High field magneto-transport in high mobility gated InSb/InAlSb quantum well heterostructures

We present high field magneto-transport data from a range of 30nm wide InSb/InAlSb quantum wells. The low temperature carrier mobility of the samples studied ranged from 18.4 to 39.5 m2V-1s-1 with carrier densities between 1.5x1015 and 3.28x1015 m-2. Room temperature mobilities are reported in excess of 6 m2V-1s-1. It is found that the Landau level broadening decreases with carrier density and beating patterns are observed in the magnetoresistance with non-zero node amplitudes in samples with the narrowest broadening despite the presence of a large g-factor. The beating is attributed to Rashba splitting phenomenon and Rashba coupling parameters are extracted from the difference in spin populations for a range of samples and gate biases. The influence of Landau level broadening and spin-dependent scattering rates on the observation of beating in the Shubnikov-de Haas oscillations is investigated by simulations of the magnetoconductance. Data with non-zero beat node amplitudes are accompanied by asymmetric peaks in the Fourier transform, which are successfully reproduced by introducing a spin-dependent broadening in the simulations. It is found that the low-energy (majority) spin up state suffers more scattering than the high-energy (minority) spin down state and that the absence of beating patterns in the majority of (lower density) samples can be attributed to the same effect when the magnitude of the level broadening is large

Evidence for Nodal superconductivity in Sr2_{2}ScFePO3_{3}

Point contact Andreev reflection spectra have been taken as a function of temperature and magnetic field on the polycrystalline form of the newly discovered iron-based superconductor Sr2ScFePO3. A zero bias conductance peak which disappears at the superconducting transition temperature, dominates all of the spectra. Data taken in high magnetic fields show that this feature survives until 7T at 2K and a flattening of the feature is observed in some contacts. Here we inspect whether these observations can be interpreted within a d-wave, or nodal order parameter framework which would be consistent with the recent theoretical model where the height of the P in the Fe-P-Fe plane is key to the symmetry of the superconductivity. However, in polycrystalline samples care must be taken when examining Andreev spectra to eliminate or take into account artefacts associated with the possible effects of Josephson junctions and random alignment of grains.Comment: Published versio

Interrupting Antiretroviral Treatment in HIV Cure Research: Scientific and Ethical Considerations

Over the past several years there has been intense activity directed at the possibility of achieving remission or eradication of HIV infection. Current assays for the measurement of latent HIV are insufficient to demonstrate complete clearance of replication-competent HIV. Therefore, the ultimate test for assessing whether investigational interventions have resulted in HIV remission or eradication is to interrupt standard antiretroviral therapy (ART) in a carefully controlled clinical trial setting. These procedures, known as analytic treatment interruptions (ATIs), raise important scientific and ethical questions. The lack of definitive assays for measuring viral reservoirs not only makes research on HIV remission or cure challenging, it also affects the ability to assess risks from ATIs themselves. In spite of these challenges, basic ethical criteria can be met with careful study design and close monitoring. In this brief report we outline ethical standards for HIV cure research involving ATIs. These criteria should be revisited as the science evolves

Room temperature ballistic transport in InSb quantum well nanodevices

We report the room temperature observation of significant ballistic electron transport in shallow etched four-terminal mesoscopic devices fabricated on an InSb/AlInSb quantum well (QW) heterostructure with a crucial partitioned growth-buffer scheme. Ballistic electron transport is evidenced by a negative bend resistance signature which is quite clearly observed at 295 K and at current densities in excess of 10$^{6}$ A/cm$^{2}$. This demonstrates unequivocally that by using effective growth and processing strategies, room temperature ballistic effects can be exploited in InSb/AlInSb QWs at practical device dimensions

The miR-17 similar to 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma

Medulloblastomas (MBs) are the most common brain tumors in children. Some are thought to originate from cerebellar granule neuron progenitors (GNPs) that fail to undergo normal cell cycle exit and differentiation. Because microRNAs regulate numerous aspects of cellular physiology and development, we reasoned that alterations in miRNA expression might contribute to MB. We tested this hypothesis using 2 spontaneous mouse MB models with specific initiating mutations, Ink4c(-/-); Ptch1(+/-) and Ink4c(-/-); p53(-/-). We found that 26 miRNAs showed increased expression and 24 miRNAs showed decreased expression in proliferating mouse GNPs and MBs relative to mature mouse cerebellum, regardless of genotype. Among the 26 overexpressed miRNAs, 9 were encoded by the miR-17 similar to 92 cluster family, a group of microRNAs implicated as oncogenes in several tumor types. Analysis of human MBs demonstrated that 3 miR-17 similar to 92 cluster miRNAs (miR-92, miR-19a, and miR-20) were also overexpressed in human MBs with a constitutively activated Sonic Hedgehog (SHH) signaling pathway, but not in other forms of the disease. To test whether the miR-17 similar to 92 cluster could promote MB formation, we enforced expression of these miRNAs in GNPs isolated from cerebella of postnatal (P) day P6 Ink4c(-/-); Ptch1(+/-) mice. These, but not similarly engineered cells from Ink4c(-/-); p53(-/-) mice, formed MBs in orthotopic transplants with complete penetrance. Interestingly, orthotopic mouse tumors ectopically expressing miR-17 similar to 92 lost expression of the wild-type Ptch1 allele. Our findings suggest a functional collaboration between the miR-17 similar to 92 cluster and the SHH signaling pathway in the development of MBs in mouse and man

Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre

Systemic amyloidosis is a serious disease which is caused when normal circulating proteins misfold and aggregate extracellularly as insoluble fibrillary deposits throughout the body. This commonly results in cardiac, renal and neurological damage. The tissue target, progression and outcome of the disease depends on the type of protein forming the fibril deposit, and its correct identification is central to determining therapy. Proteomics is now used routinely in our centre to type amyloid; over the past 7 years we have examined over 2000 clinical samples. Proteomics results are linked directly to our patient database using a simple algorithm to automatically highlight the most likely amyloidogenic protein. Whilst the approach has proved very successful, we have encountered a number of challenges, including poor sample recovery, limited enzymatic digestion, the presence of multiple amyloidogenic proteins and the identification of pathogenic variants. Our proteomics procedures and approaches to resolving difficult issues are outlined

The Migration of Elites in a Borderless World: Citizenship as an Incentive for Professionals and Managers?

Der Artikel geht der Frage nach, inwiefern die geöffneten Türen für die Immigration Hochqualifizierter in den OECD-Ländern tatsächlich zu einer verstärkten Migrationsbewegung führen. Die Analyse von Daten zu Eliten- und Hochqualifiziertenmigration in Ostasien, Europa und den USA führt zu dem Ergebnis, dass diese dem Muster einer „brain circulation“ folgt und die Staatsbürgerrechte dabei keine entscheidende Rolle spielen

Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression

OBJECTIVES: The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM). BACKGROUND: Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain. METHODS: Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a "TTR-stabilizing" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results. RESULTS: Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%). CONCLUSIONS: Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran

Change in N-terminal pro-B-type natriuretic peptide at 1 year predicts mortality in wild-type transthyretin amyloid cardiomyopathy

OBJECTIVES: Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive and fatal condition. Although prognosis can be determined at the time of diagnosis according to National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage, the clinical course varies substantially between individuals. There are currently no established measures of rate of disease progression. Through systematic analysis of functional, biochemical and echocardiographic disease-related variables we aimed to identify prognostic markers of disease progression in wtATTR-CM. METHODS: This is a retrospective observational study of 432 patients with wtATTR-CM diagnosed at the UK NAC, none of whom received disease-modifying therapy. The association between mortality from the 12-month timepoint and change from diagnosis to 12 months in a variety of disease-related variables was explored using Cox regression. RESULTS: Change in N-terminal pro-B-type natriuretic peptide concentration (∆ NT-proBNP) at 12 months from diagnosis was the strongest predictor of ongoing mortality and was independent of both change in other disease-related variables (HR 1.04 per 500 ng/L increase (95% CI 1.01 to 1.07); p=0.003) and a range of known prognostic variables at the time of diagnosis (HR 1.07 per 500 ng/L increase (95% CI 1.02 to 1.13); p=0.007). An increase in NT-proBNP of >500 ng/L, >1000 ng/L and >2000 ng/L during the first year of follow-up occurred in 45%, 35% and 16% of patients, respectively. CONCLUSION: Change in NT-proBNP concentration during the first year of follow-up is a powerful independent predictor of mortality in wtATTR-CM

Zero-field spin-splitting and spin lifetime in n-InSb/In1-xAlxSb asymmetric quantum well heterostructures

The spin-orbit (SO) coupling parameters for lowest conduction subband due to structural (SIA) and bulk (BIA) inversion asymmetry are calculated for a range of carrier densities in [001]-grown delta-doped n-type InSb/In1-xAlxSb asymmetric quantum wells using the established 8 band k.p formalism [PRB 59,8 R5312 (1999)]. We present calculations for conditions of zero bias at 10 K. It is shown that both the SIA and BIA parameters scale approximately linearly with carrier density, and exhibit a marked dependence on well width when alloy composition is adjusted to allow maximum upper barrier height for a given well width. In contrast to other material systems the BIA contribution to spin splitting is found to be of significant and comparable value to the SIA mechanism in these structures. We calculate the spin lifetime for spins oriented along [11-0] based on D'yakonov-Perel mechanism using both the theory of Averkiev et al. [J. Phys.:Condens. Matter 14 (2002)] and also the rate of precession of spins about the effective magnetic field, taking into account all three SO couplings, showing good agreement.Spin lifeime for this direction is largest in the narrow wells over the range of moderate carrier densities considered, which is attributed to the reduced magnitude of the k-cubic BIA parameter in narrow wells. The inherently large BIA induced SO coupling in these systems is shown to have considerable effect on the spin lifetime, which exhibits significant reduction in the maximum spin lifetime compared to previous studies which consider systems with relatively weak BIA induced SO coupling. The relaxation rate of spins oriented in the [001] direction is dominated by the k-linear SIA and BIA coupling parameters and at least an order of magnitude greater than in the [11-0] direction.Comment: 18 pages 12 figure