Superconducting proximity effects in metals with a repulsive pairing interaction

Studies of the superconducting proximity effect in normal conductor/superconductor $(N/S)$ junctions almost universally assume no effective electron-electron coupling in the $N$ region. While such an approximation leads to a simple description of the proximity effect, it is unclear how it could be rigorously justified. We reveal a much more complex picture of the proximity effect in $N/S$ bilayers, where $S$ is a clean s-wave BCS superconductor and $N$ is a simple metal with a repulsive effective electron coupling. We elucidate the proximity effect behavior using a highly accurate method to self-consistently solve the Bogoliubov-deGennes equations. We present our results for a wide range of values of the interface scattering, the Fermi wave vector mismatch, the temperature, and the ratio $g$ of the effective interaction strengths in the $N$ and $S$ region. We find that the repulsive interaction, represented by a negative $g$, strongly alters the signatures of the proximity effect as can be seen in the spatial dependence of the Cooper pair amplitude and the pair potential, as well as in the local density of states near the interface.Comment: 12 pages, including 10 figures. To appear in Phys. Rev.

Interleukin-1 inhibits glucose-induced Ca2+ uptake by islets of Langerhans

AbstractRecombinant interleukin-1 (rIL-1) is known to inhibit glucose-induced insulin secretion by islets of Langerhans, a novel target tissue of cytokine. We have investigated whether rIL-1 pretreatment affects biochemical mechanisms known to be involved in the regulation of Ca2+ homeostasis during glucose-induced insulin secretion. Glucose-induced Ca2+ uptake by intact islets through the plasma membrane was dramatically inhibited (96%) by rIL-1 (2 nM). rIL-1, however, did not affect Ca2+ uptake by, or Ins 1,4,5-P3-induced Ca2+ efflux from, the endoplasmic reticulum in digitonin-permeabilized islets, although glucose-induced accumulation of inositol trisphosphates was inhibited (38%). These results suggest that perturbation of intracellular Ca2+ homeostasis in islets is involved in inhibition of insulin secretion by rIL-1

Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle.

Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10-50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1-5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses

Linear combinations of docking affinities explain quantitative differences in RTK signaling

Receptor tyrosine kinases (RTKs) process extracellular cues by activating a broad array of signaling proteins. Paradoxically, they often use the same proteins to elicit diverse and even opposing phenotypic responses. Binary, ‘on–off' wiring diagrams are therefore inadequate to explain their differences. Here, we show that when six diverse RTKs are placed in the same cellular background, they activate many of the same proteins, but to different quantitative degrees. Additionally, we find that the relative phosphorylation levels of upstream signaling proteins can be accurately predicted using linear models that rely on combinations of receptor-docking affinities and that the docking sites for phosphoinositide 3-kinase (PI3K) and Shc1 provide much of the predictive information. In contrast, we find that the phosphorylation levels of downstream proteins cannot be predicted using linear models. Taken together, these results show that information processing by RTKs can be segmented into discrete upstream and downstream steps, suggesting that the challenging task of constructing mathematical models of RTK signaling can be parsed into separate and more manageable layers

PEDSnet: a National Pediatric Learning Health System

A learning health system (LHS) integrates research done in routine care settings, structured data capture during every encounter, and quality improvement processes to rapidly implement advances in new knowledge, all with active and meaningful patient participation. While disease-specific pediatric LHSs have shown tremendous impact on improved clinical outcomes, a national digital architecture to rapidly implement LHSs across multiple pediatric conditions does not exist. PEDSnet is a clinical data research network that provides the infrastructure to support a national pediatric LHS. A consortium consisting of PEDSnet, which includes eight academic medical centers, two existing disease-specific pediatric networks, and two national data partners form the initial partners in the National Pediatric Learning Health System (NPLHS). PEDSnet is implementing a flexible dual data architecture that incorporates two widely used data models and national terminology standards to support multi-institutional data integration, cohort discovery, and advanced analytics that enable rapid learning

Bailing Out the Milky Way: Variation in the Properties of Massive Dwarfs Among Galaxy-Sized Systems

Recent kinematical constraints on the internal densities of the Milky Way's dwarf satellites have revealed a discrepancy with the subhalo populations of simulated Galaxy-scale halos in the standard CDM model of hierarchical structure formation. This has been dubbed the "too big to fail" problem, with reference to the improbability of large and invisible companions existing in the Galactic environment. In this paper, we argue that both the Milky Way observations and simulated subhalos are consistent with the predictions of the standard model for structure formation. Specifically, we show that there is significant variation in the properties of subhalos among distinct host halos of fixed mass and suggest that this can reasonably account for the deficit of dense satellites in the Milky Way. We exploit well-tested analytic techniques to predict the properties in a large sample of distinct host halos with a variety of masses spanning the range expected of the Galactic halo. The analytic model produces subhalo populations consistent with both Via Lactea II and Aquarius, and our results suggest that natural variation in subhalo properties suffices to explain the discrepancy between Milky Way satellite kinematics and these numerical simulations. At least ~10% of Milky Way-sized halos host subhalo populations for which there is no "too big to fail" problem, even when the host halo mass is as large as M_host = 10^12.2 h^-1 M_sun. Follow-up studies consisting of high-resolution simulations of a large number of Milky Way-sized hosts are necessary to confirm our predictions. In the absence of such efforts, the "too big to fail" problem does not appear to be a significant challenge to the standard model of hierarchical formation. [abridged]Comment: 12 pages, 3 figures; accepted by JCAP. Replaced with published versio

Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans.

BACKGROUND: Common genetic variation at genes that are imprinted and exclusively maternally expressed could explain the apparent maternal-specific inheritance of low birthweight reported in large family pedigrees. We identified ten single nucleotide polymorphisms (SNPs) in H19, and we genotyped three of these SNPs in families from the contemporary ALSPAC UK birth cohort (1,696 children, 822 mothers and 661 fathers) in order to explore associations with size at birth and cord blood IGF-II levels. RESULTS: Both offspring's and mother's H19 2992C>T SNP genotypes showed associations with offspring birthweight (P = 0.03 to P = 0.003) and mother's genotype was also associated with cord blood IGF-II levels (P = 0.0003 to P = 0.0001). The offspring genotype association with birthweight was independent of mother's genotype (P = 0.01 to P = 0.007). However, mother's untransmitted H19 2992T allele was also associated with larger birthweight (P = 0.04) and higher cord blood IGF-II levels (P = 0.002), suggesting a direct effect of mother's genotype on placental IGF-II expression and fetal growth. The association between mother's untransmitted allele and cord blood IGF-II levels was more apparent in offspring of first pregnancies than subsequent pregnancies (P-interaction = 0.03). Study of the independent Cambridge birth cohort with available DNA in mothers (N = 646) provided additional support for mother's H19 2992 genotype associations with birthweight (P = 0.04) and with mother's glucose levels (P = 0.01) in first pregnancies. CONCLUSION: The common H19 2992T allele, in the mother or offspring or both, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain, that are more evident among mother's smaller first-born infants.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Structural characterization and directed evolution of a novel acetyl xylan esterase reveals thermostability determinants of the carbohydrate esterase 7 family

Please read abstract in the article.The South Africa Bio-catalysis Initiative, Department of Science and Technology, the University of Pretoria Genomics Research Institute (D.A.C. and T.P.M.), the National Research Foundation (W.-D.S. and B.T.S.), the Research Development Program (T.P.M. and S.V.), and the Organization for Women in Science in the Developing World (OWSD) (F.A.A.).http://aem.asm.org2018-10-01hj2018BiochemistryGenetic

Manipulating ultracold atoms with a reconfigurable nanomagnetic system of domain walls

The divide between the realms of atomic-scale quantum particles and lithographically-defined nanostructures is rapidly being bridged. Hybrid quantum systems comprising ultracold gas-phase atoms and substrate-bound devices already offer exciting prospects for quantum sensors, quantum information and quantum control. Ideally, such devices should be scalable, versatile and support quantum interactions with long coherence times. Fulfilling these criteria is extremely challenging as it demands a stable and tractable interface between two disparate regimes. Here we demonstrate an architecture for atomic control based on domain walls (DWs) in planar magnetic nanowires that provides a tunable atomic interaction, manifested experimentally as the reflection of ultracold atoms from a nanowire array. We exploit the magnetic reconfigurability of the nanowires to quickly and remotely tune the interaction with high reliability. This proof-of-principle study shows the practicability of more elaborate atom chips based on magnetic nanowires being used to perform atom optics on the nanometre scale.Comment: 4 pages, 4 figure