A genetic basis for atopic dermatitis (AD) has long been recognized. Historic documents allude to family history of disease as a risk factor. Before characterization of the human genome, heritability ...studies combined with family-based linkage studies supported the definition of AD as a complex trait in that interactions between genes and environmental factors and the interplay between multiple genes contribute to disease manifestation. A summary of more than 100 published reports on genetic association studies through mid-2009 implicates 81 genes, in 46 of which at least 1 positive association with AD has been demonstrated. Of these, the gene encoding filaggrin (FLG) has been most consistently replicated. Most candidate gene studies to date have focused on adaptive and innate immune response genes, but there is increasing interest in skin barrier dysfunction genes. This review examines the methods that have been used to identify susceptibility genes for AD and how the underlying pathology of this disease has been used to select candidate genes. Current challenges and the potential effect of new technologies are discussed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is a large body of evidence revealing that minorities-in particular, Black citizens-are overrepresented in the criminal justice system. But the causes of these inequalities have been difficult ...to pin down. One line of work suggests the inequalities in arrest may be traced to inequalities in exposure to school discipline. Specifically, the school-to-prison pipeline literature suggests inequalities in school disciplinary practices may go on to produce inequalities in arrest prevalence. In this article, we draw on a large nationally representative sample to test the hypothesis that racial inequalities in school-based punishments will (partially) explain inequalities in adulthood arrest. We find support for this pathway and, by drawing on recent developments in epidemiology, produce initial estimates of the degree to which policymakers might be able to close the racial gap in arrest if it were possible to close the racial gap in school discipline.
Full text
Available for:
CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
In this review we discuss conventional methods of performing biological assays and molecular identification and highlight their advantages and limitations. An alternative approach based on magnetic ...nanotechnology is then presented. Firstly, magnetic carriers are introduced and their biocompatibility and functionalisation discussed, with spotlights on functionalisation via self assembled monolayers and on methods of reducing nonspecific binding. In addition an introduction is provided to the basic physical concepts behind the various types of sensors used to detect magnetic labels. Finally, progress in the field of magnetic biosensors and the outlook for the future are discussed.
Full text
Available for:
CEKLJ, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Single-electron circuits of the future, consisting of a network of quantum dots, will require a mechanism to transport electrons from one functional part of the circuit to another. For example, in a ...quantum computer decoherence and circuit complexity can be reduced by separating quantum bit (qubit) manipulation from measurement and by providing a means of transporting electrons between the corresponding parts of the circuit. Highly controlled tunnelling between neighbouring dots has been demonstrated, and our ability to manipulate electrons in single- and double-dot systems is improving rapidly. For distances greater than a few hundred nanometres, neither free propagation nor tunnelling is viable while maintaining confinement of single electrons. Here we show how a single electron may be captured in a surface acoustic wave minimum and transferred from one quantum dot to a second, unoccupied, dot along a long, empty channel. The transfer direction may be reversed and the same electron moved back and forth more than sixty times-a cumulative distance of 0.25 mm-without error. Such on-chip transfer extends communication between quantum dots to a range that may allow the integration of discrete quantum information processing components and devices.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Injection of spin currents into solids is crucial for exploring spin physics and spintronics. There has been significant progress in recent years in spin injection into high-resistivity materials, ...for example, semiconductors and organic materials, which uses tunnel barriers to circumvent the impedance mismatch problem; the impedance mismatch between ferromagnetic metals and high-resistivity materials drastically limits the spin-injection efficiency. However, because of this problem, there is no route for spin injection into these materials through low-resistivity interfaces, that is, Ohmic contacts, even though this promises an easy and versatile pathway for spin injection without the need for growing high-quality tunnel barriers. Here we show experimental evidence that spin pumping enables spin injection free from this condition; room-temperature spin injection into GaAs from Ni(81)Fe(19) through an Ohmic contact is demonstrated through dynamical spin exchange. Furthermore, we demonstrate that this exchange can be controlled electrically by applying a bias voltage across a Ni(81)Fe(19)/GaAs interface, enabling electric tuning of the spin-pumping efficiency.
Full text
Available for:
IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Large changes in the magnetization of ferromagnetic films can be electrically driven by non-180° ferroelectric domain switching in underlying substrates, but the shear components of the strains that ...mediate these magnetoelectric effects have not been considered so far. Here we reveal the presence of these shear strains in a polycrystalline film of Ni on a 0.68Pb(Mg
Nb
)O
-0.32PbTiO
substrate in the pseudo-cubic (011)
orientation. Although vibrating sample magnetometry records giant magnetoelectric effects that are consistent with the hitherto expected 90° rotations of a global magnetic easy axis, high-resolution vector maps of magnetization (constructed from photoemission electron microscopy data, with contrast from X-ray magnetic circular dichroism) reveal that the local magnetization typically rotates through smaller angles of 62-84°. This shortfall with respect to 90° is a consequence of the shear strain associated with ferroelectric domain switching. The non-orthogonality represents both a challenge and an opportunity for the development and miniaturization of magnetoelectric devices.
This paper discusses a novel fully implicit formulation for a one-dimensional electrostatic particle-in-cell (PIC) plasma simulation approach. Unlike earlier implicit electrostatic PIC approaches ...(which are based on a linearized Vlasov–Poisson formulation), ours is based on a nonlinearly converged Vlasov–Ampére (VA) model. By iterating particles and fields to a tight nonlinear convergence tolerance, the approach features superior stability and accuracy properties, avoiding most of the accuracy pitfalls in earlier implicit PIC implementations. In particular, the formulation is stable against temporal (Courant–Friedrichs–Lewy) and spatial (aliasing) instabilities. It is charge- and energy-conserving to numerical round-off for arbitrary implicit time steps (unlike the earlier “energy-conserving” explicit PIC formulation, which only conserves energy in the limit of arbitrarily small time steps). While momentum is not exactly conserved, errors are kept small by an adaptive particle sub-stepping orbit integrator, which is instrumental to prevent particle tunneling (a deleterious effect for long-term accuracy). The VA model is orbit-averaged along particle orbits to enforce an energy conservation theorem with particle sub-stepping. As a result, very large time steps, constrained only by the dynamical time scale of interest, are possible without accuracy loss. Algorithmically, the approach features a Jacobian-free Newton–Krylov solver. A main development in this study is the nonlinear elimination of the new-time particle variables (positions and velocities). Such nonlinear elimination, which we term particle enslavement, results in a nonlinear formulation with memory requirements comparable to those of a fluid computation, and affords us substantial freedom in regards to the particle orbit integrator. Numerical examples are presented that demonstrate the advertised properties of the scheme. In particular, long-time ion acoustic wave simulations show that numerical accuracy does not degrade even with very large implicit time steps, and that significant CPU gains are possible.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The structure of graphite oxide (GO) has been systematically studied using various tools such as SEM, TEM, XRD, Fourier transform infrared spectroscopy (FT-IR), X-ray photoemission spectroscopy ...(XPS), 13C solid-state NMR, and O K-edge X-ray absorption near edge structure (XANES). The TEM data reveal that GO consists of amorphous and crystalline phases. The XPS data show that some carbon atoms have sp3 orbitals and others have sp2 orbitals. The ratio of sp2 to sp3 bonded carbon atoms decreases as sample preparation times increase. The 13C solid-state NMR spectra of GO indicate the existence of OH and O groups for which peaks appear at 60 and 70 ppm, respectively. FT-IR results corroborate these findings. The existence of ketone groups is also implied by FT-IR, which is verified by O K-edge XANES and 13C solid-state NMR. We propose a new model for GO based on the results; O, OH, and CO groups are on the surface.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Covering: 1980 to end 2014
A diverse range of strategies leading to natural product derived or inspired screening libraries aims to increase the number of new chemical entities emerging per year. ...However, the use of isolated natural products as scaffolds for the semi-synthesis of larger biological screening libraries remains rare. This particular method avoids the time-consuming and resource intensive
de novo
synthetic strategy for scaffold production, and has become more feasible through improvements to synthetic and isolation methodologies. This Highlight examines the increasing popularity of small- to large-sized screening libraries generated directly from isolated natural products. Several of the examples detailed herein show how this strategy can lead to improvements in not only potency but also other important (and often forgotten) drug discovery parameters such as toxicity, selectivity, lipophilicity and bioavailability. However, there are still improvements to be made to this method, particularly in the choice of the natural product scaffold and the derivatising reagents used. Avoidance of known nuisance compounds or structural alert motifs (
e.g.
PAINS) that interfere with bioactivity screens, and impact downstream drug development will play a significant role in the future success of this methodology. Incorporation of rational design strategies that take into account the physicochemical parameters (
e.g.
log
P
, MW, HBA, HBD) of the final semi-synthetic library analogues will also facilitate the discovery and development of leads and drugs. A multi-pronged approach to drug discovery that incorporates the use of isolated natural product scaffolds for library generation will surely be beneficial.
This Highlight examines the use of isolated natural products as scaffolds in the semi-synthesis of drug discovery libraries, and the potential of this rarely used method to contribute to successful natural product library generation strategies.
This study examined the evolution of physical and technical soccer performance across a 7-season period in the English Premier League. Match performance observations (n=14 700) were analysed for ...emergent trends. Total distance covered during a match was ~2% lower in 2006-07 compared to 2012-13. Across 7 seasons, high-intensity running distance and actions increased by ~30% (890±299 vs. 1 151±337 m, p<0.001; ES: 0.82) and ~50% (118±36 vs. 176±46, p<0.001; ES: 1.41), respectively. Sprint distance and number of sprints increased by ~35% (232±114 vs. 350±139 m, p<0.001; ES: 0.93) and ~85% (31±14 vs. 57±20, p<0.001; ES: 1.46), respectively. Mean sprint distance was shorter in 2012-13 compared to 2006-07 (5.9±0.8 vs. 6.9±1.3 m, p<0.001; ES: 0.91), with the proportion of explosive sprints increasing (34±11 vs. 47±9%, p<0.001; ES: 1.31). Players performed more passes (35±17 vs. 25±13, p<0.001; ES: 0.66) and successful passes (83±10% vs. 76±13%, p<0.001; ES: 0.60) in 2012-13 compared to 2006-07. Whereas the number of short and medium passes increased across time (p<0.001; ES>0.6), the number of long passes varied little (p<0.001; ES: 0.11). This data demonstrates evolution of physical and technical parameters in the English Premier League, and could be used to aid talent identification, training and conditioning preparation.
PDF
