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The Effects of Neurosteroids, such as Pregnenolone Sulfate and its receptor, TrpM3 in the Retina.
Pregnenolone sulfate (PregS) is the precursor to all steroid hormones and is produced in neurons in an activity dependent manner. Studies have shown that PregS production is upregulated during certain critical periods of development, such as in the first year of life in humans, during adolescence, and during pregnancy. Conversely, PregS is decreased during aging, as well as in several neurodevelopmental and neurodegenerative conditions. There are several known targets of PregS, such as a positive allosteric modulator NMDA receptors, sigma1 receptor, and as a negative allosteric modulator of GABA-A receptors. Recently a transient receptor potential channel, TrpM3 has been shown to be activated by PregS. TrpM3 is a heat sensitive (between 33-40oC), non-selective cation channel that is outwardly rectifying. PregS has been shown to increase the frequency of post-synaptic currents in the hippocampus and developing cerebellum, induce calcium transients in a subset of retinal ganglion cells, and enhance memory formation in rodents. Furthermore, PregS mediated TrpM3 activation induces calcium dependent transcription of early immediate genes, suggesting that activation of this channel may produce lasting effects on cells and systems in which it is activated. Because PregS is abundant during critical periods of development, we hypothesized that it may play a significant role during development. Furthermore, the role of PregS or its receptor TrpM3, has not previously been well characterized in the retina. To address this question, in this dissertation, we examine the role of the neurosteroid PregS and its receptor, TrpM3, on retinal waves, which are characteristic of specific stages of synaptic development and connectivity. Briefly, we show that PregS induces a TrpM3 dependent prolonged calcium transient, which is absent in the TrpM3-/- animals and increases the correlation of cell participation in waves. We also show that TrpM3 increases the frequency of post-synaptic currents, indicating a mechanism of action presynaptic to retinal ganglion cells, but that TrpM3 is expressed primarily in RGCs and Müller glia. Taken together, our results indicate that both PregS and TrpM3 are important in modulating spontaneous synaptic activity during development
Entropy and the Economy of Violence: Anthropophagy and Sacrificial Violence in Late Modernity
In this project, I explore the relationship of biosocial perspectives, specifically the study of energy and entropy, to contemporary work in criminology and social theory. After working through an elaboration of entropy, I explore its relevance to social life through an eclectic but necessary survey of a key set of scholars whose work focuses upon the sacrifice and criminalization of the poor, the intensification of exclusion and genocidal contexts, and finally, the possibility of a politics of change through indigenous knowledges. Bringing these various schools of thought together allows us to see the interdisciplinary linkages that might better reveal the urgency of emergency in our contemporary era
Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy
Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigenspecific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics
The Murchison Widefield Array: Design Overview
The Murchison Widefield Array (MWA) is a dipole-based aperture array
synthesis telescope designed to operate in the 80-300 MHz frequency range. It
is capable of a wide range of science investigations, but is initially focused
on three key science projects. These are detection and characterization of
3-dimensional brightness temperature fluctuations in the 21cm line of neutral
hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10,
solar imaging and remote sensing of the inner heliosphere via propagation
effects on signals from distant background sources,and high-sensitivity
exploration of the variable radio sky. The array design features 8192
dual-polarization broad-band active dipoles, arranged into 512 tiles comprising
16 dipoles each. The tiles are quasi-randomly distributed over an aperture
1.5km in diameter, with a small number of outliers extending to 3km. All
tile-tile baselines are correlated in custom FPGA-based hardware, yielding a
Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point
spread function (PSF) quality. The correlated data are calibrated in real time
using novel position-dependent self-calibration algorithms. The array is
located in the Murchison region of outback Western Australia. This region is
characterized by extremely low population density and a superbly radio-quiet
environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings
of the IEE
A new layout optimization technique for interferometric arrays, applied to the MWA
Antenna layout is an important design consideration for radio interferometers
because it determines the quality of the snapshot point spread function (PSF,
or array beam). This is particularly true for experiments targeting the 21 cm
Epoch of Reionization signal as the quality of the foreground subtraction
depends directly on the spatial dynamic range and thus the smoothness of the
baseline distribution. Nearly all sites have constraints on where antennas can
be placed---even at the remote Australian location of the MWA (Murchison
Widefield Array) there are rock outcrops, flood zones, heritages areas,
emergency runways and trees. These exclusion areas can introduce spatial
structure into the baseline distribution that enhance the PSF sidelobes and
reduce the angular dynamic range. In this paper we present a new method of
constrained antenna placement that reduces the spatial structure in the
baseline distribution. This method not only outperforms random placement
algorithms that avoid exclusion zones, but surprisingly outperforms random
placement algorithms without constraints to provide what we believe are the
smoothest constrained baseline distributions developed to date. We use our new
algorithm to determine antenna placements for the originally planned MWA, and
present the antenna locations, baseline distribution, and snapshot PSF for this
array choice.Comment: 12 pages, 6 figures, 1 table. Accepted for publication in MNRA
WSClean : an implementation of a fast, generic wide-field imager for radio astronomy
This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2014 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.Astronomical widefield imaging of interferometric radio data is computationally expensive, especially for the large data volumes created by modern non-coplanar many-element arrays. We present a new widefield interferometric imager that uses the w-stacking algorithm and can make use of the w-snapshot algorithm. The performance dependencies of CASA's w-projection and our new imager are analysed and analytical functions are derived that describe the required computing cost for both imagers. On data from the Murchison Widefield Array, we find our new method to be an order of magnitude faster than w-projection, as well as being capable of full-sky imaging at full resolution and with correct polarisation correction. We predict the computing costs for several other arrays and estimate that our imager is a factor of 2-12 faster, depending on the array configuration. We estimate the computing cost for imaging the low-frequency Square-Kilometre Array observations to be 60 PetaFLOPS with current techniques. We find that combining w-stacking with the w-snapshot algorithm does not significantly improve computing requirements over pure w-stacking. The source code of our new imager is publicly released.Peer reviewedFinal Published versio
Interferometric imaging with the 32 element Murchison Wide-field Array
The Murchison Wide-field Array (MWA) is a low frequency radio telescope,
currently under construction, intended to search for the spectral signature of
the epoch of re-ionisation (EOR) and to probe the structure of the solar
corona. Sited in Western Australia, the full MWA will comprise 8192 dipoles
grouped into 512 tiles, and be capable of imaging the sky south of 40 degree
declination, from 80 MHz to 300 MHz with an instantaneous field of view that is
tens of degrees wide and a resolution of a few arcminutes. A 32-station
prototype of the MWA has been recently commissioned and a set of observations
taken that exercise the whole acquisition and processing pipeline. We present
Stokes I, Q, and U images from two ~4 hour integrations of a field 20 degrees
wide centered on Pictoris A. These images demonstrate the capacity and
stability of a real-time calibration and imaging technique employing the
weighted addition of warped snapshots to counter extreme wide field imaging
distortions.Comment: Accepted for publication in PASP. This is the draft before journal
typesetting corrections and proofs so does contain formatting and journal
style errors, also has with lower quality figures for space requirement
The Murchison Widefield Array
It is shown that the excellent Murchison Radio-astronomy Observatory site
allows the Murchison Widefield Array to employ a simple RFI blanking scheme and
still calibrate visibilities and form images in the FM radio band. The
techniques described are running autonomously in our calibration and imaging
software, which is currently being used to process an FM-band survey of the
entire southern sky.Comment: Accepted for publication in Proceedings of Science [PoS(RFI2010)016].
6 pages and 3 figures. Presented at RFI2010, the Third Workshop on RFI
Mitigation in Radio Astronomy, 29-31 March 2010, Groningen, The Netherland
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