The goal of early autism screening is earlier treatment. We pilot-tested a 12-week, low-intensity treatment with seven symptomatic infants ages 7–15 months. Parents mastered the intervention and ...maintained skills after treatment ended. Four comparison groups were matched from a study of infant siblings. The treated group of infants was significantly more symptomatic than most of the comparison groups at 9 months of age but was significantly less symptomatic than the two most affected groups between 18 and 36 months. At 36 months, the treated group had much lower rates of both ASD and DQs under 70 than a similarly symptomatic group who did not enroll in the treatment study. It appears feasible to identify and enroll symptomatic infants in parent-implemented intervention before 12 months, and the pilot study outcomes are promising, but testing the treatment’s efficacy awaits a randomized trial.
Antiferromagnets are hard to control by external magnetic fields because of the alternating directions of magnetic moments on individual atoms and the resulting zero net magnetization. However, ...relativistic quantum mechanics allows for generating current-induced internal fields whose sign alternates with the periodicity of the antiferromagnetic lattice. Using these fields, which couple strongly to the antiferromagnetic order, we demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 10⁶ ampere per square centimeter. Electrical writing is combined in our solid-state memory with electrical readout and the stored magnetic state is insensitive to and produces no external magnetic field perturbations, which illustrates the unique merits of antiferromagnets for spintronics.
We present ground-based and Swift photometric and spectroscopic observations of the candidate tidal disruption event (TDE) ASASSN-14li, found at the centre of PGC 043234 (d ... 90 Mpc) by the All-Sky ...Automated Survey for SuperNovae (ASAS-SN). The source had a peak bolometric luminosity of ... and a total integrated energy of ... erg radiated over the ~6 months of observations presented. The UV/optical emission of the source is well fitted by a blackbody with roughly constant temperature of T ... 35,000 K, while the luminosity declines by roughly a factor of 16 over this time. The optical/UV luminosity decline is broadly consistent with an exponential decline, ..., with t0 ... 60 d. ASASSN-14li also exhibits soft X-ray emission comparable in luminosity to the optical and UV emission but declining at a slower rate, and the X-ray emission now dominates. Spectra of the source show broad Balmer and helium lines in emission as well as strong blue continuum emission at all epochs. We use the discoveries of ASASSN-14li and ASASSN-14ae to estimate the TDE rate implied by ASAS-SN, finding an average rate of ... per galaxy with a 90 per cent confidence interval of ... per galaxy. ASAS-SN found roughly 1 TDE for every 70 Type Ia supernovae in 2014, a rate that is much higher than that of other surveys. (ProQuest: ... denotes formulae/symbols omitted.)
We report on nano-infrared (IR) imaging studies of confined plasmon modes inside patterned graphene nanoribbons (GNRs) fabricated with high-quality chemical-vapor-deposited (CVD) graphene on Al2O3 ...substrates. The confined geometry of these ribbons leads to distinct mode patterns and strong field enhancement, both of which evolve systematically with the ribbon width. In addition, spectroscopic nanoimaging in the mid-infrared range 850–1450 cm–1 allowed us to evaluate the effect of the substrate phonons on the plasmon damping. Furthermore, we observed edge plasmons: peculiar one-dimensional modes propagating strictly along the edges of our patterned graphene nanostructures.
Understanding natural climate variability and its driving factors is crucial to assessing future climate change. Therefore, comparing proxy-based climate reconstructions with forcing factors as well ...as comparing these with paleoclimate model simulations is key to gaining insights into the relative roles of internal versus forced variability. A review of the state of modelling of the climate of the last millennium prior to the CMIP5-PMIP3 (Coupled Model Intercomparison Project Phase 5-Paleoclimate Modelling Intercomparison Project Phase 3) coordinated effort is presented and compared to the available temperature reconstructions. Simulations and reconstructions broadly agree on reproducing the major temperature changes and suggest an overall linear response to external forcing on multidecadal or longer timescales. Internal variability is found to have an important influence at hemispheric and global scales. The spatial distribution of simulated temperature changes during the transition from the Medieval Climate Anomaly to the Little Ice Age disagrees with that found in the reconstructions. Thus, either internal variability is a possible major player in shaping temperature changes through the millennium or the model simulations have problems realistically representing the response pattern to external forcing. A last millennium transient climate response (LMTCR) is defined to provide a quantitative framework for analysing the consistency between simulated and reconstructed climate. Beyond an overall agreement between simulated and reconstructed LMTCR ranges, this analysis is able to single out specific discrepancies between some reconstructions and the ensemble of simulations. The disagreement is found in the cases where the reconstructions show reduced covariability with external forcings or when they present high rates of temperature change.
Iron replacement therapy is a common treatment in patients with anaemia and Crohn's disease, but oral iron supplements are less tolerated. The pathogenesis of Crohn's disease is attributed to ...intestinal bacteria and environmental factors that trigger disease in a genetically predisposed host. The aim of this study was to characterise the interrelationship between luminal iron sulfate, systemic iron, the gut microbiota and the development of chronic ileitis in a murine model of Crohn's disease.
Wild type (WT) and heterozygous TNF(ΔARE/WT) mice were fed with an iron sulfate containing or iron sulfate free diet in combination with intraperitoneal control injections or iron injections for 11 weeks.
TNF(ΔARE/WT) mice develop severe inflammation of the distal ileum but remained completely healthy when transferred to an iron sulfate free diet, even if iron was systemically repleted. Absence of luminal iron sulfate reduced cellular markers of endoplasmic reticulum (ER) stress responses and pro-apoptotic mechanisms in the ileal epithelium. Phenotype or reactivity of major effector intraepithelial CD8αβ(+) T cells were not altered in the absence of luminal iron. Interestingly, ER stress mechanisms sensitised the small intestinal epithelial cell (IEC) line Mode-K to cytotoxic function of effector T cells from TNF(ARE/WT) mice. Pyrosequencing of 16S rRNA tags of the caecal microbiota revealed that depletion of luminal iron sulfate induced significant compositional alterations, while total microbial diversity (Shannon's diversity index) and number of total operational taxonomic units were not affected.
This study showed that an iron sulfate free diet in combination with systemic iron repletion prevents the development of chronic ileitis in a murine model of Crohn's disease. Luminal iron may directly affect IEC function or generate a pathological milieu in the intestine that triggers epithelial cell stress-associated apoptosis through changes in microbial homeostasis. These results suggest that oral replacement therapy with iron sulfate may trigger inflammatory processes associated with progression of Crohn's disease-like ileitis.
Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing ...these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.
O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome. They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase ...isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment. Here, we develop a “bump–hole” chemical reporter system for studying GalNAc-T activity in vitro. Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme–substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme–substrate pairs. The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate. A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
The flat-spectrum radio quasar CTA 102 (redshift 1.037) exhibited a tremendously bright four-month-long outburst from late 2016 to early 2017. In a previous paper, we interpreted the event as the ...ablation of a gas cloud by the relativistic jet. The multiwavelength data have been reproduced very well within this model using a leptonic emission scenario. Here we expand that work by using a hadronic scenario, which gives us greater freedom with respect to the location of the emission region within the jet. This is important, since the inferred gas cloud parameters depend on the distance from the black hole. While the hadronic model faces the problem of invoking super-Eddington jet luminosities, it reproduces well the long-term trend and also days-long subflares. While the latter result in inferred cloud parameters that match those expected for clouds of the broad-line region, the long-term trend is not compatible with such an interpretation. We explore the possibilities that the cloud is from the atmosphere of a red giant star or comes from a star-forming region that passes through the jet. The latter could also explain the much longer-lasting activity phase of CTA 102 from late 2015 until early 2018.
Visualization experiments are performed to investigate the development of instability waves within the boundary layer on a slender cone under high Mach number conditions. The experimental facility is ...a reflected-shock wind tunnel, allowing both low (Mach-8 flight equivalent) and high-enthalpy conditions to be simulated. Second-mode instability waves are visualized using a high-speed schlieren set-up, with pulse bursting of the light source allowing the propagation speed of the wavepackets to be unambiguously resolved. This, in combination with wavelength information derived from the images, enables the calculation of the disturbance frequencies. At the lower-enthalpy conditions, we concentrate on the late laminar and transitional regions of the flow. General characteristics are revealed through time-resolved and ensemble-averaged spectra on both smooth and porous ceramic surfaces of the cone. Analysis of the development of individual wavepackets is then performed. It is found that the wavepacket structures evolve from a ‘rope-like’ appearance to become more interwoven as the disturbance nears breakdown. The wall-normal disturbance distributions of both the fundamental and first harmonic, which initially have local maxima at the wall and near
$y/{\it\delta}=0.7$
–0.75, exhibit an increase in signal energy close to the boundary-layer edge during this evolution. The structure angle of the disturbances also undergoes subtle changes as the wavepacket develops prior to breakdown. Experiments are also performed at high-enthalpy (
$h_{0}\approx 12~\text{MJ}~\text{kg}^{-1}$
) conditions in the laminar regime, and the visualization technique is shown to be capable of resolving wavepacket propagation speeds and frequencies at such conditions. The visualizations reveal a somewhat different wall-normal distribution to the low-enthalpy case, with the disturbance energy concentrated much more towards the wall. This is attributed to the highly cooled nature of the wall at high enthalpy.
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