8383 research outputs found
Sort by
XMU-MP-1 induces growth arrest in a model human mini-organ and antagonises cell cycle-dependent paclitaxel cytotoxicity
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: received 2020-05-22, registration 2020-09-03, accepted 2020-09-03, pub-electronic 2020-09-17, online 2020-09-17, collection 2020-12Publication status: PublishedFunder: Manchester Biomedical Research Centre; doi: http://dx.doi.org/10.13039/100014653Abstract: Background: XMU-MP-1 is an inhibitor of the Hippo pathway kinases MST1/2 and has been shown to promote the downstream activation of the pro-proliferative, pro-regenerative and anti-apoptotic transcriptional regulator YAP1. We tested whether XMU-MP-1 can activate YAP1 in a model human mini-organ, namely the hair follicle, to determine whether it can be pharmacologically exploited to promote regeneration in the hair follicle as a novel strategy to treat pathological hair loss disorders. Results: XMU-MP-1 treatment inhibited MOB1 phosphorylation but did not increase active YAP1 in the hair follicle. Rather than promote proliferation, XMU-MP-1 serendipitously decreased the number of Ki-67+, EdU+ and phospho histone H3+ hair matrix keratinocytes and antagonised the cytotoxic effects of paclitaxel. Conclusions: XMU-MP-1 perturbs epithelial cell cycle progression in a model human mini-organ. This may arise as an off-target effect, especially when XMU-MP-1 has been described to strongly inhibit 21 additional kinases beyond MST1/2. Therefore, whilst these effects may be dependent on tissue context, researchers should exercise caution when interpreting the effects of XMU-MP-1, especially in tissues with actively proliferating cell populations
Suprachiasmatic nucleus-dependent and independent outputs driving rhythmic activity in hypothalamic and thalamic neurons
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: received 2020-05-29, registration 2020-09-17, accepted 2020-09-17, pub-electronic 2020-09-30, online 2020-09-30, collection 2020-12Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/N007115/1Abstract: Background: Daily variations in mammalian physiology are under control of a central clock in the suprachiasmatic nucleus (SCN). SCN timing signals are essential for coordinating cellular clocks and associated circadian variations in cell and tissue function across the body; however, direct SCN projections primarily target a restricted set of hypothalamic and thalamic nuclei involved in physiological and behavioural control. The role of the SCN in driving rhythmic activity in these targets remains largely unclear. Here, we address this issue via multielectrode recording and manipulations of SCN output in adult mouse brain slices. Results: Electrical stimulation identifies cells across the midline hypothalamus and ventral thalamus that receive inhibitory input from the SCN and/or excitatory input from the retina. Optogenetic manipulations confirm that SCN outputs arise from both VIP and, more frequently, non-VIP expressing cells and that both SCN and retinal projections almost exclusively target GABAergic downstream neurons. The majority of midline hypothalamic and ventral thalamic neurons exhibit circadian variation in firing and those receiving inhibitory SCN projections consistently exhibit peak activity during epochs when SCN output is low. Physical removal of the SCN confirms that neuronal rhythms in ~ 20% of the recorded neurons rely on central clock input but also reveals many neurons that can express circadian variation in firing independent of any SCN input. Conclusions: We identify cell populations across the midline hypothalamus and ventral thalamus exhibiting SCN-dependent and independent rhythms in neural activity, providing new insight into the mechanisms by which the circadian system generates daily physiological rhythms
The bodily-attitudinal theory of emotion
Get PDFFrom Springer Nature via Jisc Publications RouterHistory: accepted 2020-09-30, registration 2020-10-01, online 2020-10-10, pub-electronic 2020-10-10, pub-print 2021-08Publication status: PublishedFunder: British Academy; Grant(s): 180024Funder: University of ManchesterAbstract: This paper provides an assessment of the bodily-attitudinal theory of emotions, according to which emotions are felt bodily attitudes of action readiness. After providing a reconstruction of the view and clarifying its central commitments two objections are considered (absence of bodily phenomenology and what kind of bodily awareness). An alternative object side interpretation of felt action readiness is then provided, which undermines the motivation for the bodily-attitudinal theory and creates problems for its claims concerning the content of emotional experience. The conclusion is that while the bodily-attitudinal theory marks out a distinctive proposal concerning the question of what emotions are, there remain significant issues which need addressing if it is to be a plausible competitor to existing theories of emotion
Numerical methods for deterministic and stochastic fractional partial differential equations
Get PDFIn this thesis we will explore the numerical methods for solving deterministic and stochastic space and time fractional partial differential equations. Firstly we consider Fourier spectral methods for solving some linear stochastic space fractional partial differential equations perturbed by space-time white noises in one dimensional case. The space fractional derivative is defined by using the eigenvalues and eigenfunctions of Laplacian subject to some boundary conditions. We approximate the space-time white noise by using piecewise constant functions and obtain the approximated stochastic space fractional partial differential equations. The approximated stochastic space fractional partial differential equations are then solved by using Fourier spectral methods.
Secondly we consider Fourier spectral methods for solving stochastic space fractional partial differential equation driven by special additive noises in one dimensional case. The space fractional derivative is defined by using the eigenvalues and eigenfunctions of Laplacian subject to some boundary conditions. The space-time noise is approximated by the piecewise constant functions in the time direction and by appropriate approximations in the space direction. The approximated stochastic space fractional partial differential equation is then solved by using Fourier spectral methods.
Thirdly, we will consider the discontinuous Galerkin time stepping methods for solving the linear space fractional partial differential equations. The space fractional derivatives are defined by using Riesz fractional derivative. The space variable is discretized by means of a Galerkin finite element method and the time variable is discretized by the discontinous Galerkin method. The approximate solution will be sought as a piecewise polynomial function in t of degree at most q−1, q ≥ 1, which is not necessarily continuous at the nodes of the defining partition. The error estimates in the fully discrete case are obtained and the numerical examples are given.
Finally, we consider error estimates for the modified L1 scheme for solving time fractional partial differential equation. Jin et al. (2016, An analysis of the L1 scheme for the subdiffifusion equation with nonsmooth data, IMA J. of Number. Anal., 36, 197-221)
ii established the O(k) convergence rate for the L1 scheme for both smooth and nonsmooth initial data. We introduce a modified L1 scheme and prove that the convergence rate is O(k2−α=), 0 < α < 1 for both smooth and nonsmooth initial data. We first write the time fractional partial differential equations as a Volterra integral equation which is then approximated by using the convolution quadrature with some special generating functions. A Laplace transform method is used to prove the error estimates for the homogeneous time fractional partial differential equation for both smooth and nonsmooth data. Numerical examples are given to show that the numerical results are consistent with the theoretical results
Creative Practices for Wellbeing - Practice Guidance
Get PDFThis item has been translated into various languages: English - http://dx.doi.org/10.13140/RG.2.2.11610.90567/1; Welsh - http://dx.doi.org/10.13140/RG.2.2.23512.24322/1; Albanian - http://dx.doi.org/10.13140/RG.2.2.13288.62727/1; Bulgarian - http://dx.doi.org/10.13140/RG.2.2.19999.51364; Chinese (simplified) - http://dx.doi.org/10.13140/RG.2.2.30065.84325 ; Chinese (traditional) - http://dx.doi.org/10.13140/RG.2.2.36776.72963; Danish - http://dx.doi.org/10.13140/RG.2.2.16801.35688; French - http://dx.doi.org/10.13140/RG.2.2.33578.57288/1; Greek - http://dx.doi.org/10.13140/RG.2.2.11768.19201; Icelandic - http://dx.doi.org/10.13140/RG.2.2.20667.16161; Lithuanian - http://dx.doi.org/10.13140/RG.2.2.25189.96484/1; Russian - http://dx.doi.org/10.13140/RG.2.2.31900.85127; Spanish - http://dx.doi.org/10.13140/RG.2.2.13445.91360; Swedish - http://dx.doi.org/10.13140/RG.2.2.10929.33126; Vietnamese - http://dx.doi.org/10.13140/RG.2.2.24351.10406;
Polish - http://dx.doi.org/10.13140/RG.2.2.17407.15524
Sinhala - http://dx.doi.org/10.13140/RG.2.2.20762.59843Using creativity for wellbeing has grown significantly over the years and is now becoming commonplace in many different contexts and settings, such as classrooms, workplaces, hospitals, hospices, community spaces, festivals, and even government.
Evidence for the use of creative practices such as poetry, storytelling, or biographical writing to support recovery or promote personal development is long established and is growing, and demonstrates an incredible power and potential.
Amidst this setting, and with the support of TS Eliot Foundation, The Old Possum’s Practical Trust, and the University of Chester, this guidance was developed to support practitioners in delivering effective and safe practice
Pictures, Colors and Emotions: Shaping the UK's E-Tourism Experience
No full textThe role of online media has become more important for tourism as DMOs try to differentiate through the use of pictures on digital channels, such as websites. The aim is to provide a positive image that has a positive impact on the consumer buying decision. Pictures draw significant amounts of attention and a pictures colour characteristics are critical in maintaining interest through emotional connections. These colour characteristics concern hue, saturation and luminance, which create a positive or negative emotional response in the prospective user.
Due to this importance of a pictures colour characteristics on websites, this chapter explores these colour characteristics of pictures on UK DMO websites, in order to determine the positive or negative emotions conveyed to the viewer. Results show that most pictures are neutral but the amount of negatively perceived pictures is very high. It was found that the overall visual e-tourism experience can be improved with only small post-processing changes with minimal danger of distorting reality
Modelling impact damage in composite laminates: A simulation of intra- and inter-laminar cracking
No full textIn this work, stress- and fracture mechanics-based criteria are developed to predict initiation and evolution, respectively, of intra- and inter-laminar cracking developed in composite laminates subjected to a relatively low energy impact (⩽15 J) with consideration of nonlinear shear behaviour. The damage model was implemented in the finite element (FE) code (Abaqus/Explicit) through a user-defined material subroutine (VUMAT). Delamination (or inter-laminar cracking) was modelled using interface cohesive elements while splitting and transverse matrix cracks (intralaminar cracking) that appeared within individual plies were also simulated by inserting cohesive elements along the fibre direction (at a crack spacing determined from experiments for computing efficiency). A good agreement is obtained when the numerically predicted results are compared to both experimentally obtained curves of impact force and absorbed energy versus time and X-ray radiography damage images, provided the interface element stiffness is carefully selected. This gives confidence to selected fracture criteria and assists to identify material fracture parameters that influence damage resistance of modern composite material systems
Globalization and International Students: Re-modelling Micro-international Aspects for the Entrepreneurial University
No full textIn the highly competitive higher education (HE) market for international students, the adoption of entrepreneurial approaches to internationalization by universities and higher education institutions (HEIs) is imperative in order to ensure a sustainable organizational future. Due to program popularity, HEI business schools often find themselves at the forefront of internationalization. While an appreciation of the need for ‘entrepreneurial’ behavior with regards to macro-aspects of internationalization (for example, international recruitment and market development) is longstanding, a developed understanding of, and the extension of ‘entrepreneurial’ approaches into the micro-contexts (i.e. student experience in the classroom setting) remains surprisingly understudied, particularly at the micro-operational level. This chapter adopts an inductive case study approach, focusing on a HEI business school undergraduate cohort in the United Kingdom (UK). The study collected data via semi-structured interviews, focus groups and questionnaires conducted with students and academic staff involved in internationalization. Overall, the study generates a micro-portrayal of the issues faced by a UK HEI business school as it attempts to develop ‘entrepreneurial’ approaches to, and models for, its internationalization strategy. Specifically, the chapter develops insights into the challenges associated with student experience and linguistic engagement, program design and delivery and highlights areas of potential development. These findings and their implications enable HEI business schools to rethink and remodel ways in which issues originating in macro-aspects of internationalization can be successfully addressed at the micro-level
In Darwin’s Garden: an evolutionary exploration of augmented reality in practice
Get PDFThis book is part of the Springer Advanced Information and Knowledge Processing Series and will be published under Springer's Open Access policy.This chapter discusses the rapid developments in augmented reality and mixed reality technologies, from a practitioner’s perspective of making the augmented reality sculptural work In Darwin’s Garden. From its conception in 2012, to its exhibition at Carbon Meets Silicon II in 2017, the advances in augmented reality technology led to an interplay between the goal of the creators and the technological realisation of that vision. The art, design and technology involved, generated a reactive process that was mired in external influences as the accessibility to augmented reality became commercially valuable and subsequently restricted. This chapter will be of interest to anyone who wants to understand more about the possibilities, technologies and processes involved in realising mixed reality practice and about the commercial culture that supports it
A wordbook of rare mithers: Swaddledidaff
No full textA quarterly column exploring Cheshire and its dialec
Data sources:
Access Repository Dashboard
Do you manage ChesterRep? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!