OAK (Online Access to Knowledge) Commons (Young Harris College)
Not a member yet
33676 research outputs found
Sort by
Real-Time Fluctuations in Single-Molecule Rotaxane Experiments Reveal an Intermediate Weak Binding State During Shuttling
No full textWe report on the use of AFM to identify and characterize an intermediate state in macrocycle shuttling in a hydrogen bonded amide-based molecular shuttle. The [2]rotaxane consists of a benzylic amide macrocycle mechanically locked onto a thread that bears both fumaramide and succinic amide-ester sites, each of which can bind to the macrocycle through up to four intercomponent hydrogen bonds. Using AFM-based single-molecule force spectroscopy we mechanically triggered the translocation of the ring between the two principal binding sites (‘stations’) on the axle. Equilibrium fluctuations reveal another interacting site involving the two oxygen atoms in the middle of the thread. We characterized the ring occupancy distribution over time, which confirms the intermediate in both shuttling directions. The study provides evidence of weak hydrogen bonds that are difficult to detect using other methods and shows how the composition of the thread can significantly influence the shuttling dynamics by slowing down the ring motion between the principal binding sites. More generally the study illustrates the utility that single-molecule experiments, such as force spectroscopy, can offer for elucidating the structure and dynamics of synthetic molecular machines
Alpha entrainment drives pain relief using visual stimulation in a sample of chronic pain patients. A proof-of-concept controlled study.
No full textOne-third of the population in the UK and worldwide struggle with chronic pain. Entraining brain alpha activity through non-invasive visual stimulation has been shown to reduce experimental pain in healthy volunteers. Neural oscillations entrainment offers a potential non-invasive and non-pharmacological intervention for patients with chronic pain, which can be delivered in the home setting and has the potential to reduce use of medications. However, evidence supporting its use in patients with chronic pain is lacking. This study explores whether a) alpha entrainment increase alpha power in patients and b) whether this increase in alpha correlates with analgesia. 28 patients with chronic pain sat in a comfortable position and underwent 4-minute visual stimulation using customised goggles at 10 Hz (alpha) and 7 Hz (control) frequency blocks in a randomised cross-over design. 64-channel Electroencephalography (EEG) and 11-point Numeric Rating Scale (NRS) pain intensity and pain unpleasantness scores were recorded before and after stimulation. EEG analysis revealed frontal alpha power was significantly higher when stimulating at 10 Hz when compared to 7 Hz. There was a significant positive correlation between increased frontal alpha and reduction in pain intensity (r=0.33, p<0.05) and pain unpleasantness (r=0.40, p<0.05) in the 10 Hz block. This study provides the first proof of concept that changes in alpha power resulting from entrainment correlate with an analgesic response in patients with chronic pain. Further studies are warranted to investigate dose-response parameters and equivalence to analgesia provided by medications
Gas Flow Models of Shale: A Review
No full textConventional flow models based on Darcy's flow physics fail to model shale gas production data accurately. The failure to match field data and laboratory-scale evidence of non-Darcy flow has led researchers to propose various gas-flow models for the shale reservoirs. There is extensive evidence that suggests the size of the pores in shale is microscopic in the range of a few to hundreds of nanometers (also known as nanopores). These small pores are mostly associated with the shale's organic matter portion, resulting in a dual pore system that adds to the gas flow complexity. Unlike Darcy's law, which assumes that a dominant viscous flux determines a rock's permeability, shale's permeability leads to other flow processes besides viscous flow such as gas slippage and Knudsen diffusion. This paper reviews the dominant gas-flow processes in a single nanopore based on theoretical models and molecular dynamics simulations, and Lattice Boltzmann modeling. We extend the review to pore network models used to study the gas permeability of shale
On the Implementation of OPF Based Setpoints for Active Distribution Networks
No full textIn the context of active distribution networks, AC Optimal Power Flow (OPF) has shown great potential to calcu-late setpoints for controllable devices. Although considerable literature exists, temporal aspects that may affect the actual exe-cution of these setpoints are rarely investigated. Due to the di-verse operating characteristics of controllable devices (i.e., de-lays, ramp rates and deadbands), when these setpoints are exe-cuted by multiple devices without adequate considerations, the resulting outcome can differ drastically from what is expected; leading to violations of network constraints and excessive control actions. Therefore, this work proposes a series of necessary adap-tations within the controllers of existing devices as well as in the OPF formulation to cater for the diversity in operating charac-teristics, ensuring that calculated setpoints are adequately im-plemented by controllable devices. This involves the direct con-trol of conventional devices and enforcing a new ramping behav-ior for inverter-interfaced devices. Furthermore, a linear, mixed-integer formulation is proposed to handle discrete devices and improve scalability in large networks. Co-simulation results (us-ing a UK test network with the objective of maximizing renewa-ble energy production and considering 1s time-step) demonstrate that, by catering for the operating characteristics of controllable devices, the expected outcome from OPF-based setpoints can be achieved
“Why is it so different now I’m bisexual?”:young bisexual people’s experiences of identity, belonging, self-injury, and COVID19
No full textBisexual people demonstrate higher rates of Non-Suicidal Self-Injury (NSSI) in comparison to other groups. This study aimed to explore bisexual people’s experiences of sexuality, NSSI and the COVID19 pandemic. Fifteen bisexual people (16-25 years old) with experience of NSSI participated in online qualitative interviews. Thematic analysis was used. Preliminary findings were shared with a subset of participants for member-checking. Participants described experiences of falling between the binary worlds of heterosexuality and homosexuality and described discrimination and invalidation related to this. Lack of access to positive bisexual representation contributed to feelings of self-loathing, with NSSI used to manage emotions or self-punish. The effect of lockdown was not clear cut, depending on personal circumstances and meanings of social interaction for participants. There is a need for greater recognition of significant societal narratives around bisexuality within clinical formulations of mental health difficulties and NSSI within this population
Perspectives on glucocorticoid usage in patients with adult inflammatory myopathy
No full textObjective: To describe the patient perspective on glucocorticoid (GC) treatment and adverse effects (AEs) in idiopathic inflammatory myopathy (IIM). Methods: An online survey was distributed to patients with adult-onset IIM using the Myositis UK page on Healthunlocked.com, an online social network for health. Respondents were asked to rate the severity of AEs they attributed to GCs on a Likert scale (0-5), and to report concerns and overall experience of GC treatment. Results: The survey was completed by 122 respondents. The median reported current daily dose of prednisolone was 15 mg (interquartile range [IQR] 8, 25) and median treatment duration 5.3 years (IQR 3.4, 8.0) at the time of survey completion. Only 54% of respondents “agreed” or “strongly agreed” that the information provided to them about GC treatment was adequate. AEs rated most severe by respondents were weight gain, moon face, sleep disturbances, increased hunger. The duration of GC treatment weakly correlated with the mean number of reported AEs (p=0.004) and mean severity of AEs (p=0.017). There was an inverse relationship between age and acne, stretch marks, hair loss, facial hair, nausea, and heartburn (p<0.05). Conclusion: In this first study of patient-reported experiences of GCs specifically in IIM, we describe the burden of treatment and highlight the unmet need for safe and well tolerated treatments. We report that patients with IIM often remain on long-term GC treatment at moderate doses, and that AEs are common. The reported data will be useful in planning discussions with patients regarding adherence to their treatment options
Laboratory Safety of Dupilumab in Patients Aged 6 to < 12 Years with Severe Atopic Dermatitis: Results from a Phase 3 Clinical Trial
No full textBackground: Previous studies of dupilumab in adolescents and adults with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful adverse changes in laboratory parameters. Objective: To assess laboratory outcomes in children aged 6 to < 12 years with severe AD in a randomized, placebo-controlled, phase 3 trial of dupilumab. Methods: Children aged 6 to < 12 years with severe AD were randomized 1:1:1 to 16 weeks of dupilumab 300 mg every 4 weeks, 100 or 200 mg every two weeks, or matching placebo, all with concomitant topical corticosteroids (TCS). Blood samples were collected at baseline and Weeks 4, 8, and 16; urine samples were collected at baseline and Weeks 4 and 16. Results: Of 367 patients enrolled in the study, 362 were included in the safety analysis, 351 completed study treatment, and 4 withdrew due to treatment-emergent adverse events not related to laboratory abnormalities. Bot dupilumab + TCS groups showed overall trends toward increases in mean blood levels of eosinophils and alkaline phosphatase, and decreases in mean blood levels of platelets, neutrophils, and lactate dehydrogenase levels, without corresponding mean changes in the placebo + TCS group. None of these changes were associated with symptoms or clinically meaningful adverse outcomes, and none led to treatment modification. No clinically significant changes or trends were observed for other measured laboratory parameters. Conclusion: There were no clinically meaningful adverse changes in routine laboratory parameters attributable to treatment with dupilumab + TCS. Changes in platelet counts and lactate dehydrogenase levels likely reflect reduced inflammation. These results confirm similar findings in adults and adolescents, and suggest that there is no need for routine laboratory monitoring of children aged 6 to < 12 years treated with dupilumab + TCS for severe AD
Hot-Carrier Cooling in High-Quality Graphene is Intrinsically Limited by Optical Phonons
No full textMany promising optoelectronic devices, such as broadband photodetectors, nonlinear frequency converters, and building blocks for data communication systems, exploit photoexcited charge carriers in graphene. For these systems, it is essential to understand the relaxation dynamics after photoexcitation. These dynamics contain a sub-100 femtosecond thermalization phase, which occurs through carrier-carrier scattering and leads to a carrier distribution with an elevated temperature. This is followed by a picosecond cooling phase, where different phonon systems play a role: graphene acoustic and optical phonons, and substrate phonons. Here, we address the cooling pathway of two technologically relevant systems, both consisting of high-quality graphene with a mobility >10,000 cm2V􀀀1s􀀀1 and environments that do not efficiently take up electronic heat from graphene: WSe2-encapsulated graphene and suspended graphene. We study the cooling dynamics using ultrafast pump-probe spectroscopy at room temperature. Cooling via disorder-assisted acoustic phonon scattering and out-of-plane heat transfer to substrate phonons is relatively inefficient in these systems, suggesting a cooling time of tens of picoseconds. However, we observe much faster cooling, on a timescale of a few picoseconds. We attribute this to an intrinsic cooling mechanism, where carriers in the high-energy tail of the hot-carrier distribution emit optical phonons. This creates a permanent heat sink, as carriers efficiently re-thermalize. We develop a macroscopic model that explains the observed dynamics, where cooling is eventually limited by optical-to-acoustic phonon coupling. These fundamental insights will guide the development of graphene-based optoelectronic devices
Which Promises Actually Matter?:Election Pledge Centrality and Promissory Representation
No full textParties make hundreds of campaign promises but not all are seen by voters as central to a party's offering. Studies of government promise fulfilment accept that not all promises are equivalent but in practice treat all promises equally because they lack an appropriate means of measuring promise centrality. To demonstrate the importance of accounting for pledge fulfilment, we develop a conjoint experiment method to measure public opinion about promise centrality which can be used to construct centrality weights. We demonstrate this approach’s utility by examining the 2017 UK Conservative manifesto. Centrality weighting reduces our assessment of Conservative promise-keeping by 21 percentage points (1.3 standard deviations of typical promise completion rates found in comparative studies). Weighting increases the centrality of EU promises sevenfold, immigration promises sixfold, and reduces the centrality of miscellaneous administrative promises by more than half. These results illustrate that pledge centrality cannot be ignored when assessing pledge fulfillment
Effect of Electric Field Uniformity on Breakdown Mechanisms of Dielectric Liquids under Lightning Impulse
No full textThe electric field uniformity imposes a significant effect on the breakdown mechanisms of dielectric liquids. In general, breakdown is dominated by streamer initiation under uniform field, while it is dominated by streamer propagation under non-uniform field. This paper presents a study on identifying and quantifying the transition field factor boundary, represented by the field enhancement factor ƒ, between the two dominating breakdown mechanisms. The methods for deducing the transition field factor boundary are introduced. The first method from our previous study was developed by measuring and processing both the streamer initiation and breakdown voltages. In this paper, a new method is developed by only processing the breakdown voltage data. Based on the breakdown results reproduced from the literature, the transition field factor boundaries are derived for the mineral oil under both positive and negative lightning impulses. It is found that the negative transition field factor boundary is lower than the positive one. A four-region model is proposed to describe the effect of impulse polarity on breakdown mechanisms of dielectric liquids and to interpret the transition of breakdown mechanisms with respect to the field uniformity