2,344 research outputs found
Topological kink plasmons on magnetic-domain boundaries.
Two-dimensional topological materials bearing time reversal-breaking magnetic fields support protected one-way edge modes. Normally, these edge modes adhere to physical edges where material properties change abruptly. However, even in homogeneous materials, topology still permits a unique form of edge modes - kink modes - residing at the domain boundaries of magnetic fields within the materials. This scenario, despite being predicted in theory, has rarely been demonstrated experimentally. Here, we report our observation of topologically-protected high-frequency kink modes - kink magnetoplasmons (KMPs) - in a GaAs/AlGaAs two-dimensional electron gas (2DEG) system. These KMPs arise at a domain boundary projected from an externally-patterned magnetic field onto a uniform 2DEG. They propagate unidirectionally along the boundary, protected by a difference of gap Chern numbers ([Formula: see text]) in the two domains. They exhibit large tunability under an applied magnetic field or gate voltage, and clear signatures of nonreciprocity even under weak-coupling to evanescent photons
Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids
The development of in vitro culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation ex vivo in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland in vivo. Alternative conditions are also described that promote enrichment of basal cells organized into multiple layers surrounding a keratinous core, reminiscent of structures observed in MMTV-Wnt1 tumours. These conditions comprise a unique tool that should further understanding of normal mammary gland development, the molecular mechanism of hormone action and signalling events whose deregulation leads to breast tumourigenesis
Parameterization Effects in the analysis of AMI Sunyaev-Zel'dovich Observations
Most Sunyaev--Zel'dovich (SZ) and X-ray analyses of galaxy clusters try to
constrain the cluster total mass and/or gas mass using parameterised models and
assumptions of spherical symmetry and hydrostatic equilibrium. By numerically
exploring the probability distributions of the cluster parameters given the
simulated interferometric SZ data in the context of Bayesian methods, and
assuming a beta-model for the electron number density we investigate the
capability of this model and analysis to return the simulated cluster input
quantities via three rameterisations. In parameterisation I we assume that the
T is an input parameter. We find that parameterisation I can hardly constrain
the cluster parameters. We then investigate parameterisations II and III in
which fg(r200) replaces temperature as a main variable. In parameterisation II
we relate M_T(r200) and T assuming hydrostatic equilibrium. We find that
parameterisation II can constrain the cluster physical parameters but the
temperature estimate is biased low. In parameterisation III, the virial theorem
replaces the hydrostatic equilibrium assumption. We find that parameterisation
III results in unbiased estimates of the cluster properties. We generate a
second simulated cluster using a generalised NFW (GNFW) pressure profile and
analyse it with an entropy based model to take into account the temperature
gradient in our analysis and improve the cluster gas density distribution. This
model also constrains the cluster physical parameters and the results show a
radial decline in the gas temperature as expected. The mean cluster total mass
estimates are also within 1 sigma from the simulated cluster true values.
However, we find that for at least interferometric SZ analysis in practice at
the present time, there is no differences in the AMI visibilities between the
two models. This may of course change as the instruments improve.Comment: 19 pages, 13 tables, 24 figure
Safety and efficacy of arimoclomol for inclusion body myositis: a multicentre, randomised, double-blind, placebo-controlled trial
BACKGROUND: Inclusion body myositis is the most common progressive muscle wasting disease in people older than 50 years, with no effective drug treatment. Arimoclomol is an oral co-inducer of the cellular heat shock response that was safe and well-tolerated in a pilot study of inclusion body myositis, reduced key pathological markers of inclusion body myositis in two in-vitro models representing degenerative and inflammatory components of this disease, and improved disease pathology and muscle function in mutant valosin-containing protein mice. In the current study, we aimed to assess the safety, tolerability, and efficacy of arimoclomol in people with inclusion body myositis. METHODS: This multicentre, randomised, double-blind, placebo-controlled study enrolled adults in specialist neuromuscular centres in the USA (11 centres) and UK (one centre). Eligible participants had a diagnosis of inclusion body myositis fulfilling the European Neuromuscular Centre research diagnostic criteria 2011. Participants were randomised (1:1) to receive either oral arimoclomol 400 mg or matching placebo three times daily (1200 mg/day) for 20 months. The randomisation sequence was computer generated centrally using a permuted block algorithm with randomisation numbers masked to participants and trial staff, including those assessing outcomes. The primary endpoint was the change from baseline to month 20 in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) total score, assessed in all randomly assigned participants, except for those who were randomised in error and did not receive any study medication, and those who did not meet inclusion criteria. Safety analyses included all randomly assigned participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02753530, and is completed. FINDINGS: Between Aug 16, 2017 and May 22, 2019, 152 participants with inclusion body myositis were randomly assigned to arimoclomol (n=74) or placebo (n=78). One participant was randomised in error (to arimoclomol) but not treated, and another (assigned to placebo) did not meet inclusion criteria. 150 participants (114 [76%] male and 36 [24%] female) were included in the efficacy analyses, 73 in the arimoclomol group and 77 in the placebo group. 126 completed the trial on treatment (56 [77%] and 70 [90%], respectively) and the most common reason for treatment discontinuation was adverse events. At month 20, mean IBMFRS change from baseline was not statistically significantly different between arimoclomol and placebo (-3·26, 95% CI -4·15 to -2·36 in the arimoclomol group vs -2·26, -3·11 to -1·41 in the placebo group; mean difference -0·99 [95% CI -2·23 to 0·24]; p=0·12). Adverse events leading to discontinuation occurred in 13 (18%) of 73 participants in the arimoclomol group and four (5%) of 78 participants in the placebo group. Serious adverse events occurred in 11 (15%) participants in the arimoclomol group and 18 (23%) in the placebo group. Elevated transaminases three times or more of the upper limit of normal occurred in five (7%) participants in the arimoclomol group and one (1%) in the placebo group. Tubulointerstitial nephritis was observed in one (1%) participant in the arimoclomol group and none in the placebo group. INTERPRETATION: Arimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design. FUNDING: US Food and Drug Administration Office of Orphan Products Development and Orphazyme
Identification of the Antibacterial Compound Produced by the Marine Epiphytic Bacterium Pseudovibrio sp. D323 and Related Sponge-Associated Bacteria
Surface-associated marine bacteria often produce secondary metabolites with antagonistic activities. In this study, tropodithietic acid (TDA) was identified to be responsible for the antibacterial activity of the marine epiphytic bacterium Pseudovibrio sp. D323 and related strains. Phenol was also produced by these bacteria but was not directly related to the antibacterial activity. TDA was shown to effectively inhibit a range of marine bacteria from various phylogenetic groups. However TDA-producers themselves were resistant and are likely to possess resistance mechanism preventing autoinhibition. We propose that TDA in isolate D323 and related eukaryote-associated bacteria plays a role in defending the host organism against unwanted microbial colonisation and, possibly, bacterial pathogens
The Near Infrared Imager and Slitless Spectrograph for JWST -- V. Kernel Phase Imaging and Data Analysis
Kernel phase imaging (KPI) enables the direct detection of substellar
companions and circumstellar dust close to and below the classical (Rayleigh)
diffraction limit. We present a kernel phase analysis of JWST NIRISS full pupil
images taken during the instrument commissioning and compare the performance to
closely related NIRISS aperture masking interferometry (AMI) observations. For
this purpose, we develop and make publicly available the custom "Kpi3Pipeline"
enabling the extraction of kernel phase observables from JWST images. The
extracted observables are saved into a new and versatile kernel phase FITS file
(KPFITS) data exchange format. Furthermore, we present our new and publicly
available "fouriever" toolkit which can be used to search for companions and
derive detection limits from KPI, AMI, and long-baseline interferometry
observations while accounting for correlated uncertainties in the model fitting
process. Among the four KPI targets that were observed during NIRISS instrument
commissioning, we discover a low-contrast (~1:5) close-in (~1 )
companion candidate around CPD-66~562 and a new high-contrast (~1:170)
detection separated by ~1.5 from 2MASS~J062802.01-663738.0. The
5- companion detection limits around the other two targets reach ~6.5
mag at ~200 mas and ~7 mag at ~400 mas. Comparing these limits to those
obtained from the NIRISS AMI commissioning observations, we find that KPI and
AMI perform similar in the same amount of observing time. Due to its 5.6 times
higher throughput if compared to AMI, KPI is beneficial for observing faint
targets and superior to AMI at separations >325 mas. At very small separations
(<100 mas) and between ~250-325 mas, AMI slightly outperforms KPI which suffers
from increased photon noise from the core and the first Airy ring of the
point-spread function.Comment: 34 pages, 17 figures, accepted for publication in PAS
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