208 research outputs found
Anomaly Cancelation in Field Theory and F-theory on a Circle
We study the manifestation of local gauge anomalies of four- and
six-dimensional field theories in the lower-dimensional Kaluza-Klein theory
obtained after circle compactification. We identify a convenient set of
transformations acting on the whole tower of massless and massive states and
investigate their action on the low-energy effective theories in the Coulomb
branch. The maps employ higher-dimensional large gauge transformations and
precisely yield the anomaly cancelation conditions when acting on the one-loop
induced Chern-Simons terms in the three- and five-dimensional effective theory.
The arising symmetries are argued to play a key role in the study of the
M-theory to F-theory limit on Calabi-Yau manifolds. For example, using the fact
that all fully resolved F-theory geometries inducing multiple Abelian gauge
groups or non-Abelian groups admit a certain set of symmetries, we are able to
generally show the cancelation of pure Abelian or pure non-Abelian anomalies in
these models.Comment: 48 pages, 2 figures; v2: typos corrected, comments on circle fluxes
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P.025 Efficacy and safety results of the avalglucosidase alfa phase 3 COMET trial in participants with late-onset Pompe disease (LOPD)
Background: Phase 3 COMET trial (NCT02782741)
compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in
treatment-naïve LOPD. Methods: Primary objective:
determine avalglucosidase alfa effect on respiratory muscle function.
Secondary/other objectives include: avalglucosidase alfa effect on
functional endurance, inspiratory/expiratory muscle strength, lower/upper
extremity muscle strength, motor function, health-related quality of life,
safety. Results: At Week 49, change (LSmean±SE) from
baseline in upright forced vital capacity %predicted was greater with
avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa
(0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving
statistical non-inferiority (p=0.0074), was met. Superiority testing was
borderline significant (p=0.0626). Week 49 change from baseline in 6-minute
walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m)
versus alglucosidase alfa (2.19±10.40m). Positive results for
avalglucosidase alfa were seen for all secondary/other efficacy endpoints.
Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase
alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five
participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs
occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated
participants. IgG antidrug antibody responses were similar in both. High
titers and neutralizing antibodies were more common for alglucosidase alfa.
Conclusions: Results demonstrate improvements in
clinically meaningful outcome measures and a more favorable safety profile
with avalglucosidase alfa versus alglucosidase alfa.
Funding: Sanofi Genzym
Learning from Conect4children: A Collaborative Approach towards Standardization of Disease-Specific Paediatric Research Data
The conect4children (c4c) initiative was established to facilitate the development of new drugs and other therapies for paediatric patients. It is widely recognized that there are not enough medicines tested in all relevant ages of the paediatric population. To overcome this, it is imperative that clinical data from different sources are interoperable and can be pooled for larger post-hoc studies. c4c has collaborated with the Clinical Data Interchange Standards Consortium (CDISC) to develop the cross-cutting data resources that build on existing CDISC standards, in an effort to standardize paediatric data. The natural next step was an extension to disease-specific data items. c4c brought together several existing initiatives and resources relevant to disease-specific data and to analyse their use for standardizing disease-specific data in clinical trials. Several case studies that combined disease-specific data from multiple trials have demonstrated the need for disease-specific data standardization. We identified three relevant initiatives. These include European Reference Networks, European Joint Programme on Rare Diseases, and Pistoia Alliance. Other resources reviewed were: National Cancer Institute Enterprise Vocabulary Services, CDISC standards, pharmaceutical company-specific data dictionaries, Human Phenotype Ontology, Phenopackets, Unified Registry for Inherited Metabolic Disorders, Orphacodes, Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP) and Observational Medical Outcomes Partnership. The collaborative partners associated with these resources were also reviewed briefly. A plan of action focussed on collaboration was generated for standardizing disease-specific paediatric clinical trial data. A paediatric data standards multistakeholder and multi-project user group was established to guide the remaining actions– FAIRification of metadata, a Phenopackets pilot with RDCA-DAP, applying Orphacodes to case report forms of clinical trials, introducing CDISC standards into European Reference Networks, testing of the CDISC Pediatric User Guide using data from the mentioned resources and organization of further workshops and educational materials
Cross-translational studies in human and Drosophila identify markers of sleep loss
Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss
Sleep and immune function
Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations
Knowing the enemy: ant behavior and control in a pediatric hospital of Buenos Aires
Ant control is difficult in systems even where a variety of control strategies and compounds are allowed; in sensitive places such as hospitals, where there are often restrictions on the methods and toxicants to be applied, the challenge is even greater. Here we report the methods and results of how we faced this challenge of controlling ants in a pediatric hospital using baits. Our strategy was based on identifying the species present and analyzing their behavior. On the one hand, we evaluated outdoors in the green areas of the hospital, the relative abundance of ant genera, their food preferences and the behavioral dominances. On the other hand, control treatments were performed using separately two boron compounds added to sucrose solution which was not highly concentrated to avoid constrains due to the viscosity. Most of the species in the food preference test accepted sugary food; only one species was recorded to visit it less than the protein foods. This result was consistent with the efficacy of control treatments by sugary baits within the rooms. For species that showed good acceptance of sugar solutions in the preference test outdoors, sugar bait control indoors was 100& effective. Conversely, for the only species that foraged significantly less on sugar food, the bait treatment was ineffective. This work reveals the importance of considering the behavior and feeding preferences of the species to be controlled by toxic baits.Fil: Josens, Roxana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Sola, Francisco Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Marchisio, Nahuel Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Di Renzo, María Agostina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental. Laboratorio del Grupo de Estudio de Insectos Sociales; ArgentinaFil: Giacometti, Alina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin
A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors
IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole.
The main goal of IceCube is the detection of astrophysical neutrinos and the
identification of their sources. High-energy muon neutrinos are observed via
the secondary muons produced in charge current interactions with nuclei in the
ice. Currently, the best performing muon track directional reconstruction is
based on a maximum likelihood method using the arrival time distribution of
Cherenkov photons registered by the experiment's photomultipliers. A known
systematic shortcoming of the prevailing method is to assume a continuous
energy loss along the muon track. However at energies TeV the light yield
from muons is dominated by stochastic showers. This paper discusses a
generalized ansatz where the expected arrival time distribution is parametrized
by a stochastic muon energy loss pattern. This more realistic parametrization
of the loss profile leads to an improvement of the muon angular resolution of
up to for through-going tracks and up to a factor 2 for starting tracks
over existing algorithms. Additionally, the procedure to estimate the
directional reconstruction uncertainty has been improved to be more robust
against numerical errors
A search for time-dependent astrophysical neutrino emission with IceCube data from 2012 to 2017
High-energy neutrinos are unique messengers of the high-energy universe,
tracing the processes of cosmic-ray acceleration. This paper presents analyses
focusing on time-dependent neutrino point-source searches. A scan of the whole
sky, making no prior assumption about source candidates, is performed, looking
for a space and time clustering of high-energy neutrinos in data collected by
the IceCube Neutrino Observatory between 2012 and 2017. No statistically
significant evidence for a time-dependent neutrino signal is found with this
search during this period since all results are consistent with the background
expectation. Within this study period, the blazar 3C 279, showed strong
variability, inducing a very prominent gamma-ray flare observed in 2015 June.
This event motivated a dedicated study of the blazar, which consists of
searching for a time-dependent neutrino signal correlated with the gamma-ray
emission. No evidence for a time-dependent signal is found. Hence, an upper
limit on the neutrino fluence is derived, allowing us to constrain a hadronic
emission model
LeptonInjector and LeptonWeighter: A neutrino event generator and weighter for neutrino observatories
We present a high-energy neutrino event generator, called LeptonInjector,
alongside an event weighter, called LeptonWeighter. Both are designed for
large-volume Cherenkov neutrino telescopes such as IceCube. The neutrino event
generator allows for quick and flexible simulation of neutrino events within
and around the detector volume, and implements the leading Standard Model
neutrino interaction processes relevant for neutrino observatories:
neutrino-nucleon deep-inelastic scattering and neutrino-electron annihilation.
In this paper, we discuss the event generation algorithm, the weighting
algorithm, and the main functions of the publicly available code, with
examples.Comment: 28 pages, 10 figures, 3 table
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