Evolution of redback radio pulsars in globular clusters

Context. We study the evolution of close binary systems composed of a normal, intermediate mass star and a neutron star considering a chemical composition typical of that present in globular clusters (Z = 0.001 ). Aims. We look for similarities and differences with respect to solar composition donor stars, which we have extensively studied in the past. As a definite example, we perform an application on one of the redbacks located in a globular cluster. Methods. We performed a detailed grid of models in order to find systems that represent the so-called redback binary radio pulsar systems with donor star masses between 0.6 and 2.0 solar masses and orbital periods in the range 0.2 - 0.9 days. Results. We find that the evolution of these binary systems is rather similar to those corresponding to solar composition objects, allowing us to account for the occurrence of redbacks in globular clusters, as the main physical ingredient is the irradiation feedback. Redback systems are in the quasi-RLOF state, that is. almost filling their corresponding Roche lobe. During the irradiation cycle the system alternates between semi-detached and detached states. While detached the system appears as a binary millisecond pulsar, called a redback. Circumstellar material, as seen in redbacks. is left behind after the previous semi-detached phase. Conclusions. The evolution of binary radio pulsar systems considering irradiation successfully accounts for. and provides a way for. the occurrence of redback pulsars in low-metallicity environments such as globular clusters. This is the case despite possible effects of the low metal content of the donor star that could drive systems away from redback configuration.Facultad de Ciencias Astronómicas y Geofísica

Evolution of redback radio pulsars in globular clusters

Context. We study the evolution of close binary systems composed of a normal, intermediate mass star and a neutron star considering a chemical composition typical of that present in globular clusters (Z = 0.001 ). Aims. We look for similarities and differences with respect to solar composition donor stars, which we have extensively studied in the past. As a definite example, we perform an application on one of the redbacks located in a globular cluster. Methods. We performed a detailed grid of models in order to find systems that represent the so-called redback binary radio pulsar systems with donor star masses between 0.6 and 2.0 solar masses and orbital periods in the range 0.2 - 0.9 days. Results. We find that the evolution of these binary systems is rather similar to those corresponding to solar composition objects, allowing us to account for the occurrence of redbacks in globular clusters, as the main physical ingredient is the irradiation feedback. Redback systems are in the quasi-RLOF state, that is. almost filling their corresponding Roche lobe. During the irradiation cycle the system alternates between semi-detached and detached states. While detached the system appears as a binary millisecond pulsar, called a redback. Circumstellar material, as seen in redbacks. is left behind after the previous semi-detached phase. Conclusions. The evolution of binary radio pulsar systems considering irradiation successfully accounts for. and provides a way for. the occurrence of redback pulsars in low-metallicity environments such as globular clusters. This is the case despite possible effects of the low metal content of the donor star that could drive systems away from redback configuration.Facultad de Ciencias Astronómicas y Geofísica

Evolution of redback radio pulsars in globular clusters

Context. We study the evolution of close binary systems composed of a normal, intermediate mass star and a neutron star considering a chemical composition typical of that present in globular clusters (Z = 0.001 ). Aims. We look for similarities and differences with respect to solar composition donor stars, which we have extensively studied in the past. As a definite example, we perform an application on one of the redbacks located in a globular cluster. Methods. We performed a detailed grid of models in order to find systems that represent the so-called redback binary radio pulsar systems with donor star masses between 0.6 and 2.0 solar masses and orbital periods in the range 0.2 - 0.9 days. Results. We find that the evolution of these binary systems is rather similar to those corresponding to solar composition objects, allowing us to account for the occurrence of redbacks in globular clusters, as the main physical ingredient is the irradiation feedback. Redback systems are in the quasi-RLOF state, that is. almost filling their corresponding Roche lobe. During the irradiation cycle the system alternates between semi-detached and detached states. While detached the system appears as a binary millisecond pulsar, called a redback. Circumstellar material, as seen in redbacks. is left behind after the previous semi-detached phase. Conclusions. The evolution of binary radio pulsar systems considering irradiation successfully accounts for. and provides a way for. the occurrence of redback pulsars in low-metallicity environments such as globular clusters. This is the case despite possible effects of the low metal content of the donor star that could drive systems away from redback configuration.Facultad de Ciencias Astronómicas y Geofísica

Setting clinical performance specifications to develop and evaluate biomarkers for clinical use

Background: Biomarker discovery studies often claim ‘promising’ findings, motivating further studies and marketing as medical tests. Unfortunately, the patient benefits promised are often inadequately explained to guide further evaluation, and few biomarkers have translated to improved patient care. We present a practical guide for setting minimum clinical performance specifications to strengthen clinical performance study design and interpretation. Methods: We developed a step-by-step approach using test evaluation and decision-analytic frameworks and present with illustrative examples. Results: We define clinical performance specifications as a set of criteria that quantify the clinical performance a new test must attain to allow better health outcomes than current practice. We classify the proposed patient benefits of a new test into three broad groups and describe how to set minimum clinical performance at the level where the potential harm of false-positive and false-negative results does not outweigh the benefits. (1) For add-on tests proposed to improve disease outcomes by improving detection, define an acceptable trade-off for false-positive versus true-positive results; (2) for triage tests proposed to reduce unnecessary tests and treatment by ruling out disease, define an acceptable risk of false-negatives as a safety threshold; (3) for replacement tests proposed to provide other benefits, or reduce costs, without compromising accuracy, use existing tests to benchmark minimum accuracy levels. Conclusions: Researchers can follow these guidelines to focus their study objectives and to define statistical hypotheses and sample size requirements. This way, clinical performance studies will allow conclusions about whether test performance is sufficient for intended use

AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation?

OBJECTIVE: To describe the clinico-radiological phenotype of 3 patients harboring a homozygous novel AP4M1 pathogenic mutation. METHODS: The 3 patients from an inbred family who exhibited early-onset developmental delay, tetraparesis, juvenile motor function deterioration, and intellectual deficiency were investigated by magnetic brain imaging using T1-weighted, T2-weighted, T2*-weighted, fluid-attenuated inversion recovery, susceptibility weighted imaging (SWI) sequences. Whole-exome sequencing was performed on the 3 patients. RESULTS: In the 3 patients, brain imaging identified the same pattern of bilateral SWI hyposignal of the globus pallidus, concordant with iron accumulation. A novel homozygous nonsense mutation was identified in AP4M1, segregating with the disease and leading to truncation of half of the adap domain of the protein. CONCLUSIONS: Our results suggest that AP4M1 represents a new candidate gene that should be considered in the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders and highlight the intersections between hereditary spastic paraplegia and NBIA clinical presentations

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Clinical presentation and proteomic signature of patients with TANGO2 mutations

Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with a distinct clinical and biochemical phenotype of recurrent metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, and encephalopathy with cognitive decline. We report nine subjects from seven independent families, and we studied muscle histology, respiratory chain enzyme activities in skeletal muscle and proteomic signature of fibroblasts. All nine subjects carried autosomal recessive TANGO2 mutations. Two carried the reported deletion of exons 3 to 9, one homozygous, one heterozygous with a 22q11.21 microdeletion inherited in trans. The other subjects carried three novel homozygous (c.262C&gt;T/p.Arg88*; c.220A&gt;C/p.Thr74Pro; c.380+1G&gt;A), and two further novel heterozygous (c.6_9del/p.Phe6del); c.11-13delTCT/p.Phe5del mutations. Immunoblot analysis detected a significant decrease of TANGO2 protein. Muscle histology showed mild variation of fiber diameter, no ragged-red/cytochrome c oxidase-negative fibers and a defect of multiple respiratory chain enzymes and coenzyme Q10 (CoQ10 ) in two cases, suggesting a possible secondary defect of oxidative phosphorylation. Proteomic analysis in fibroblasts revealed significant changes in components of the mitochondrial fatty acid oxidation, plasma membrane, endoplasmic reticulum-Golgi network and secretory pathways. Clinical presentation of TANGO2 mutations is homogeneous and clinically recognizable. The hemizygous mutations in two patients suggest that some mutations leading to allele loss are difficult to detect. A combined defect of the respiratory chain enzymes and CoQ10 with altered levels of several membrane proteins provides molecular insights into the underlying pathophysiology and may guide rational new therapeutic interventions.</p