685 research outputs found
Ab initio calculation of the neutron-proton mass difference
The existence and stability of atoms rely on the fact that neutrons are more
massive than protons. The measured mass difference is only 0.14\% of the
average of the two masses. A slightly smaller or larger value would have led to
a dramatically different universe. Here, we show that this difference results
from the competition between electromagnetic and mass isospin breaking effects.
We performed lattice quantum-chromodynamics and quantum-electrodynamics
computations with four nondegenerate Wilson fermion flavors and computed the
neutron-proton mass-splitting with an accuracy of kilo-electron volts,
which is greater than by standard deviations. We also determine the
splittings in the , , and isospin multiplets,
exceeding in some cases the precision of experimental measurements.Comment: 57 pages, 15 figures, 6 tables, revised versio
Optimal solution characterization for infinite positive semi-definite programming
We give a set-theoretic description of the set of optimal solutions to a general positive semi-definite quadratic programming problem over an affine set. We also show that the solution space is again an affine set, thus offering the opportunity to find an optimal solution by solving a corresponding operator equation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31452/1/0000373.pd
Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women
Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer
Convergence of selections with applications in optimization
We consider the problem of finding an easily implemented tie-breaking rule for a convergent set-valued algorithm, i.e., a sequence of compact, non-empty subsets of a metric space converging in the Hausdorff metric. Our tie-breaking rule is determined by nearest-point selections defined by "uniqueness" points in the space, i.e., points having a unique best approximation in the limit set of the convergent algorithm. Convergence of the algorithm is shown to be equivalent to convergence of all such nearest-point selections. Under reasonable additional hypotheses, all points in the metric space have the uniqueness property. Consequently, all points yield convergent nearest-point selections, i.e., tie-breaking rules, for a convergent algorithm.We then show how to apply these results to approximate solutions for the following types of problems: infinite systems of inequalities, semi-infinite mathematical programming, non-convex optimization, and infinite horizon optimization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29485/1/0000571.pd
Dravet syndrome as epileptic encephalopathy: Evidence from long-term course and neuropathology
Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy
An all-solid-state laser source at 671 nm for cold atom experiments with lithium
We present an all solid-state narrow line-width laser source emitting
output power at delivered in a
diffraction-limited beam. The \linebreak source is based on a
fre-quency-doubled diode-end-linebreak pumped ring laser operating on the
transition in Nd:YVO. By using
periodically-poled po-tassium titanyl phosphate (ppKTP) in an external build-up
cavity, doubling efficiencies of up to 86% are obtained. Tunability of the
source over is accomplished. We demonstrate the suitability of
this robust frequency-stabilized light source for laser cooling of lithium
atoms. Finally a simplified design based on intra-cavity doubling is described
and first results are presented
PRIMA1 mutation: A new cause of nocturnal frontal lobe epilepsy
Objective
Nocturnal frontal lobe epilepsy (NFLE) can be sporadic or autosomal dominant; some families have nicotinic acetylcholine receptor subunit mutations. We report a novel autosomal recessive phenotype in a single family and identify the causative gene.
Methods
Whole exome sequencing data was used to map the family, thereby narrowing exome search space, and then to identify the mutation.
Results
Linkage analysis using exome sequence data from two affected and two unaffected subjects showed homozygous linkage peaks on chromosomes 7, 8, 13, and 14 with maximum LOD scores between 1.5 and 1.93. Exome variant filtering under these peaks revealed that the affected siblings were homozygous for a novel splice site mutation (c.93+2T>C) in the PRIMA1 gene on chromosome 14. No additional PRIMA1 mutations were found in 300 other NFLE cases. The c.93+2T>C mutation was shown to lead to skipping of the first coding exon of the PRIMA1 mRNA using a minigene system.
Interpretation
PRIMA1 is a transmembrane protein that anchors acetylcholinesterase (AChE), an enzyme hydrolyzing acetycholine, to membrane rafts of neurons. PRiMA knockout mice have reduction of AChE and accumulation of acetylcholine at the synapse; our minigene analysis suggests that the c.93+2T>C mutation leads to knockout of PRIMA1. Mutations with gain of function effects in acetylcholine receptor subunits cause autosomal dominant NFLE. Thus, enhanced cholinergic responses are the likely cause of the severe NFLE and intellectual disability segregating in this family, representing the first recessive case to be reported and the first PRIMA1 mutation implicated in disease
Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy
First published: 16 February 2022Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.Arlene M. D’Silva, Sandra Holland, Didu Kariyawasam, Karen Herbert, Peter Barclay, Anita Cairns, Suzanna C. MacLennan, Monique M. Ryan, Hugo Sampaio, Nicholas Smith, Ian R. Woodcock, Eppie M. Yiu, Ian E. Alexander and Michelle A. Farra
Physics of Solar Prominences: I - Spectral Diagnostics and Non-LTE Modelling
This review paper outlines background information and covers recent advances
made via the analysis of spectra and images of prominence plasma and the
increased sophistication of non-LTE (ie when there is a departure from Local
Thermodynamic Equilibrium) radiative transfer models. We first describe the
spectral inversion techniques that have been used to infer the plasma
parameters important for the general properties of the prominence plasma in
both its cool core and the hotter prominence-corona transition region. We also
review studies devoted to the observation of bulk motions of the prominence
plasma and to the determination of prominence mass. However, a simple inversion
of spectroscopic data usually fails when the lines become optically thick at
certain wavelengths. Therefore, complex non-LTE models become necessary. We
thus present the basics of non-LTE radiative transfer theory and the associated
multi-level radiative transfer problems. The main results of one- and
two-dimensional models of the prominences and their fine-structures are
presented. We then discuss the energy balance in various prominence models.
Finally, we outline the outstanding observational and theoretical questions,
and the directions for future progress in our understanding of solar
prominences.Comment: 96 pages, 37 figures, Space Science Reviews. Some figures may have a
better resolution in the published version. New version reflects minor
changes brought after proof editin
System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV
We present azimuthal angle correlations of intermediate transverse momentum
(1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) =
62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is
broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and
semi-central collisions in all the systems. The broadening and peak location
are found to depend upon the number of participants in the collision, but not
on the collision energy or beam nuclei. These results are consistent with sound
or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables.
Submitted to Physical Review Letters. Plain text data tables for the points
plotted in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
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