1,063 research outputs found
Oxide Heterostructures from a Realistic Many-Body Perspective
Oxide heterostructures are a new class of materials by design, that open the
possibility for engineering challenging electronic properties, in particular
correlation effects beyond an effective single-particle description. This short
review tries to highlight some of the demanding aspects and questions,
motivated by the goal to describe the encountered physics from first
principles. The state-of-the-art methodology to approach realistic many-body
effects in strongly correlated oxides, the combination of density functional
theory with dynamical mean-field theory, will be briefly introduced. Discussed
examples deal with prominent Mott-band- and band-band-insulating type of oxide
heterostructures, where different electronic characteristics may be stabilized
within a single architectured oxide material.Comment: 19 pages, 9 figure
Hubble Space Telescope Imaging of Lyman Alpha Emission at z=4.4
We present the highest redshift detections of resolved Lyman alpha emission,
using Hubble Space Telescope/ACS F658N narrowband-imaging data taken in
parallel with the Wide Field Camera 3 Early Release Science program in the
GOODS CDF-S. We detect Lyman alpha emission from three spectroscopically
confirmed z = 4.4 Lyman alpha emitting galaxies (LAEs), more than doubling the
sample of LAEs with resolved Lyman alpha emission. Comparing the light
distribution between the rest-frame ultraviolet continuum and narrowband
images, we investigate the escape of Lyman alpha photons at high redshift.
While our data do not support a positional offset between the Lyman alpha and
rest-frame ultraviolet (UV) continuum emission, the half-light radii in two out
of the three galaxies are significantly larger in Lyman alpha than in the
rest-frame UV continuum. This result is confirmed when comparing object sizes
in a stack of all objects in both bands. Additionally, the narrowband flux
detected with HST is significantly less than observed in similar filters from
the ground. These results together imply that the Lyman alpha emission is not
strictly confined to its indigenous star-forming regions. Rather, the Lyman
alpha emission is more extended, with the missing HST flux likely existing in a
diffuse outer halo. This suggests that the radiative transfer of Lyman alpha
photons in high-redshift LAEs is complicated, with the interstellar-medium
geometry and/or outflows playing a significant role in galaxies at these
redshifts.Comment: Submitted to the Astrophysical Journal. 11 pages, 10 figure
Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study
Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and colleagues (Beach). All of these systems use semi-quantitative scoring (4- or 5-tier scales) of Lewy pathology (LP; i.e., Lewy bodies and Lewy neurites) in defined cortical and subcortical areas. While these systems are widely used, some suffer from low inter-rater reliability and/or an inability to unequivocally classify all cases with LP. To address these limitations, we devised a new system, the LP consensus criteria (LPC), which is based on the McKeith system, but applies a dichotomous approach for the scoring of LP (i.e., “absent” vs. “present”) and includes amygdala-predominant and olfactory-only stages. α-Synuclein-stained slides from brainstem, limbic system, neocortex, and olfactory bulb from a total of 34 cases with LP provided by the Newcastle Brain Tissue Resource (NBTR) and the University of Pennsylvania brain bank (UPBB) were scanned and assessed by 16 raters, who provided diagnostic categories for each case according to Braak, McKeith, Leverenz, Beach, and LPC systems. In addition, using LP scores available from neuropathological reports of LP cases from UPBB (n = 202) and NBTR (n = 134), JT (UPBB) and JA (NBTR) assigned categories according to all staging systems to these cases. McKeith, Leverenz, and LPC systems reached good (Krippendorff’s α ≈ 0.6), while both Braak and Beach systems had lower (Krippendorff’s α ≈ 0.4) inter-rater reliability, respectively. Using the LPC system, all cases could be unequivocally classified by the majority of raters, which was also seen for 97.1% when the Beach system was used. However, a considerable proportion of cases could not be classified when using Leverenz (11.8%), McKeith (26.5%), or Braak (29.4%) systems. The category of neocortical LP according to the LPC system was associated with a 5.9 OR (p < 0.0001) of dementia in the 134 NBTR cases and a 3.14 OR (p = 0.0001) in the 202 UPBB cases. We established that the LPC system has good reproducibility and allows classification of all cases into distinct categories. We expect that it will be reliable and useful in routine diagnostic practice and, therefore, suggest that it should be the standard future approach for the basic post-mortem evaluation of LP
Hubble Space Telescope WFC3 Early Release Science: Emission-Line Galaxies from Infrared Grism Observations
We present grism spectra of emission-line galaxies (ELGs) from 0.6-1.6
microns from the Wide Field Camera 3 on the Hubble Space Telescope. These new
infrared grism data augment previous optical Advanced Camera for Surveys G800L
0.6-0.95 micron grism data in GOODS-South from the PEARS program, extending the
wavelength covereage well past the G800L red cutoff. The ERS grism field was
observed at a depth of 2 orbits per grism, yielding spectra of hundreds of
faint objects, a subset of which are presented here. ELGs are studied via the
Ha, [OIII], and [OII] emission lines detected in the redshift ranges 0.2<z<1.4,
1.2<z<2.2 and 2.0<z<3.3 respectively in the G102 (0.8-1.1 microns; R~210) and
G141 (1.1-1.6 microns; R~130) grisms. The higher spectral resolution afforded
by the WFC3 grisms also reveals emission lines not detectable with the G800L
grism (e.g., [SII] and [SIII] lines). From these relatively shallow
observations, line luminosities, star-formation rates, and grism spectroscopic
redshifts are determined for a total of 48 ELGs to m(AB)~25 mag. Seventeen
GOODS-South galaxies that previously only had photometric redshifts now have
new grism-spectroscopic redshifts, in some cases with large corrections to the
photometric redshifts (Delta(z)~0.3-0.5). Additionally, one galaxy had no
previously-measured redshift but now has a secure grism-spectroscopic redshift,
for a total of 18 new GOODS-South spectroscopic redshifts. The faintest source
in our sample has a magnitude m(AB)=26.9 mag. The ERS grism data also reflect
the expected trend of lower specific star formation rates for the highest mass
galaxies in the sample as a function of redshift, consistent with downsizing
and discovered previously from large surveys. These results demonstrate the
remarkable efficiency and capability of the WFC3 NIR grisms for measuring
galaxy properties to faint magnitudes and redshifts to z>2.Comment: Accepted for publication in AJ. Updated to include referee comments.
Updated sample using improved reduction contains 23 new galaxies (Table 1;
Figures 2 & 3
Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems
A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud
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Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection:protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales
IntroductionSARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs.Methods and analysisWe will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection.Ethics and disseminationThis study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway
The Hubble Space Telescope Wide Field Camera 3 Early Release Science data: Panchromatic Faint Object Counts for 0.2-2 microns wavelength
We describe the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) Early
Release Science (ERS) observations in the Great Observatories Origins Deep
Survey (GOODS) South field. The new WFC3 ERS data provide calibrated, drizzled
mosaics in the UV filters F225W, F275W, and F336W, as well as in the near-IR
filters F098M (Ys), F125W (J), and F160W (H) with 1-2 HST orbits per filter.
Together with the existing HST Advanced Camera for Surveys (ACS) GOODS-South
mosaics in the BViz filters, these panchromatic 10-band ERS data cover 40-50
square arcmin at 0.2-1.7 {\mu}m in wavelength at 0.07-0.15" FWHM resolution and
0.090" Multidrizzled pixels to depths of AB\simeq 26.0-27.0 mag (5-{\sigma})
for point sources, and AB\simeq 25.5-26.5 mag for compact galaxies.
In this paper, we describe: a) the scientific rationale, and the data taking
plus reduction procedures of the panchromatic 10-band ERS mosaics; b) the
procedure of generating object catalogs across the 10 different ERS filters,
and the specific star-galaxy separation techniques used; and c) the reliability
and completeness of the object catalogs from the WFC3 ERS mosaics. The
excellent 0.07-0.15" FWHM resolution of HST/WFC3 and ACS makes star- galaxy
separation straightforward over a factor of 10 in wavelength to AB\simeq 25-26
mag from the UV to the near-IR, respectively.Comment: 51 pages, 71 figures Accepted to ApJS 2011.01.2
Reduced Expression of IFIH1 Is Protective for Type 1 Diabetes
IFIH1 (interferon induced with helicase C domain 1), also known as MDA5 (melanoma differentiation-associated protein 5), is one of a family of intracellular proteins known to recognise viral RNA and mediate the innate immune response. IFIH1 is causal in type 1 diabetes based on the protective associations of four rare variants, where the derived alleles are predicted to reduce gene expression or function. Originally, however, T1D protection was mapped to the common IFIH1 nsSNP, rs1990760 or Thr946Ala. This common amino acid substitution does not cause a loss of function and evidence suggests the protective allele, Ala946, may mark a haplotype with reduced expression of IFIH1 in line with the protection conferred by the four rare loss of function alleles. We have performed allele specific expression analysis that supports this hypothesis: the T1D protective haplotype correlates with reduced IFIH1 transcription in interferon-β stimulated peripheral blood mononuclear cells (overall p = 0.012). In addition, we have used multiflow cytometry analysis and quantitative PCR assays to prove reduced expression of IFIH1 in individuals heterozygous for three of the T1D-associated rare alleles: a premature stop codon, rs35744605 (Glu627X) and predicted splice variants, rs35337543 (IVS8+1) and rs35732034 (IVS14+1). We also show that the nsSNP, Ile923V, does not alter pre-mRNA levels of IFIH1. These results confirm and extend the new autoimmune disease pathway of reduced IFIH1 expression and protein function protecting from T1D
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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