Effects of Capping on the (Ga,Mn)As Magnetic Depth Profile

Annealing can increase the Curie temperature and net magnetization in uncapped (Ga,Mn)As films, effects that are suppressed when the films are capped with GaAs. Previous polarized neutron reflectometry (PNR) studies of uncapped (Ga,Mn)As revealed a pronounced magnetization gradient that was reduced after annealing. We have extended this study to (Ga,Mn)As capped with GaAs. We observe no increase in Curie temperature or net magnetization upon annealing. Furthermore, PNR measurements indicate that annealing produces minimal differences in the depth-dependent magnetization, as both as-grown and annealed films feature a significant magnetization gradient. These results suggest that the GaAs cap inhibits redistribution of interstitial Mn impurities during annealing.Comment: 12 pages, 3 figures, submitted to Applied Physics Letter

Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids—the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient mdx mice (Cmah−/−;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah−/−;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah−/−;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah−/−;mdx mice. Moreover, we show long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah−/−;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics

Superconducting Order Parameter Symmetry in Multi-layer Cuprates

We discuss the allowed order parameter symmetries in multi-layer cuprates and their physical consequences using highly non-specific forms of the inter- and intra-plane interactions. Within this framework, the bi-layer case is discussed in detail with particular attention paid to the role of small orthorhombic distortions as would derive from the chains in YBCO or superlattice effects in BSCCO. In the orthorhombic bi-layer case the (s,-s) state is of special interest, since for a wide range of parameters this state exhibits pi phase shifts in corner Josephson junction experiments. In addition, its transition temperature is found to be insensitive to non-magnetic inter-plane disorder, as would be present at the rare earth site in YBCO, for example. Of particular interest, also, are the role of van Hove singularities which are seen to stabilize states with d_{x^2 - y^2}-like symmetry, (as well as nodeless s-states) and to elongate the gap functions along the four van Hove points, thereby leading to a substantial region of gaplessness. We find that d_{x^2 - y^2}-like states are general solutions for repulsive interactions; they possess the fewest number of nodes and therefore the highest transition temperatures. In this way, they should not be specifically associated with a spin fluctuation driven pairing mechanism.Comment: REVTeX documentstyle, 34 pages, 10 figures include

Down syndrome-recent progress and future prospects

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS

Systematics of two-component superconductivity in YBa2Cu3O6.95YBa_{2}Cu_{3}O_{6.95} from microwave measurements of high quality single crystals

Systematic microwave surface impedance measurements of YBCO single crystals grown in $BaZrO_3$ crucibles reveal new properties that are not directly seen in similar measurements of other YBCO samples. Two key observations obtained from complex conductivity are: a new normal conductivity peak at around 80K and additional pairing below 65K. High pressure oxygenation of one of the crystals still yields the same results ruling out any effect of macroscopic segregation of O-deficient regions. A single complex order parameter cannot describe these data, and the results suggest at least two superconducting components. Comparisons with model calculations done for various decoupled two-component scenarios (i.e. s+d, d+d) are presented. Systematics of three single crystals show that the 80K quasiparticle peak is correlated with the normal state inelastic scattering rate. Close to Tc, the data follow a mean-field behavior. Overall, our results strongly suggest the presence of multiple pairing temperature and energy scales in $YBa_{2}Cu_{3}O_{6.95}$.Comment: 14 pages, 2-column, Revtex, 5 embedded postscript figures, uses graphicx. Postscript version also available at http://sagar.physics.neu.edu/preprints.htm

Critical Josephson Current in a Model Pb/YBa_2Cu_3O_7 Junction

In this article we consider a simple model for a c--axis Pb/YBa_2Cu_3O_{7-\delta} Josephson junction. The observation of a nonzero current in such a junction by Sun et al. [A. G. Sun, D. A. Gajewski, M. B. Maple, R. C. Dynes, Phys. Rev. Lett. 72, 2267 (1994)] has been taken as evidence against d--wave superconductivity in YBa_2Cu_3O_{7-\delta}. We suggest, however, that the pairing interaction in the CuO_2 planes may well be d--wave but that the CuO chains destroy the tetragonal symmetry of the system. We examine two ways in which this happens. In a simple model of an incoherent junction, the chains distort the superconducting condensate away from d_{x^2-y^2} symmetry. In a specular junction the chains destroy the tetragonal symmetry of the tunneling matrix element. In either case, the loss of tetragonal symmetry results in a finite Josephson current. Our calculated values of the critical current for specular junctions are in good agreement with the results of Sun and co-workers.Comment: Latex File, 21 pages, 6 figures in uuencoded postscript, In Press (Phys. Rev. B

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia

Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders in particular. Strong evidence (P=7.0 × 10−7) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample (N=1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression (N=1196) and schizophrenia (N=479) and UK non-psychiatric comparison groups (N=15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia (P=0.034) and recurrent major depression (P=0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data

Is Ankyrin a genetic risk factor for psychiatric phenotypes?

Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases