675 research outputs found
The Accuracy of Subhalo Detection
With the ever increasing resolution of N-body simulations, accurate subhalo
detection is becoming essential in the study of the formation of structure, the
production of merger trees and the seeding of semi-analytic models. To
investigate the state of halo finders, we compare two different approaches to
detecting subhaloes; the first based on overdensities in a halo and the second
being adaptive mesh refinement. A set of stable mock NFW dark matter haloes
were produced and a subhalo was placed at different radii within a larger halo.
SUBFIND (a Friends-of-Friends based finder) and AHF (an adaptive mesh based
finder) were employed to recover the subhalo. As expected, we found that the
mass of the subhalo recovered by SUBFIND has a strong dependence on the radial
position and that neither halo finder can accurately recover the subhalo when
it is very near the centre of the halo. This radial dependence is shown to be
related to the subhalo being truncated by the background density of the halo
and originates due to the subhalo being defined as an overdensity. If the
subhalo size is instead determined using the peak of the circular velocity
profile, a much more stable value is recovered. The downside to this is that
the maximum circular velocity is a poor measure of stripping and is affected by
resolution. For future halo finders to recover all the particles in a subhalo,
a search of phase space will need to be introduced.Comment: 9 pages, 7 figures, accepted for publication in MNRA
Survey evidence: the EU referendum had a clear positive impact on young people’s political engagement
The UK’s EU referendum was often discussed in terms of a generational divide between older citizens who were more likely to vote Leave, and younger citizens who were more likely to back Remain. But did the referendum do anything to increase the interest of younger citizens in politics? Presenting survey evidence gathered at the beginning and end of the campaign, Stuart Fox and Sioned Pearce write that there are some clear indications the referendum increased engagement among young voters, but it remains an open question as to whether this interest in politics will be maintained long-term
The Role of Neutrophil Elastase in Abdominal Aortic Aneurysm and Aortic Dissection.
PhD ThesisBackground:
Abdominal Aortic Aneurysm (AAA) affects 4-5% of men over 65, and Aortic
Dissection (AD) is a life-threatening aortic pathology where 75% of patients die within
2-weeks post-onset. Relatively little is known about the underlying mechanisms, which
warrants further investigation. Neutrophil Elastase (NE) is an enzyme with roles in
priming of the immune system, clearance of large pathogens and remodelling of
extracellular-matrix proteins, all influential in AAA and AD. The Angiotensin II (Ang
II) and Calcium Chloride (CaCL2) procedures provide methods to model the AAA
pathology within small rodents, which enables the study of the disease. Furthermore,
the β-aminopropionitrile monofumarate (BAPN) model provides an animal model
which mimics the AD pathology and allows in-depth study of both changes in mortality
and pathological severity.
Within AAA and AD, there is known to be a large immune system implication in the
production and development of both pathologies, with enzymatic activity seemingly
pivotal in the initiation of the AD and AAA phenotype. With the impact of enzymes
such as immune cell-derived matrix metalloproteinases (MMPs)-2 and -9 studied in
depth. Neutrophil Elastase (NE) is an, as yet, unstudied enzyme within these processes.
Purpose:
Current treatment regimen for AAA and AD both have significant flaws and is entirely
surgical, with most at-risk groups being elderly and treatment consequentially of
increased risk of complications. Surgical intervention has complex post-operative care
considerations, with reintervention and morbidity being high within the following
weeks after the procedures take place. Understanding of the underlying mechanisms
contributing to AAA and AD is poor and therefore designing a pharmacological agent
to improve therapy is difficult. Understanding the role of NE and its implications within
AAA will allow us to identify whether it has an impact within the pathology and, if so
if it is an appropriate target for therapeutic intervention.
Therefore, the primary aims of this project was to identify if Neutrophil Elastase is
involved within the AAA and AD processes, to detect via what mechanism it may act
and if NE is a potential novel drugs target for treatment of AAA and AD.
Methods and Results:
To study if NE gene expression is regulated by AAA pathologies, in Vitro experiments
were conducted with multiple cell lines (human aortic SMCs, Raw264.7 macrophages
and HuVECs). Data from RT-qPCR analysis was insignificant and failed to show a
relation between NE, MMP2 and MMP9, when cells were treated with Angiotensin II
(Ang II) and Calcium Chloride, respectively.
Development of an MRI scanning technique to monitor the progression of AAA
overtime was undertaken. A semi-automatic methodology was developed with
representative and highly reproducible results achieved. This enabled the detailed study
of animals whilst undergoing AAA-induction procedures, namely the CaCl2 and Ang
II animal models.
By utilising two in vivo models, so far we have observed a significant difference that
the two Aneurysm models result in lower AAA incidence within NE deficient mice,
with infrarenal aortic expansion significantly reduced. Investigations into flow and
other dynamic aspects of the vessel differ between animal models and consequentially
need to be furthered but at present no significant differences were observable.
Underlying mechanisms for AAA and NEs contribution towards the pathology were
assessed, with novel associations between NE and MMPs identified as well as the
involvement of proteins such as TBL1x, Caveolin-2 and COPS8 following proteomics
analysis techniques.
Similar results were seen within AD experimentation, with knockout of NE resulting
in significantly lower mortality and vessel dissection rate. Similar histological staining
patterns were observed within this model when compared to the two AAA animal
models. This suggests a potential common pathway between the two that results in
aortic medial degradation, and rupture of the vessel.
Early Human translational experiments were carried out with a AAA patient audit, there
were no significant findings that correlated any basic blood profile characteristic to size
or progression of AAA. This work was continued, working with Barts BioBank
Resource to obtain tissues from surgical repair patients. Diseased tissues displayed
expression of NE with small areas of staining being seen alongside MMPs, such as
within the remodelled medial portion of the vessel, similar to that of previous mouse
works. Furthermore, blood serum samples from patients had no significant change in
level of NE when compared to Healthy Controls.
Conclusion:
This study identifies NE as having potential therapeutic applications if similar results
are seen within pharmacological inhibition of the enzyme as were produced as a result
of genetic knockout in mouse studies, especially within AD models. Early Translational
experimental results have not been as promising, but more work is needed to fully
understand whether NE could play a similar role within the Human condition and
therefore warrant further study as a potential drugs target, although current results need
to be developed prior to this.
Wider Implications:
Findings outlined within this thesis suggest NE has a potential role within both AD and
AAA pathologies, with implications in the regulation of MMPs as well as potential
direct enzymatic action within the modification of extracellular matrix proteins
regulated within the AAA and AD conditions. Results so far show areas of promise,
and with further investigation, NE inhibition could be established as a therapeutic
option for AAA and/ or AD. In order to establish the link further, there is a need to
determine if pharmacological knockdown of NE can produce the same results as those
seen within in vivo experiments where genetic knockout was established
Labouring under a delusion? Scotland's national questions and the crisis of the Scottish Labour Party
n recent years, the Scottish Labour Party has lost its once dominant position in Scottish politics. Its support has collapsed, and it now faces multiple political challenges, relating both to cleavages in Scottish politics over the constitution and Brexit, and to divisions within the party over its leadership and direction. Employing semi-structured elite interviews with key figures within the party hierarchy and focus groups with grassroots activists, this paper examines the causes of this crisis through an analysis of party members’ views. It identifies sources of the decline of Scottish Labour in unresolved disagreements over strategy and identity. Unable to coalesce around a distinctly Scottish strategy for competing in a multidimensional, multilevel political space with both civic nationalist challengers and conservative defenders of the constitutional status quo, in 2017, Scottish Labour reasserted a class-based identity, seeking to compete largely on the left–right economic dimension of politics. Instead of marking out a Scottish political identity, the Scottish Labour Party chose leftward national alignment with the Jeremy Corbyn leadership of the UK Labour Party. The electoral and political failure of this strategy offers important lessons for understanding the prospects of multilevel social-democratic parties
Coastal Trapped Waves Generated By Hurricane Andrew on the Texas-Louisiana Shelf
The Texas-Louisiana Shelf Circulation and Transport Study featured moorings that covered the shelf during 1992 to 1994, and captured the oceanic response on the shelf to category 4 Hurricane Andrew in August of 1992. Eighty-one current meters distributed over 31 moorings along several contours of isobaths provided excellent spatial and temporal coverage over the shelf. The low-frequency variability (2 days and longer) of current observations and tide gauges to the West of the storm are analyzed after the passage of Andrew, focusing on the region outside of direct hurricane forcing. Wavelet analyses are utilized to investigate the dominant periods excited by the storm over the shelf and their temporal evolution after forcing has subsided. Subsequent to the storm's passage, the observations and wavelet transforms show a two-to-four day period coastal trapped wave that propagate westward at speeds near 6 m/s and then around the Texas bend along the bathymetry. The signal remains detectable in observations as far south as Port Isabel, Texas. The prominent frequencies determined from wavelet analysis are compared with predicted coastal trapped wave dispersion modes and show good agreement in the predicted group speed and cross-shelf structure of the first mode. The energies calculated from the data indicate a largely barotropic shelf wave response which is corroborated in the observed currents and by theory
Streams Going Notts: The tidal debris finder comparison project
While various codes exist to systematically and robustly find haloes and
subhaloes in cosmological simulations (Knebe et al., 2011, Onions et al.,
2012), this is the first work to introduce and rigorously test codes that find
tidal debris (streams and other unbound substructure) in fully cosmological
simulations of structure formation. We use one tracking and three non-tracking
codes to identify substructure (bound and unbound) in a Milky Way type
simulation from the Aquarius suite (Springel et al., 2008) and post-process
their output with a common pipeline to determine the properties of these
substructures in a uniform way. By using output from a fully cosmological
simulation, we also take a step beyond previous studies of tidal debris that
have used simple toy models. We find that both tracking and non-tracking codes
agree well on the identification of subhaloes and more importantly, the {\em
unbound tidal features} associated with them. The distributions of basic
properties of the total substructure distribution (mass, velocity dispersion,
position) are recovered with a scatter of . Using the tracking code as
our reference, we show that the non-tracking codes identify complex tidal
debris with purities of . Analysing the results of the substructure
finders, we find that the general distribution of {\em substructures} differ
significantly from the distribution of bound {\em subhaloes}. Most importantly,
both bound and unbound {\em substructures} together constitute of the
host halo mass, which is a factor of higher than the fraction in
self-bound {\em subhaloes}. However, this result is restricted by the remaining
challenge to cleanly define when an unbound structure has become part of the
host halo. Nevertheless, the more general substructure distribution provides a
more complete picture of a halo's accretion history.Comment: 19 pages, 12 figures, accepted for publication in MNRA
Galaxies going MAD: The Galaxy-Finder Comparison Project
With the ever increasing size and complexity of fully self-consistent
simulations of galaxy formation within the framework of the cosmic web, the
demands upon object finders for these simulations has simultaneously grown. To
this extent we initiated the Halo Finder Comparison Project that gathered
together all the experts in the field and has so far led to two comparison
papers, one for dark matter field haloes (Knebe et al. 2011), and one for dark
matter subhaloes (Onions et al. 2012). However, as state-of-the-art simulation
codes are perfectly capable of not only following the formation and evolution
of dark matter but also account for baryonic physics (e.g. hydrodynamics, star
formation, feedback) object finders should also be capable of taking these
additional processes into consideration. Here we report on a comparison of
codes as applied to the Constrained Local UniversE Simulation (CLUES) of the
formation of the Local Group which incorporates much of the physics relevant
for galaxy formation. We compare both the properties of the three main galaxies
in the simulation (representing the MW, M31, and M33) as well as their
satellite populations for a variety of halo finders ranging from phase-space to
velocity-space to spherical overdensity based codes, including also a mere
baryonic object finder. We obtain agreement amongst codes comparable to (if not
better than) our previous comparisons, at least for the total, dark, and
stellar components of the objects. However, the diffuse gas content of the
haloes shows great disparity, especially for low-mass satellite galaxies. This
is primarily due to differences in the treatment of the thermal energy during
the unbinding procedure. We acknowledge that the handling of gas in halo
finders is something that needs to be dealt with carefully, and the precise
treatment may depend sensitively upon the scientific problem being studied.Comment: 14 interesting pages, 17 beautiful figures, and 2 informative tables
accepted for publication in MNRAS (matches published version
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