A functional characterisation of the PCSK6 locus associated with handedness

Humans display a 90% population level bias towards right-handedness, implying the vast majority of people have a left-hemisphere dominant for motor control. Although handedness presents a weak, but very consistent heritability across the literature (estimated to be approximately 25%), to date few genetic loci associated with this complex trait have been identified and replicated in subsequent studies. One such gene which has been found to be associated with handedness and subsequently replicated is PCSK6, most recently through a quantitative GWAS (P < 0.5*10⁻⁸, Brandler et al. (2013)). Interestingly, PCSK6 is known to activate Nodal, a morphogen involved in a highly conserved bilaterian pathway known to regulate left-right body axis determination. Here I present the first molecular characterisation of a handedness-associated region by conducting a detailed functional analysis of the PCSK6 locus, combining genetic analysis, in silico prediction and molecular assays to investigate how common genetic variants influence handedness-related phenotypes. Specifically, I defined the associated locus to be 12.7 kb in size, spanning a predicted 1.8 kb bidirectional promoter which controls the expression of both an antisense long non-coding RNA (lncRNA), and a novel short PCSK6 isoform. A series of luciferase-expressing constructs were generated to characterise the promoter, identifying a minimal sequence capable of driving transcription in a sense strand direction. I have demonstrated experimentally that one of the top associated markers in previous GWA studies, rs11855145, directly creates/disrupts a suspected transcription factor bind site in the vicinity of this bidirectional promoter. Further functional studies of the genetic variation within PCSK6 may help explain the molecular regulatory mechanisms affecting gene expression. This project provides a model for assays to study other GWAS-nominated candidate genes, and in particular for establishing the role of noncoding variants. The findings from this study support the role of common variants in influencing complex phenotypes, such as handedness

A high-resolution model of the external and induced magnetic field at the Earth’s surface in the northern hemisphere

We describe a method of producing high-resolution models of the Earth’s combined external and induced magnetic field (EIMF) using the method of Empirical Orthogonal Functions (EOFs) applied to the SuperMAG archive of ground-based magnetometer data. EOFs partition the variance of a system into independent modes, allowing us to extract the spatiotemporal patterns of greatest dynamical importance without applying the a priori assumptions of other methods (such as spherical harmonic analysis, parameterised averaging, or multi-variate regression). We develop an approach based on that of Beckers and Rixen [2003] and use the EOF modes to infill missing data in a self-consistent manner. Applying our method to a north polar case study spanning February 2001 (chosen for its proximity to solar maximum and good data coverage), we demonstrate that 41.7% and 9.4% of variance is explained by the leading two modes, respectively describing the temporal variations of the Disturbance Polar types 2 and 1 (DP2 and DP1) patterns. A further 14.1% of variance is explained by four modes that describe separate aspects of the motion of the DP1 and DP2 systems. Thus, collectively over 65% of variance is described by the leading 6 modes and is attributable to DP1 and DP2. This attribution is based on inspection of the spatial morphology of the modes, and analysis of the temporal variation of the mode amplitudes with respect to solar wind measures and substorm occurrence. This study is primarily a demonstration of the technique and a prelude to a model spanning the full solar cycle

La homosexualidad y la Biblia: Practicando textos seguros

This article addresses the interpretations of Biblical texts used against queer believers. Commonly known as «texts of terror,» they have been cited as God-given prohibitions of same-sex relationships. The analysis uncovers the bias and the various representations of gender and sexuality in the Ancient Near East and the Greco-Roman contexts. Drawing from extensive scholarly work featuring contemporary hermeneutics the article challenges the thesis that same-sex relationships are the point of prohibitions. It concludes that the background of Ancient Near East and Greco-Roman worldview do not allow for anachronistic extrapolations of contemporary notions of gender and sexuality into the heart of the sacred scriptures

Improved description of Earth’s external magnetic fields and their source regions using satellite data

In near-Earth space, highly spatio-temporally variant magnetic fields result from solar-terrestrial magnetic interaction. These near-Earth external fields currently represent the largest source of error in efforts to model the magnetic field produced in the Earth’s interior. Starting in 1999, the Decade of Geopotential Field Research (Friis-Christensen et al., 2009) has greatly increased the amount of available low-Earth orbit (LEO) satellite magnetic data. These data have driven many advances in field modelling, yet have highlighted that LEO measurements are particularly susceptible to contamination from external fields. This thesis presents a series of studies attempting to describe the external fields in more detail, in order that they can be more effectively separated from the internal fields in magnetic modelling efforts. A range of analysis methods, different for each study, are applied to satellite and ground-based observatory data. Mandea and Olsen’s (2006) method of estimating the secular variation (SV) of the internal field from satellite data via ‘Virtual Observatories’ (VOs) is applied to synthetic data from the upcoming Swarm constellation satellite mission of the European Space Agency. Beggan (2009) found VOs constructed from CHAMP satellite data to be contaminated with external field signals which appeared to have a significant local time (LT) dependence. I find that utilising the increased coverage of LT sectors offered by the Swarm constellation geometry does not significantly decrease the contamination. Following this surprising result I tested a wide range of methods aimed at reducing the VO contamination from each parameterised external field source region. In anticipation of future studies using real data, I used the results of the tests to provide a more complete description of the external field variations affecting analyses of geographically-fixed magnetic phenomena when using satellite data and spherical harmonic analysis (SHA). Ionospheric electric currents flowing at LEO altitudes are known to violate the assumption of measurements taken in a source-free space, required in SHA-based models of the magnetic field. In order to better describe the electromagnetic environment at LEO altitudes, I use data from the Ørsted and CHAMP satellites to calculate the current density from Amp`ere’s integral. Vector magnetic data from discrete overflights of the two satellites (at different altitudes) are rotated into the along-track frame to define the integral loop and its ‘surface area’, permitting estimation of the predominantly zonal current density flowing in the region between the two orbital paths. I designed selection criteria to extract geometrically-stable overflights spanning the range of LTs twice in the 6 years of mutually available satellite vector data. From these overflights I resolve current densities in the range 0:1 μA=m2, with the distribution of current largely matching the LT progression of the Appleton anomaly. I applied detailed tests to check for biases intrinsic to the method, and present results free of systematic errors. The results are compared with the predictions of the CTIP (Coupled Thermosphere-Ionosphere-Plasmasphere) model of ionospheric composition and temperature, showing a typically good spatiotemporal agreement. I find persistent current intensifications between geomagnetic latitudes of 30 and 50 in the post-midnight, pre-dawn sector, a region which has been previously considered to be relatively free of currents. External fields induce currents in the Earth’s conducting mantle, the magnetic fields of which add to the field measured at and above the Earth’s surface. The morphology of the long-period inducing field is poorly resolved on timescales of months to years, reducing the accuracy of mantle induction studies (a key part of the Swarm mission). I improve the description of its morphology via the method of Empirical Orthogonal Functions (EOFs), which I apply to over a decade of ground-based observatory data. EOFs provide a decomposition of the spatiotemporal structures contained in the magnetic field data, with partitions arising from the data themselves, overcoming the relatively simplistic assumptions made about the inducing field morphology in LT. The results of vector data EOF analyses are presented, but I rely primarily on scalar analyses which are more fitting for this study. I overcome the limitations of the irregular observatory distribution with a novel spatial weighting matrix, combining the output from multiple EOF analyses to greatly improve the data coverage in LT. I find that the seasonal variation of the inducing field is more important than the variation of the symmetric ring current on annual periods, and that dawn-dusk asymmetry should be accounted for to increase the accuracy of mantle conductivity estimates based on data covering the decadal timescales of the solar cycle

Fibrodysplasia Ossificans Progressiva: Clinical and Genetic Aspects

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites. The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP. Children who have FOP appear normal at birth except for congenital malformations of the great toes. During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups) occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. These flare-ups transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone, rendering movement impossible. Patients with atypical forms of FOP have been described. They either present with the classic features of FOP plus one or more atypical features [FOP plus], or present with major variations in one or both of the two classic defining features of FOP [FOP variants]. Classic FOP is caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor. Atypical FOP patients also have heterozygous ACVR1 missense mutations in conserved amino acids. The diagnosis of FOP is made by clinical evaluation. Confirmatory genetic testing is available. Differential diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema, soft tissue sarcoma, desmoid tumors, aggressive juvenile fibromatosis, and non-hereditary (acquired) heterotopic ossification. Although most cases of FOP are sporadic (noninherited mutations), a small number of inherited FOP cases show germline transmission in an autosomal dominant pattern. At present, there is no definitive treatment, but a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue edema seen in the early stages of the disease. Preventative management is based on prophylactic measures against falls, respiratory decline, and viral infections. The median lifespan is approximately 40 years of age. Most patients are wheelchair-bound by the end of the second decade of life and commonly die of complications of thoracic insufficiency syndrome

Queering Jesus: LGBTQI Dangerous Remembering and Imaginative Resistance

Queering Jesus is a call to remember the danger of the story of Jesus. The primary aim of this article is to offer a comprehensive survey of the representation of queer Jesus. Building upon the deconstructive work of Johannes Baptist Metz and the notion of the dangerous memories of Jesus’s suffering and death (memoria passsionis), this article tries to make sense of the deconstruction of heteronormative and cisgender constructions of a white, male Jesus that supports the exclusion and oppression of queer folks. Queer constructions of Jesus in biblical interpretation and popular media are accused of being blasphemous fictions, while the same charge can be levied against the constructions of heteronormative and cisgender Christian churches who marginalize and stigmatize LGBTQI people. The imaginative remembering of the dangerous story of Jesus empowers queer folks to liberate and create a queer Jesus who allows LGBTQI Christians to experience the liberating presence of Jesus, to experience themselves as beloved, and to empower them to take back an inclusive Christianity

Dipole Moment of Ammonia‐Borane

The dipole moment of ammonia‐borane, H3NBH3, has been measured as 4.9 debye units in dioxane solution; the results are discussed briefly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71099/2/JCPSA6-29-1-1-1.pd

Spin Readout and Initialization in a Semiconductor Quantum Dot

Electron spin qubits in semiconductors are attractive from the viewpoint of long coherence times. However, single spin measurement is challenging. Several promising schemes incorporate ancillary tunnel couplings that may provide unwanted channels for decoherence. Here, we propose a novel spin-charge transduction scheme, converting spin information to orbital information within a single quantum dot by microwave excitation. The same quantum dot can be used for rapid initialization, gating, and readout. We present detailed modeling of such a device in silicon to confirm its feasibility.Comment: Published versio

The Neon Abundance in the Ejecta of QU Vul From Late-Epoch IR Spectra

We present ground-based SpectroCam-10 mid-infrared, MMT optical, and Spitzer Space Telescope IRS mid-infrared spectra taken 7.62, 18.75, and 19.38 years respectively after the outburst of the old classical nova QU Vulpeculae (Nova Vul 1984 #2). The spectra of the ejecta are dominated by forbidden line emission from neon and oxygen. Our analysis shows that neon was, at the first and last epochs respectively, more than 76 and 168 times overabundant by number with respect to hydrogen compared to the solar value. These high lower limits to the neon abundance confirm that QU Vul involved a thermonuclear runaway on an ONeMg white dwarf and approach the yields predicted by models of the nucleosynthesis in such events.Comment: ApJ 2007 accepted, 18 pages, including 5 figures, 1 tabl