Ferromagnetic Semiconductors: Moving Beyond (Ga,Mn)As

The recent development of MBE techniques for growth of III-V ferromagnetic semiconductors has created materials with exceptional promise in spintronics, i.e. electronics that exploit carrier spin polarization. Among the most carefully studied of these materials is (Ga,Mn)As, in which meticulous optimization of growth techniques has led to reproducible materials properties and ferromagnetic transition temperatures well above 150 K. We review progress in the understanding of this particular material and efforts to address ferromagnetic semiconductors as a class. We then discuss proposals for how these materials might find applications in spintronics. Finally, we propose criteria that can be used to judge the potential utility of newly discovered ferromagnetic semiconductors, and we suggest guidelines that may be helpful in shaping the search for the ideal material.Comment: 37 pages, 4 figure

Multi-model evaluation of the sensitivity of the global energy budget and hydrological cycle to resolution

This study undertakes a multi-model comparison with the aim to describe and quantify systematic changes of the global energy and water budgets when the horizontal resolution of atmospheric models is increased and to identify common factors of these changes among models. To do so, we analyse an ensemble of twelve atmosphere-only and six coupled GCMs, with different model formulations and with resolutions spanning those of state-of-the-art coupled GCMs, i.e. from resolutions coarser than 100 km to resolutions finer than 25 km. The main changes in the global energy budget with resolution are a systematic increase in outgoing longwave radiation and decrease in outgoing shortwave radiation due to changes in cloud properties, and a systematic increase in surface latent heat flux; when resolution is increased from 100 to 25 km, the magnitude of the change of those fluxes can be as large as 5 W m−2. Moreover, all but one atmosphere-only model simulate a decrease of the poleward energy transport at higher resolution, mainly explained by a reduction of the equator-to-pole tropospheric temperature gradient. Regarding hydrological processes, our results are the following: (1) there is an increase of global precipitation with increasing resolution in all models (up to 40 × 103 km3 year−1) but the partitioning between land and ocean varies among models; (2) the fraction of total precipitation that falls on land is on average 10% larger at higher resolution in grid point models, but it is smaller at higher resolution in spectral models; (3) grid points models simulate an increase of the fraction of land precipitation due to moisture convergence twice as large as in spectral models; (4) grid point models, which have a better resolved orography, show an increase of orographic precipitation of up to 13 × 103 km3 year−1 which explains most of the change in land precipitation; (5) at the regional scale, precipitation pattern and amplitude are improved with increased resolution due to a better simulated seasonal mean circulation. We discuss our results against several observational estimates of the Earth's energy budget and hydrological cycle and show that they support recent high estimates of global precipitation

The resolution sensitivity of the Asian summer monsoon and its inter-model comparison between MRI-AGCM and MetUM

In this study, we compare the resolution sensitivity of the Asian Summer Monsoon (ASM) in two Atmospheric General Circulation Models (AGCMs): the MRI-AGCM and the MetUM. We analyze the MetUM at three different resolutions, N96 (approximately 200-km mesh on the equator), N216 (90-km mesh) and N512 (40-km mesh), and the MRI-AGCM at TL95 (approximately 180-km mesh on the equator), TL319 (60-km mesh), and TL959 (20-km mesh). The MRI-AGCM and the MetUM both show decreasing precipitation over the western Pacific with increasing resolution, but their precipitation responses differ over the Indian Ocean. In MRI-AGCM, a large precipitation increase appears off the equator (5–20°N). In MetUM, this off-equatorial precipitation increase is less significant and precipitation decreases over the equator. Moisture budget analysis demonstrates that a changing in moisture flux convergence at higher resolution is related to the precipitation response. Orographic effects, intra-seasonal variability and the representation of the meridional thermal gradient are explored as possible causes of the resolution sensitivity. Both high-resolution AGCMs (TL959 and N512) can represent steep topography, which anchors the rainfall pattern over south Asia and the Maritime Continent. In MRI-AGCM, representation of low pressure systems in TL959 also contributes to the rainfall pattern. Furthermore, the seasonal evolution of the meridional thermal gradient appears to be more accurate at higher resolution, particularly in the MRI-AGCM. These findings emphasize that the impact of resolution is only robust across the two AGCMs for some features of the ASM, and highlights the importance of multi-model studies of GCM resolution sensitivity

Class IA PI3Kinase Regulatory Subunit, p85α, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

<p>Abstract</p> <p>Background</p> <p>Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.</p> <p>Presentation of the hypothesis</p> <p>Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.</p> <p>Testing and implications of the hypothesis</p> <p>Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.</p

Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila

<p>Abstract</p> <p>Background</p> <p>In male <it>Drosophila melanogaster</it>, the male specific lethal (MSL) complex is somehow responsible for a two-fold increase in transcription of most X-linked genes, which are enriched for histone H4 acetylated at lysine 16 (H4K16ac). This acetylation requires MOF, a histone acetyltransferase that is a component of the MSL complex. MOF also associates with the non-specific lethal or NSL complex. The MSL complex is bound within active genes on the male X chromosome with a 3' bias. In contrast, the NSL complex is enriched at promoter regions of many autosomal and X-linked genes in both sexes. In this study we have investigated the role of MOF as a transcriptional activator.</p> <p>Results</p> <p>MOF was fused to the DNA binding domain of Gal4 and targeted to the promoter region of UAS-reporter genes in <it>Drosophila</it>. We found that expression of a UAS-red fluorescent protein (DsRed) reporter gene was strongly induced by Gal4-MOF. However, DsRed RNA levels were about seven times higher in female than male larvae. Immunostaining of polytene chromosomes showed that Gal4-MOF co-localized with MSL1 to many sites on the X chromosome in male but not female nuclei. However, in female nuclei that express MSL2, Gal4-MOF co-localized with MSL1 to many sites on polytene chromosomes but DsRed expression was reduced. Mutation of conserved active site residues in MOF (Glu714 and Cys680) reduced HAT activity <it>in vitro </it>and UAS-DsRed activation in <it>Drosophila</it>. In the presence of Gal4-MOF, H4K16ac levels were enriched over UAS-<it>lacZ </it>and UAS-<it>arm-lacZ </it>reporter genes. The latter utilizes the constitutive promoter from the <it>arm </it>gene to drive <it>lacZ </it>expression. In contrast to the strong induction of UAS-DsRed expression, UAS-<it>arm-lacZ </it>expression increased by about 2-fold in both sexes.</p> <p>Conclusions</p> <p>Targeting MOF to reporter genes led to transcription enhancement and acetylation of histone H4 at lysine 16. Histone acetyltransferase activity was required for the full transcriptional response. Incorporation of Gal4-MOF into the MSL complex in males led to a lower transcription enhancement of UAS-<it>DsRed </it>but not UAS-<it>arm-lacZ </it>genes. We discuss how association of Gal4-MOF with the MSL or NSL proteins could explain our results.</p

Become the best coach you can be: the role of coach training and coaching experience in workplace coaching quality and quality control

This paper explores whether coach training or coaching experience leads to better coaching quality and quality control. In two large studies, both coaches (N1 = 2267) and personnel managers who book coaches for their company (N2 = 754) answered questions about coaching quality and quality control. The results show that more coach training leads to not only a better self-perceived coaching quality (Study 1) but also a better other-perceived coaching-quality (Study 2); moreover, more coach training positively affects quality control. It is remarkable that coaching experience showed no significant relation regarding other-perceived coaching quality and quality control. Study 2 further revealed that references lead to more recommendations but not to a better coaching quality or quality control. Thus, coach training is an essential factor when selecting organizational coaches. Further research is needed to understand the impact of different approaches to coach trainings on coaching outcomes

rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants

The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC

Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the host following an acute infection. Reactivation from latency contributes to the development of KSHV-induced malignancies, which include Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients, primary effusion lymphoma and multicentric Castleman's disease. However, the physiological cues that trigger KSHV reactivation remain unclear. Here, we show that the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces KSHV reactivation from latency through both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic replication, and KSHV reactivation from latency induced by oxidative stress, hypoxia, and proinflammatory and proangiogenic cytokines are mediated by H2O2. Mechanistically, H2O2 induction of KSHV reactivation depends on the activation of mitogen-activated protein kinase ERK1/2, JNK, and p38 pathways. Significantly, H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase and glutathione inhibit KSHV lytic replication in culture. In a mouse model of KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and significantly prolongs the lifespan of the mice. These results directly relate KSHV reactivation to oxidative stress and inflammation, which are physiological hallmarks of KS patients. The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents for effectively targeting KSHV replication and KSHV-related malignancies