13506 research outputs found
Sort by
The LINC Complex: A Molecular and Biomechanical Investigation into Breast Cancer Cell Migration
Get PDFCell motility is an important feature during physiological conditions such as in development and wound healing. However, cell migration is also associated with a plethora of debilitating diseases including cancer metastasis. The LInker of the Nucleoskeleton and Cytoskeleton (LINC) complex mechanically tethers the nucleoskeleton to the cytoskeleton to enable force transmission though the nuclear envelope in response to external stimuli. A conserved interaction between Sad1-UNC- 84 (SUN) and Klarsicht, ANC-1 and SYNE/nesprin-1 and -2 Homology (KASH) proteins can be found in the heart of the LINC complex. The LINC complex is thought to govern nuclear envelope architecture and biomechanics, which can be determining factors during restrictive cell migration. Hence, shedding more light onto the role and regulation of the LINC complex could contribute towards a novel understanding of the mechanisms underlying cancer cell invasion and migration.
This project aimed to investigate variations between LINC complex composition and disulphide-dependent interactions in healthy breast epithelia compared to highly metastatic breast cancer cells. Additionally, we assessed the effects of thapsigargin- induced ER stress on LINC complex biology to find that nuclear envelope architecture, composition and chromatin organization are regulated by the LINC complex. Disruption of the conserved disulphide linkage within the SUN/KASH interaction increased directional cell migration in MDA-MB-231 cells but not in HaCaT cells, supporting the idea that different LINC complexes exist in different cell types. Lastly, we investigated the effects of pharmacological inhibition of protein disulphide isomerase (PDI) on the LINC complex. Our results suggest that PDI is unlikely to interact with the LINC complex directly, although it has important functions in promoting 2D and 3D breast cancer cell migration.
Overall, our results suggest that LINC complex conformations are cell type specific while LINC complex disruptions increase the migratory capabilities of MDA-MB-231 breast cancer cells during 2D and space-restrictive 3D migration
Designing a Fusion Power Plant with Superconducting Training Magnets
Get PDFFusion power has the potential to revolutionise global energy production with a reliable, low CO2 (not zero due to the use of steel, concrete etc. that typically produce CO2 during manufacture), low radioactivity power supply, that
is readily available at the point of need. The ITER and SPARC reactors are already under construction, with plans to begin full-power (Qfus ≥ 10) operation in the early 2030s; proving that fusion is a viable energy source. To
see wide adoption however, reactors must be made as commercially attractive as possible. Here we present superconducting pilot reactor designs that have
been optimised for minimum capital cost using the PROCESS systems code. Key design choices were made using technologies that are either available now or already in development; with concentrated effort these reactors could be built on 2030-2040 timescales. We focus primarily on the reactor from this set with the lowest overall capital cost, our “preferred” reactor: a 100 MW net electricity producing tokamak with REBCO superconducting toroidal field
coils and central solenoid and Nb-Ti superconducting poloidal field coils. In addition, we have investigated using ductile, remountable Nb-Ti training coils (named after the training wheels of children’s bicycles) during the commissioning phase of a reactor to remove the risk of brittle failure of the full-power magnets during this stage. Such magnets would operate at lower field, but would enable thorough machine testing. Finally, we investigate and predict how advances in magnet technologies could effect our preferred reactor design and cost, and conclude that the effects of such advances do not justify waiting yet longer before beginning detailed reactor design and construction
JESUS AND THE VISIBILITY OF GOD: SIGHT AND BELIEF IN THE FOURTH GOSPEL
Get PDFThis thesis establishes the value of the physical incarnation of God for belief. It asserts that the theological nature of belief derives from a God who can make himself physically visible in the world. While scholars have often debated the relationship between the empirical senses and belief in John, few have queried the presuppositions about God’s invisibility that inform their positions. In response, this thesis argues across six chapters that unless God becomes physically visible in Jesus, belief does not obtain. Chapter 1 shows that God himself is ultimately the cause, content, and consequence of the belief that John 20:30-31 describes as the purpose of the Gospel. It establishes the theological nature of belief and thus the fact that the Gospel endeavours to draw humanity close to God via faith in Jesus. The remaining five chapters argue that seeing God in Jesus is both possible and desirable. Chapter 2 re-evaluates the metaphysics of divine visibility in Early Judaism and in John and concludes that God can be physically visible in Jesus’s body. John does not regard divinity as invisible in itself; rather, he claims that seeing Jesus is seeing God. Two long chapters follow and substantiate the claims of Chapter 2. They point up the entwined nature of divine presence and material reality by arguing that Jesus’s body is a divine place. This fact – coupled with John’s depiction of Jesus as a man in divine places – stresses his divinity on earth even as it reveals his localized humanity. Chapter 5 argues that sight itself is the primary catalyst for belief in John. Although human hearts occlude proper vision, seeing remains key to human apprehension of God and belief in him. Chapter 6 draws the foregoing together by arguing that seeing Jesus is seeing God across the Johannine narratives, both despite and because of their deeply counterintuitive climax in the crucifixion
Active Temperature Control Algorithms for Improved Reliability and Lifetime of Photovoltaic Power Converters
Get PDFPower converters are exposed to environmental stresses that affect reliability. Among these, ambient temperature and solar irradiance are the ones that affect photovoltaic (PV) systems the most. For solar irradiance this is especially true for days with dynamic irradiance like those with variable cloud conditions. The power conversion is not perfect and has power losses that heat up the components. Among the most fragile components in power converters are power semiconductors and capacitors, which are greatly affected by thermal variations. This thesis presents temperature control algorithms to enhance reliability and lifetime of PV converters. The algorithms are focused on thermal control through duty cycle regulation. The first one is called temperature-controlled (TC) maximum power point tracking (MPPT) algorithm and is used for lifetime improvement of PV converters under dynamic irradiance conditions during cloudy days. The second is called maximum-temperature-limited (MTL) MPPT algorithm and is used to improve the lifetime of PV converters by limiting the output power during days with high irradiance and high ambient temperature levels. The effectiveness of the algorithms is verified using extensive simulations, evaluating the lifetime and comparing it with the energy generated. For the TC MPPT, the evaluation is done under daily irradiance profiles for different cloud conditions, while for the MTL MPPT a maximum temperature is set to test during a yearly mission profile. The results show that the TC MPPT algorithm managed to reduce life consumption by 4.68% with 0.08% of energy reduction for very variable cloud condition days. Moreover, the MTL MPPT algorithm reduced the yearly life consumption by 28.36% with a small energy generation cost of 3.97%. Based on these results it is possible to validate the effectiveness of thermal management strategies, which apart from enhancing energy production with no extra hardware cost can improve reliability at the same time
Learning from biology to design stimuli-responsive capsules
Get PDFAs well as being model cell membranes, lipid vesicles are widely used as an encapsulation technology due to their impermeable membrane. Hydrogels are similarly useful due to their biocompatibility, mechanical strength, and potential for stimulus-responsive behaviour.
By combining these two structures, the benefits of both can be reaped, giving a structure with both mechanical strength and the possibility to encapsulate actives within an impermeable membrane.
However, the interactions between the gel and membrane, and their implications, are not well understood. This thesis considers two different composite structures of lipid vesicles and hydrogels as potential systems for encapsulation and controlled release. These structures are hydrogel-embedded vesicles, and Gel-Filled Vesicles (GFVs). The hydrogel-embedded vesicles are subjected to different types of mechanical stresses. Osmotic shocks are used to apply a uniform pressure on the lipid bilayer, and compression of the hydrogel by a micromanipulator is used to cause a uni-directional force.
Agarose-embedded vesicles are shown to experience an adhesive interaction between the membrane and the gel, causing vesicle behaviours to be altered in comparison to free-floating vesicles. Of particular note is the formation of a buckled morphology for embedded vesicles subjected to hyperosmotic shocks.
Additionally, the formation of GFVs demonstrating the poration mechanism of controlled release is attempted. A suitable gel core of poly(acrylamide-co-acrylic acid) is synthesised and characterised for Upper Critical Solution Temperature behaviour.
In summary, this thesis demonstrates that interactions between the lipid bilayer and a hydrogel can strongly affect membrane behaviours, and therefore their uses for either encapsulation systems or for biophysical models
Investigating Comparisons Between Human Learning and Machine Learning Using the Dots and Boxes Game
Get PDFFrom its origins, machine learning has drawn inspiration from the human brain and its thought processes. Despite machine learning drawing so much from human learning, comparisons of the progression of learning between the two are fraught with difficulties. This study aims to explore the similarities and differences between human and machine learning, using a perfect information board game, Dots and Boxes, that both humans and machine learning agents learn to play by training against the same ‘box-greedy’ policy agent. Three q-learning reinforcement learning agents have been created with three distinct levels of strategy to compare against the learning progression and strategy of 62 human volunteers developed over 20 games each. Volunteers were also asked to complete BIS/BAS and CRT-MQC4 questionnaires after completing the Dots and Boxes task to study behavioural metrics that affect decision making, such as system 1 & 2 thinking and sensitivity to reward or punishment. Results from comparisons show how important context and prior knowledge is to human learning, and how machine learning agents can generalise better and reach optimal strategy faster with prior knowledge. Additional observations around how behavioural metrics affect individual decision making and correlations between machine learning agent strategy and human participant data allow for further comparisons to be made between human and machine learning
Charming Decays And How To Calculate Them
Get PDFIn this work we focus on the phenomenology of the charm system, more specifically the description of D-mixing and the lifetimes of the , and meson. We start with a brief introduction of flavour physics and the role the charm quark plays in the Standard Model (SM). Then, we focus on more specialised techniques like the Weak Effective Theory (WET) and the Heavy Quark Effective theory (HQET) as well as the Heavy Quark Expansion (HQE), a framework built to express inclusive decays of heavy hadrons as a series of local operators. We continue with the description of the neutral meson mixing system in general before focusing on the case and discuss the peculiarities arising that make its theoretical description more difficult than the B system. We propose two different methods of tackling these issues and show that we can get results in the ballpark of the experimental measurements. Then, we move to the calculations of the D mesons lifetimes. Including the recently calculated Darwin operator contribution and Bag parameters, we present updated results for the total and semi-leptonic decay rates and their ratios. We conclude that after comparing our results with experimental measurements by the LHCb, Belle II and BESIII collaborations we can describe inclusive decays of charm mesons in the HQE framework albeit with large theoretical uncertainties. Finally, we suggest how this work could continue in the future and what new measurements would be needed to get more precise results
Evaluating methods in Dental Anthropology to study biological affinities in Medieval Iberian Populations
Get PDFDental anthropologists have used dental morphology and measurements to infer biological relatedness among species, populations, and sometimes even family members, for nearly a century. The rapid development of new technologies in the last 15 years has resulted in sophisticated methods. These new methods have allowed us to observe teeth and dental structures which we could not study without destroying other human remains or that we could not access because they were kept at museums overseas. While many researchers have embraced the new methods, few studies have examined what they bring to dental anthropology, whether they improve on traditional methods, and when it is best to use them. I compared four methods to estimate biological relatedness in terms of the information they yield, their reliability, and the ease of application: metric variables, nonmetric dental traits included in the Arizona State University system, and 2-Dimensional and 3-Dimensional geometric morphometrics. To make this comparison, I used three archaeological medieval samples from different cultural contexts (one Christian and two Muslim) in the Iberian Peninsula. I aimed to infer whether there are biological differences among the samples and if so, which samples are biologically closer to one another. I chose these samples because traditionally, historians have thought that the Muslim entry to the Iberian Peninsula occurred in very low numbers and that the vast majority of Muslims that lived in the Iberian Peninsula during the Middle Ages were local people converted to Islam, so I tested if this was observed when comparing samples with different cultural backgrounds. Of the four methods, 2-Dimensional geometric morphometrics and nonmetric dental traits found the most significant differences between populations. These significant differences were between the Christian and the Muslim samples, although one of the Muslim samples, whose cultural background was Christian, was geographically closer to the Christian sample. The fact that there are significant differences between the Muslim and the Christian samples suggests that the Islamic arrival to the Iberian Peninsula was made in larger numbers than it was thought, even if there was an admixture with the local population. I also found that 3-Dimensional geometric morphometrics was difficult to apply, more time-consuming, and provided results that were not consistent with the results obtained with the other methods. The results of 3-Dimensional geometric morphometrics could have improved if used in the enamel-dentine junction of CT-scans of the teeth, but that requires a great deal of money, time, and skills. Researchers aiming to study the biological relatedness of archaeological samples should choose their methods taking into account the samples used, their degree of expertise, and their availability of resources if they want to avoid results that do not necessarily reflect such relatedness
Developing a Comprehensive Quality Model in Higher Education: Medical Employers’ Perspective
Get PDFIn higher education, quality management has been introduced to regulate the overall performance of institutions. In Saudi Arabia, less than 50% of employers believe that educational systems succeed in preparing students for the marketplace (Collet, Hine, & Plessis, 2015; Damoah, Peprah, & Brefo, 2021; Gallagher, 2015). This lack of preparedness may have resulted in poor employment rates, particularly among medical graduates. In order to reduce unemployment among medical graduates, employers need to be involved in developing a holistic understanding of these issues and a subsequent quality model of medical education that is relevant to the labor market so that it closes the gap between higher education and the medical labor market. The aim of this study is to gain insights into how medical employers conceptualize quality in higher education. The objective is to develop a model of the quality of medical education at Saudi universities from the perspective of employers. The resulting model will take account of both the attributes of medical graduates and the universities themselves.
The study utilizes an exploratory two-stage design: semi-structured interviews followed by a survey. Interviews were carried out with 14 employers from six hospitals. The survey sample size is 251 respondents. The resulting quality model consists of seven dimensions, namely: 1) Educational Experience, 2) Medical Training, 3) Scientific Research, 4) University Reputation, 5) Pedagogic Quality, 6) Administrative Quality and 7) Graduate Quality. Additionally, the findings show that employers value eight soft skills in medical graduates: commitment to work, communication, decision making, continuous learning, confidence, ability to work under pressure, time management, and self-improvement skills.
This model will create enhancement opportunities for medical education to overcome the deficiencies that lead to less competent graduates and it has the potential to enhance the higher education system
Time is TikToking: User perceptions of primate videos on one of the fastest growing social media platforms
Get PDFIntroduction: With billions of social media users, platforms have a powerful influence on user
perceptions of and behaviour toward wild animals. TikTok is known for its large and young
user base <-30 years old and focus on entertainment, but we currently have no knowledge of
what primate content is posted, its popularity, and whether video characteristics negatively
influence user perceptions of primates.
Methods: A pilot study showed that searching for ‘monkey’ resulted in videos of monkeys,
apes and strepsirrhines. I collected data on the number of hearts, views and account followers,
video and account types, comment and video activity themes, genus, primate infant and
human presence, human-primate proximity, primates in clothes, presence of pet primates and
domestic pets, human-primate behaviour, video setting, context, and barrier presence from
1104 videos, using the search terms ‘monkey’ (n= 759) and ‘zoo monkey’ (n= 345).
Results: Primate videos received millions of views and hearts, indicating that they are very
popular. Almost all videos were entertainment focused. Setting (zoo vs. non-zoo) had a
significant effect on video popularity, suggesting that primates in zoos were least enjoyable to
watch compared to in non-zoo settings. Zoo primates provoked significantly fewer comments
about wanting a primate pet than in non-zoo settings, suggesting that zoos make them appear
more dangerous than non-zoo settings. When videos included written context promoting
primate pet-keeping, users were significantly more interested in pet primates than videos
without this context. Direct human-primate contact resulted in significantly more users
wanting pet primates than videos showing humans within arm’s reach of primates, but not
touching them. Videos including infants received significantly more comments referring to
‘cuteness’ and comments expressing a desire for a pet primate than videos without infants
did.
Discussion: To minimise the negative effects on user perceptions of primates, TikTok
uploaders should educate users in written format and avoid posts featuring primate infants
and direct human-primate contact. I propose a ‘positive input - positive output’ hypothesis,
which addresses how posting entertaining conservation videos could increase content
popularity and public awareness and thus improve pro-conservation behaviours by users
online
Data sources:
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇