Comment on "Are periodic solar wind number density structures formed in the solar corona?" by N. M. Viall et al., 2009, Geophys. Res. Lett., 36, L23102, doi:10.1029/2009GL041191

Location of formation of periodic solar wind number density structures is discussed. Observation of proton and alpha anticorrelation in these structures [Viall et al., 2009] indicates that taking into account that bulk velocity of aplha-particles is higher than that of proton the place of formation for these structures should be located at distance less 0.002 AU from place of observation.Comment: 6 pages, submitted in GR

The psychological-type profile of clergywomen in ordained local ministry in the Church of England : pioneers or custodians?

This study employs psychological-type theory to compare the psychological profile of 144 clergywomen serving in ordained local ministry in the Church of England alongside the established profile of 237 professional mobile clergywomen serving in the Church of England published by Francis, Craig, Whinney, Tilley, and Slater. The data found no significant differences between these two groups of clergywomen in terms of orientations (introversion and extraversion) or in terms of the judging process (thinking and feeling). In terms of the perceiving process, there was a significantly higher proportion of sensing types among those serving in ordained local ministry (70% compared with 35%). In terms of the attitudes, there was a significantly higher proportion of judging types among those serving in ordained local ministry (83% compared with 65%). The combined sensing judging (SJ) temperament accounted for 65% of the clergywomen serving in ordained local ministry, compared with 29% of the clergywomen serving in professional mobile ministry in the earlier study. It is argued that the SJ temperament characterises a custodian style of ministry

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Liquid crystals and harmonic maps in polyhedral domains

Unit-vector fields \nvec on a convex polyhedron $P$ subject to tangent boundary conditions provide a simple model of nematic liquid crystals in prototype bistable displays. The equilibrium and metastable configurations correspond to minimisers and local minimisers of the Dirichlet energy, and may be regarded as $S^2$-valued harmonic maps on $P$. We consider unit-vector fields which are continuous away from the vertices of $P$. A lower bound for the infimum Dirichlet energy for a given homotopy class is obtained as a sum of minimal connections between fractional defects at the vertices of $P$. In certain cases, this lower bound can be improved by incorporating certain nonabelian homotopy invariants. For a rectangular prism, upper bounds for the infimum Dirichlet energy are obtained from locally conformal solutions of the Euler-Lagrange equations, with the ratio of the upper and lower bounds bounded independently of homotopy type. However, since the homotopy classes are not weakly closed, the infimum may not be realised; the existence and regularity properties of continuous local minimisers of given homotopy type are open questions. Numerical results suggest that some homotopy classes always contain smooth minimisers, while others may or may not depending on the geometry of $P$. Numerical results modelling a bistable device suggest that the observed nematic configurations may be distinguished topologically.Comment: 21 pages, 8 figures; in "Analysis and Stochastics of Growth Processes and Interface Models", P Morters et al. eds., Oxford University Press 2008, http://www.oup.com/uk/catalogue/?ci=978019923925

Moduli Stabilization and Cosmology of Type IIB on SU(2)-Structure Orientifolds

We consider type IIB flux compactifications on six-dimensional SU(2)-structure manifolds with O5- and O7-planes. These six-dimensional spaces allow not only for F_3 and H_3 fluxes but also for F_1 and F_5 fluxes. We derive the four-dimensional N=1 scalar potential for such compactifications and present one explicit example of a fully stabilized AdS vacuum with large volume and small string coupling. We then discuss cosmological aspects of these compactifications and derive several no-go theorems that forbid dS vacua and slow-roll inflation under certain conditions. We also study concrete examples of cosets and twisted tori and find that our no-go theorems forbid dS vacua and slow-roll inflation in all but one of them. For the latter we find a dS critical point with \epsilon numerically zero. However, the point has two tachyons and eta-parameter \eta \approx -3.1.Comment: 35 pages + appendices, LaTeX2e; v2: numerical dS extremum added, typos corrected, references adde

Dynamics of ferromagnetic domain walls under extreme fields

We report the existence of a new regime for domain wall motion in uniaxial and near-uniaxial ferromagnetic nanowires, characterised by applied magnetic fields sufficiently strong that one of the domains becomes unstable. There appears a new stable solution of the Landau-Lifshitz-Gilbert equation, describing a nonplanar domain wall moving with constant velocity and precessing with constant frequency. Even in the presence of thermal noise, the new solution can propagate for distances on the order of 500 times the field-free domain wall width before fluctuations in the unstable domain become appreciable.Comment: 7 pages, 5 figures (including Supplemental Material

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Liquid crystal defects in the Landau–de Gennes theory in two dimensions — Beyond the one-constant approximation

We consider the two-dimensional (2D) Landau–de Gennes energy with several elastic constants, subject to general k-radially symmetric boundary conditions. We show that for generic elastic constants the critical points consistent with the symmetry of the boundary conditions exist only in the case k = 2. In this case we identify three types of radial profiles: with two, three of full five components and numerically investigate their minimality and stability depending on suitable parametres. We also numerically study the stability properties of the critical points of the Landau–de Gennes energy and capture the intricate dependence of various qualitative features of these solutions on the elastic constants and the physical regimes of the liquid crystal system