Exploring noncoding variation in human diseases and disorders through targeted sequencing and functional prediction

The identification of non-coding single nucleotide polymorphisms (SNPs) and short insertions or deletions (indels) that are causative or contributory to human diseases and disorders is limited by the functional knowledge of the non-coding genome. This work demonstrates multiple approaches to elucidate functional variation in the non-coding genome by using homogenous populations or pedigrees of individuals with shared diseases and disorders, including Obesity, Schizophrenia, Anosmia and Mitochondrial Depletion Syndrome. A vast bank of non-coding variation has been created and can be utilised for population analysis. Using supporting evidence of developmental contributions to the disorders studied and genome interaction data, high coverage sequencing of targeted regions and subsequent bioinformatics analysis suggests multiple new disease-associated non-coding variants. Combining available variant function predictor tools and publicly available functional data, a selection of variants are prioritised as potentially causative or contributory and their affect on the region’s function in development as an enhancer is assessed in Zebrafish. In addition, deep-sequencing and bioinformatics analysis in mouse models of MPV17 deletion contributes to the understanding of mitochondrial depletion syndrome

Precious metals as safe haven assets in the South African market

Abstract: The role of precious metals as hedges and safe havens has been extensively studied across various markets. However, no precious metals other than gold have been considered in a South African setting. This study extends previous literature by making use of the methodology established by Baur and Lucey (2010) to determine which of the four precious metals provides the most viable hedge and safe haven in relation to the domestic stock and bond markets for South African investors? The results suggest that all four precious metals have significant hedging properties in relation to domestic bond market but not the stock market. It was also determined that while all four metals contain safe haven properties, gold is the only precious metal to act as a significant safe haven against both South African stocks and bonds

Positive solutions of Schr\"odinger equations and fine regularity of boundary points

Given a Lipschitz domain $\Omega$ in ${\mathbb R} ^N$ and a nonnegative potential $V$ in $\Omega$ such that $V(x)\, d(x,\partial \Omega)^2$ is bounded in $\Omega$ we study the fine regularity of boundary points with respect to the Schr\"odinger operator $L_V:= \Delta -V$ in $\Omega$. Using potential theoretic methods, several conditions equivalent to the fine regularity of $z \in \partial \Omega$ are established. The main result is a simple (explicit if $\Omega$ is smooth) necessary and sufficient condition involving the size of $V$ for $z$ to be finely regular. An essential intermediate result consists in a majorization of $\int_A | {\frac {u} {d(.,\partial \Omega)}} | ^2\, dx$ for $u$ positive harmonic in $\Omega$ and $A \subset \Omega$. Conditions for almost everywhere regularity in a subset $A$ of $\partial \Omega$ are also given as well as an extension of the main results to a notion of fine ${\mathcal L}_1 | {\mathcal L}_0$-regularity, if ${\mathcal L}_j={\mathcal L}-V_j$, $V_0,\, V_1$ being two potentials, with $V_0 \leq V_1$ and ${\mathcal L}$ a second order elliptic operator.Comment: version 1. 23 pages version 3. 28 pages. Mainly a typo in Theorem 1.1 is correcte

New light on gamma-ray burst host galaxies with Herschel

Until recently, dust emission has been detected in very few host galaxies of gamma-ray bursts (GRBHs). With Herschel, we have now observed 17 GRBHs up to redshift z~3 and detected seven of them at infrared (IR) wavelengths. This relatively high detection rate (41%) may be due to the composition of our sample which at a median redshift of 1.1 is dominated by the hosts of dark GRBs. Although the numbers are small, statistics suggest that dark GRBs are more likely to be detected in the IR than their optically-bright counterparts. Combining our IR data with optical, near-infrared, and radio data from our own datasets and from the literature, we have constructed spectral energy distributions (SEDs) which span up to 6 orders of magnitude in wavelength. By fitting the SEDs, we have obtained stellar masses, dust masses, star-formation rate (SFR), and extinctions for our sample galaxies. We find that GRBHs are galaxies that tend to have a high specfic SFR (sSFR), and like other star-forming galaxies, their ratios of dust-to-stellar mass are well correlated with sSFR. We incorporate our Herschel sample into a larger compilation of GRBHs, and compare this combined sample to SFR-weighted median stellar masses of the widest, deepest galaxy survey to date. This is done in order to establish whether or not GRBs can be used as an unbiased tracer of cosmic comoving SFR density (SFRD) in the universe. In contrast with previous results, this comparison shows that GRBHs are medium-sized galaxies with relatively high sSFRs; stellar masses and sSFRs of GRBHs as a function of redshift are similar to what is expected for star-forming galaxy populations at similar redshifts. We conclude that there is no strong evidence that GRBs are biased tracers of SFRD; thus they should be able to reliably probe the SFRD to early epochs.Comment: 18 pages, 9 figures, accepted for publication in A&A. Revised to include Fig. 6, mistakenly omitted in origina

Towards a Formally Verified Security Monitor for VM-based Confidential Computing

Confidential computing is a key technology for isolating high-assurance applications from the large amounts of untrusted code typical in modern systems. Existing confidential computing systems cannot be certified for use in critical applications, like systems controlling critical infrastructure, hardware security modules, or aircraft, as they lack formal verification. This paper presents an approach to formally modeling and proving a security monitor. It introduces a canonical architecture for virtual machine (VM)-based confidential computing systems. It abstracts processor-specific components and identifies a minimal set of hardware primitives required by a trusted security monitor to enforce security guarantees. We demonstrate our methodology and proposed approach with an example from our Rust implementation of the security monitor for RISC-V

Optical Images and Source Catalog of AKARI North Ecliptic Pole Wide Survey Field

We present the source catalog and the properties of the $B-, R-$, and $I-$band images obtained to support the {\it AKARI} North Ecliptic Pole Wide (NEP-Wide) survey. The NEP-Wide is an {\it AKARI} infrared imaging survey of the north ecliptic pole covering a 5.8 deg$^2$ area over 2.5 -- 6 \micron wavelengths. The optical imaging data were obtained at the Maidanak Observatory in Uzbekistan using the Seoul National University 4k $\times$ 4k Camera on the 1.5m telescope. These images cover 4.9 deg$^2$ where no deep optical imaging data are available. Our $B-, R-$, and $I-$band data reach the depths of $\sim$23.4, $\sim$23.1, and $\sim$22.3 mag (AB) at 5$\sigma$, respectively. The source catalog contains 96,460 objects in the $R-$band, and the astrometric accuracy is about 0.15\arcsec at 1$\sigma$ in each RA and Dec direction. These photometric data will be useful for many studies including identification of optical counterparts of the infrared sources detected by {\it AKARI}, analysis of their spectral energy distributions from optical through infrared, and the selection of interesting objects to understand the obscured galaxy evolution.Comment: 39 pages, 12 figure

Turbulent ‘stopping plumes’ and plume pinch-off in uniform surroundings

Observations of turbulent convection in the environment are of variously sus- tained plume-like flows or intermittent thermal-like flows. At different times of the day the prevailing conditions may change and consequently the observed flow regimes may change. Understanding the link between these flows is of practical importance meteorologically, and here we focus our interest upon plume-like regimes that break up to form thermal-like regimes. It has been shown that when a plume rises from a boundary with low conductivity, such as arable land, the inability to maintain a rapid enough supply of buoyancy to the plume source can result in the turbulent base of the plume separating and rising away from the source. This plume ‘pinch-off’ marks the onset of the intermittent thermal-like behavior. The dynamics of turbulent plumes in a uniform environment are explored in order to investigate the phenomenon of plume pinch-off. The special case of a turbulent plume having its source completely removed, a ‘stopping plume’, is considered in particular. The effects of forcing a plume to pinch-off, by rapidly reducing the source buoyancy flux to zero, are shown experi- mentally. We release saline solution into a tank filled with fresh water generating downward propagating steady turbulent plumes. By rapidly closing the plume nozzle, the plumes are forced to pinch-off. The plumes are then observed to detach from the source and descend into the ambient. The unsteady buoyant region produced after pinch-off, cannot be described by the power-law behavior of either classical plumes or thermals, and so the terminology ‘stopping plume’ (analogous to a ‘starting plume’) is adopted for this type of flow. The propagation of the stopping plume is shown to be approximately linearly dependent on time, and we speculate therefore that the closure of the nozzle introduces some vorticity into the ambient, that may roll up to form a vortex ring dominating the dynamics of the base of a stopping plume

The Spitzer View of Low-Metallicity Star Formation: III. Fine Structure Lines, Aromatic Features, and Molecules

We present low- and high-resolution Spitzer/IRS spectra, supplemented by IRAC and MIPS measurements, of 22 blue compact dwarf (BCD) galaxies. The BCD sample spans a wide range in oxygen abundance [12+Log(O/H) between 7.4 and 8.3], and hardness of the interstellar radiation field (ISRF). The IRS spectra provide us with a rich set of diagnostics to probe the physics of star and dust formation in very low-metallicity environments. We find that metal-poor BCDs have harder ionizing radiation than metal-rich galaxies: [OIV] emission is roughly 4 times as common as [FeII] emission. They also have a more intense ISRF, as indicated by the 71 to 160micron luminosity ratio. Two-thirds of the sample (15 BCDs) show PAH features, although the fraction of PAH emission normalized to the total infrared (IR) luminosity is considerably smaller in metal-poor BCDs (~0.5%) than in metal-rich star-forming galaxies (~10%). We find several lines of evidence for a deficit of small PAH carriers at low metallicity, and attribute this to destruction by a hard, intense ISRF, only indirectly linked to metal abundance. Our IRS spectra reveal a variety of H2 rotational lines, and more than a third of the objects in our sample (8 BCDs) have >=3sigma detections in one or more of the four lowest-order transitions. The warm gas masses in the BCDs range from 10^3 to 10^8 Msun, and can be comparable to the neutral hydrogen gas mass; relative to their total IR luminosities, some BCDs contain more H2 than SINGS galaxies.Comment: Accepted by ApJ: 70 pages in draft form, 6 tables, 22 figure

Conformations of Linear DNA

We examine the conformations of a model for under- and overwound DNA. The molecule is represented as a cylindrically symmetric elastic string subjected to a stretching force and to constraints corresponding to a specification of the link number. We derive a fundamental relation between the Euler angles that describe the curve and the topological linking number. Analytical expressions for the spatial configurations of the molecule in the infinite- length limit were obtained. A unique configuraion minimizes the energy for a given set of physical conditions. An elastic model incorporating thermal fluctuations provides excellent agreement with experimental results on the plectonemic transition.Comment: 5 pages, RevTeX; 6 postscript figure