69 research outputs found
Christianity and Communication: Kierkegaard, Hamann, and the Necessity of Indirect Communication
In 1849, Kierkegaard praised Hamann\u27s dedication to written and spoken language as derived from the Divine Logos. This thesis examines Hamann and Kierkegaard in order to understand both thinkers\u27 impact upon verbal and written communication. Hamann\u27s dedication to the idea of communication as given graciously and solely by God is apparent in his authorship. Kierkegaard\u27s model of indirect communication is ultimately one of Christian existence. Given the fact that Kierkegaard owed much to Hamann and was perhaps even led back to faith in God through his exhaustive reading of the German linguist, this thesis examines the possibility of a Hamannian impact upon Kierkegaard\u27s conception of communication. The research question throughout this thesis is: What is Hamann\u27s influence upon Kierkegaard\u27s theory of indirect communication
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Investigating and exploiting the latency-associated expression of the human cytomegalovirus gene US28 in early myeloid lineage cells.
Human cytomegalovirus (HCMV) is a betaherpesvirus which establishes a lifelong persistent infection, underpinned by its ability to establish latent infection in early myeloid lineage cells, in the infected host. Although well controlled by a healthy immune system, HCMV causes pathological and life threatening disease in individuals with a compromised or immature immune response, which can come from primary HCMV infection or reactivation of latent infection. Although progress is being made in understanding the mechanisms by which HCMV maintains latency and reactivates, a better understanding is essential towards the aim of targeting and killing latently infected cells.
In this thesis, I will present evidence that the HCMV-encoded chemokine receptor homologue US28, which is expressed during latent infection of CD14+ monocytes, is necessary for maintaining HCMV latency in these monocytes and, in the absence of US28 protein expression, HCMV undergoes lytic infection. US28 expression was found to attenuate cellular signalling pathways in latently infected cells; in particular, MAP kinase and NFÎşB. Interestingly, deletion of the US28 gene or inhibition of the US28 protein resulted in the expression of lytic antigens which allowed detection of infected monocytes by the immune system. This observation may lead to a potential new immunotherapeutic strategy against latent HCMV.
Having demonstrated that US28 protein is expressed on the surface of latently infected monocytes, I tested whether a new fusion-toxin protein, called F49A-FTP, which binds US28 protein, could be used to target and kill latently infected cells. I developed a protocol for treating latently infected monocytes with F49A-FTP which resulted in a significant reduction in virus reactivation after monocyte differentiation to dendritic cells. I was also able to show that this treatment kills CD34+ progenitor cells, which were experimentally latently infected with HCMV, as well as latently infected monocytes from a healthy, seropositive blood donor.
Finally, during my investigations into the role of US28 during HCMV latency, a mass spectrometry screen was performed to measure changes in cellular protein expression when US28 protein is expressed in isolation, in THP-1 monocyte-like cell line. This identified CTCF, a transcription factor which appears to be modified by US28 in THP-1 cells. I showed that CTCF has a repressive effect on the HCMV MIEP, and that CTCF likely plays a role in HCMV latency.
In summary, this work provides insights into the role of US28 during HCMV latency, and proposes potential novel therapeutic strategies to kill latently infected cells.My PhD was funded by the Wellcome Trust, while my lab was funded by the Medical Research Council
Spontaneous Jamming in One-Dimensional Systems
We study the phenomenon of jamming in driven diffusive systems. We introduce
a simple microscopic model in which jamming of a conserved driven species is
mediated by the presence of a non-conserved quantity, causing an effective long
range interaction of the driven species. We study the model analytically and
numerically, providing strong evidence that jamming occurs; however, this
proceeds via a strict phase transition (with spontaneous symmetry breaking)
only in a prescribed limit. Outside this limit, the nearby transition
(characterised by an essential singularity) induces sharp crossovers and
transient coarsening phenomena. We discuss the relevance of the model to two
physical situations: the clustering of buses, and the clogging of a suspension
forced along a pipe.Comment: 8 pages, 4 figures, uses epsfig. Submitted to Europhysics Letter
Assistive Smart Cane (ASCane) for fall detection: first advances
The development of fall detection systems with the capability of real-time monitoring is necessary considering that a large amount of people die and suffer severe consequences from falls. Due to their advantages, daily life accessories can be a solution to embed fall-related systems, and canes are no exception. In this paper, it is presented a cane with fall detection abilities. The ASCane is instrumented with an inertial sensor which data will be tested with three different fixed multi-threshold fall detection algorithms, one dynamic multi-threshold and machine learning methods from the literature. They were tested and modified to account the use of a cane. The best performance resulted in a sensitivity and specificity of 96.90% and 98.98%, respectively.This work is supported by the FCT - Fundação para a Ciência e Tecnologia - with the scholarship reference PD/BD/141515/2018, with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 - Programa Operacional Competitividade e Internacionalização (POCI) - with the reference project POCI-01-0145-FEDER-006941
Jamming transition in a homogeneous one-dimensional system: the Bus Route Model
We present a driven diffusive model which we call the Bus Route Model. The
model is defined on a one-dimensional lattice, with each lattice site having
two binary variables, one of which is conserved (``buses'') and one of which is
non-conserved (``passengers''). The buses are driven in a preferred direction
and are slowed down by the presence of passengers who arrive with rate lambda.
We study the model by simulation, heuristic argument and a mean-field theory.
All these approaches provide strong evidence of a transition between an
inhomogeneous ``jammed'' phase (where the buses bunch together) and a
homogeneous phase as the bus density is increased. However, we argue that a
strict phase transition is present only in the limit lambda -> 0. For small
lambda, we argue that the transition is replaced by an abrupt crossover which
is exponentially sharp in 1/lambda. We also study the coarsening of gaps
between buses in the jammed regime. An alternative interpretation of the model
is given in which the spaces between ``buses'' and the buses themselves are
interchanged. This describes a system of particles whose mobility decreases the
longer they have been stationary and could provide a model for, say, the flow
of a gelling or sticky material along a pipe.Comment: 17 pages Revtex, 20 figures, submitted to Phys. Rev.
Crystallinity Effects in Sequentially Processed and Blend-Cast Bulk-Heterojunction Polymer/Fullerene Photovoltaics
Although most polymer/fullerene-based solar cells are cast from a blend of the components in solution, it is also possible to sequentially process the polymer and fullerene layers from quasi-orthogonal solvents. Sequential processing (SqP) not only produces photovoltaic devices with efficiencies comparable to the more traditional bulk heterojunction (BHJ) solar cells produced by blend casting (BC) but also offers the advantage that the polymer and fullerene layers can be optimized separately. In this paper, we explore the morphology produced when sequentially processing polymer/fullerene solar cells and compare it to the BC morphology. We find that increasing polymer regioregularity leads to the opposite effect in SqP and BC BHJ solar cells. We start by constructing a series of SqP and BC solar cells using different types of poly(3-hexylthiophene) (P3HT) that vary in regioregulary and polydispersity combined with [6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM). We use grazing incidence wide-angle X-ray scattering to demonstrate how strongly changes in the P3HT and PCBM crystallinity upon thermal annealing of SqP and BC BHJ films depend on polymer regioregularity. For SqP devices, low regioregularity P3HT films that possess more amorphous regions allow for more PCBM crystallite growth and thus show better photovoltaic device efficiency. On the other hand, highly regioregular P3HT leads to a more favorable morphology and better device efficiency for BC BHJ films. Comparing the photovoltaic performance and structural characterization indicates that the mechanisms controlling morphology in the active layers are fundamentally different for BHJs formed via SqP and BC. Most importantly, we find that nanoscale morphology in both SqP and BC BHJs can be systematically controlled by tuning the amorphous fraction of polymer in the active layer. © 2014 American Chemical Society
A New Method of Dealing with the Peripheral Branches of the Fifth Cranial Nerve in Tic Douloureux
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Out of Time: Accomplices in Post-Carceral World-Building
An article in which a faculty member, a university staff member and former student, and a currently incarcerated student and teaching assistant collaboratively examine their experiences as co-teachers and co-learners in a humanities-based prison classroom, and as co-authors of the article itself. Fostered by the faculty member’s pedagogical approach and design of the course, the authors pose that critical practices of writing and learning are dynamic sites of imagination and collaboration, and in turn, avenues by which informed and intentional futures can be enacted. Locating their practice and experience of partnership within a prison, the authors enter their co-created and individual narratives into a discussion of the liberatory potentiality of written and collaborative “world-building” to identify, resist, and replace mechanisms of harm and oppression, effectively bringing a post-carceral world into being
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