral turn-over at ∼130 GHz. Assuming a purely poloidal magnetic field, this implies an upper limit on the magnetic field strength at the event horizon of 2.6 × 104 Gauss, which is consistent with previous measurements.
Conclusions. The complex, low-brightness, double-sided jet structure in NGC 1052 makes it a challenge to detect the source at millimeter (mm) wavelengths. However, our first EHT observations have demonstrated that detection is possible up to at least 230 GHz. This study offers a glimpse through the dense surrounding torus and into the innermost central region, where the jets are formed. This has enabled us to finally resolve this region and provide improved constraints on its expansion and magnetic field strength