102 research outputs found
Deceleration and trapping of heavy diatomic molecules using a ring-decelerator
We present an analysis of the deceleration and trapping of heavy diatomic
molecules in low-field seeking states by a moving electric potential. This
moving potential is created by a 'ring-decelerator', which consists of a series
of ring-shaped electrodes to which oscillating high voltages are applied.
Particle trajectory simulations have been used to analyze the deceleration and
trapping efficiency for a group of molecules that is of special interest for
precision measurements of fundamental discrete symmetries. For the typical case
of the SrF molecule in the (N,M) = (2, 0) state, the ring-decelerator is shown
to outperform traditional and alternate-gradient Stark decelerators by at least
an order of magnitude. If further cooled by a stage of laser cooling, the
decelerated molecules allow for a sensitivity gain in a parity violation
measurement, compared to a cryogenic molecular beam experiment, of almost two
orders of magnitude
Deleting titin's C-terminal PEVK exons increases passive stiffness, alters splicing, and induces cross-sectional and longitudinal hypertrophy in skeletal muscle
The Proline, Glutamate, Valine and Lysine-rich (PEVK) region of titin constitutes an entropic spring that provides passive tension to striated muscle. To study the functional and structural repercussions of a small reduction in the size of the PEVK region, we investigated skeletal muscles of a mouse with the constitutively expressed C-terminal PEVK exons 219–225 deleted, the Ttn(Δ219–225) model (MGI: Ttn(TM 2.1Mgot)). Based on this deletion, passive tension in skeletal muscle was predicted to be increased by ∼17% (sarcomere length 3.0 μm). In contrast, measured passive tension (sarcomere length 3.0 μm) in both soleus and EDL muscles was increased 53 ± 11% and 62 ± 4%, respectively. This unexpected increase was due to changes in titin, not to alterations in the extracellular matrix, and is likely caused by co-expression of two titin isoforms in Ttn(Δ219–225) muscles: a larger isoform that represents the Ttn(Δ219–225) N2A titin and a smaller isoform, referred to as N2A2. N2A2 represents a splicing adaption with reduced expression of spring element exons, as determined by titin exon microarray analysis. Maximal tetanic tension was increased in Ttn(Δ219–225) soleus muscle (WT 240 ± 9; Ttn(Δ219–225) 276 ± 17 mN/mm2), but was reduced in EDL muscle (WT 315 ± 9; Ttn(Δ219–225) 280 ± 14 mN/mm2). The changes in active tension coincided with a switch toward slow fiber types and, unexpectedly, faster kinetics of tension generation and relaxation. Functional overload (FO; ablation) and hindlimb suspension (HS; unloading) experiments were also conducted. Ttn(Δ219–225) mice showed increases in both longitudinal hypertrophy (increased number of sarcomeres in series) and cross-sectional hypertrophy (increased number of sarcomeres in parallel) in response to FO and attenuated cross-sectional atrophy in response to HS. In summary, slow- and fast-twitch muscles in a mouse model devoid of titin's PEVK exons 219–225 have high passive tension, due in part to alterations elsewhere in splicing of titin’s spring region, increased kinetics of tension generation and relaxation, and altered trophic responses to both functional overload and unloading. This implicates titin’s C-terminal PEVK region in regulating passive and active muscle mechanics and muscle plasticity
Inherent Inhomogeneities in Tunneling Spectra of BSCCO Crystals in the Superconducting State
Scanning Tunneling Spectroscopy on cleaved BSCCO(2212) single crystals reveal
inhomogeneities on length-scales of 30 . While most of the surface
yields spectra consistent with a d-wave superconductor, small regions show a
doubly gapped structure with both gaps lacking coherence peaks and the larger
gap having a size typical of the respective pseudo-gap for the same sample.Comment: 4 pages, 4 figure
Population redistribution in optically trapped polar molecules
We investigate the rovibrational population redistribution of polar molecules
in the electronic ground state induced by spontaneous emission and blackbody
radiation. As a model system we use optically trapped LiCs molecules formed by
photoassociation in an ultracold two-species gas. The population dynamics of
vibrational and rotational states is modeled using an ab-initio electric dipole
moment function and experimental potential energy curves. Comparison with the
evolution of the v"=3 electronic ground state yields good qualitative
agreement. The analysis provides important input to assess applications of
ultracold LiCs molecules in quantum simulation and ultracold chemistry.Comment: 6 pages, 5 figures, EPJD Topical issue on Cold Quantum Matter -
Achievements and Prospect
Slowing polar molecules using a wire Stark decelerator
We have designed and implemented a new Stark decelerator based on wire
electrodes, which is suitable for ultrahigh vacuum applications. The 100
deceleration stages are fashioned out of 0.6 mm diameter tantalum and the
array's total length is 110 mm, approximately 10 times smaller than a
conventional Stark decelerator with the same number of electrode pairs. Using
the wire decelerator, we have removed more than 90% of the kinetic energy from
metastable CO molecules in a beam.Comment: updated version, added journal referenc
Strong-correlation effects in Born effective charges
Large values of Born effective charges are generally considered as reliable
indicators of the genuine tendency of an insulator towards ferroelectric
instability. However, these quantities can be very much influenced by strong
electron correlation and metallic behavior, which are not exclusive properties
of ferroelectric materials. In this paper we compare the Born effective charges
of some prototypical ferroelectrics with those of magnetic, non-ferroelectric
compounds using a novel, self-interaction free methodology that improves on the
local-density approximation description of the electronic properties. We show
that the inclusion of strong-correlation effects systermatically reduces the
size of the Born effective charges and the electron localization lengths.
Furthermore we give an interpretation of the Born effective charges in terms of
band energy structure and orbital occupations which can be used as a guideline
to rationalize their values in the general case.Comment: 10 pages, 4 postscript figure
Treatment outcomes of patients with atopic dermatitis (AD) treated with dupilumab through the early access to medicines scheme (EAMS) in the UK
BACKGROUND
Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017.
OBJECTIVES
The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS.
METHODS
A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI).
RESULTS
Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had
received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard
deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD
severity scores showed statistically significant improvement at week 16+4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either ‘better’ (19%) or ‘much better’ (65%).
CONCLUSIONS
Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials
Low Complexity Regularization of Linear Inverse Problems
Inverse problems and regularization theory is a central theme in contemporary
signal processing, where the goal is to reconstruct an unknown signal from
partial indirect, and possibly noisy, measurements of it. A now standard method
for recovering the unknown signal is to solve a convex optimization problem
that enforces some prior knowledge about its structure. This has proved
efficient in many problems routinely encountered in imaging sciences,
statistics and machine learning. This chapter delivers a review of recent
advances in the field where the regularization prior promotes solutions
conforming to some notion of simplicity/low-complexity. These priors encompass
as popular examples sparsity and group sparsity (to capture the compressibility
of natural signals and images), total variation and analysis sparsity (to
promote piecewise regularity), and low-rank (as natural extension of sparsity
to matrix-valued data). Our aim is to provide a unified treatment of all these
regularizations under a single umbrella, namely the theory of partial
smoothness. This framework is very general and accommodates all low-complexity
regularizers just mentioned, as well as many others. Partial smoothness turns
out to be the canonical way to encode low-dimensional models that can be linear
spaces or more general smooth manifolds. This review is intended to serve as a
one stop shop toward the understanding of the theoretical properties of the
so-regularized solutions. It covers a large spectrum including: (i) recovery
guarantees and stability to noise, both in terms of -stability and
model (manifold) identification; (ii) sensitivity analysis to perturbations of
the parameters involved (in particular the observations), with applications to
unbiased risk estimation ; (iii) convergence properties of the forward-backward
proximal splitting scheme, that is particularly well suited to solve the
corresponding large-scale regularized optimization problem
Analysis of shared heritability in common disorders of the brain
Paroxysmal Cerebral Disorder
Gas sampling efficiencies and aerodynamic characteristics of a laboratory wind tunnel for odour measurement
The rate of odour emission depends on meteorological factors, such as wind speed, humidity and temperature,
but no wind tunnels control these factors adequately. A novel laboratory wind tunnel was developed that can control airflow rate. The gas recovery efficiency of the tunnel was evaluated and the aerodynamic characteristics were then examined to further assess its performance. Gas recovery efficiencies ranged from 62 to 107% with an average of 81%. The optimal performance of the tunnel (gas recovery efficiency of 89%) occurred at an airflow rate and CO supply rate of 1.68m3 min-1 and 10.0 l min-1, respectively. The vertical and cross-sectional wind speed profiles exhibited a substantial degree of non-uniformity. The airflow was turbulent, although Reynolds numbers were low indicating it to be close to laminar. The non-uniform wind
speed profiles and CO concentration profiles illustrate the difficulty in obtaining representative samples from which to calculate emission rates. Further work is required to improve aerodynamic characteristics and hence performance of the tunnel
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