Relativistic Positioning Systems: The Emission Coordinates

This paper introduces some general properties of the gravitational metric and the natural basis of vectors and covectors in 4-dimensional emission coordinates. Emission coordinates are a class of space-time coordinates defined and generated by 4 emitters (satellites) broadcasting their proper time by means of electromagnetic signals. They are a constitutive ingredient of the simplest conceivable relativistic positioning systems. Their study is aimed to develop a theory of these positioning systems, based on the framework and concepts of general relativity, as opposed to introducing `relativistic effects' in a classical framework. In particular, we characterize the causal character of the coordinate vectors, covectors and 2-planes, which are of an unusual type. We obtain the inequality conditions for the contravariant metric to be Lorentzian, and the non-trivial and unexpected identities satisfied by the angles formed by each pair of natural vectors. We also prove that the metric can be naturally split in such a way that there appear 2 parameters (scalar functions) dependent exclusively on the trajectory of the emitters, hence independent of the time broadcast, and 4 parameters, one for each emitter, scaling linearly with the time broadcast by the corresponding satellite, hence independent of the others.Comment: 13 pages, 3 figures. Only format changed for a new submission. Submitted to Class. Quantum Gra

Positioning systems in Minkowski space-time: from emission to inertial coordinates

The coordinate transformation between emission coordinates and inertial coordinates in Minkowski space-time is obtained for arbitrary configurations of the emitters. It appears that a positioning system always generates two different coordinate domains, namely, the front and the back emission coordinate domains. For both domains, the corresponding covariant expression of the transformation is explicitly given in terms of the emitter world-lines. This task requires the notion of orientation of an emitter configuration. The orientation is shown to be computable from the emission coordinates for the users of a `central' region of the front emission coordinate domain. Other space-time regions associated with the emission coordinates are also outlined.Comment: 20 pages; 1 figur

Kerr-Schild Symmetries

We study continuous groups of generalized Kerr-Schild transformations and the vector fields that generate them in any n-dimensional manifold with a Lorentzian metric. We prove that all these vector fields can be intrinsically characterized and that they constitute a Lie algebra if the null deformation direction is fixed. The properties of these Lie algebras are briefly analyzed and we show that they are generically finite-dimensional but that they may have infinite dimension in some relevant situations. The most general vector fields of the above type are explicitly constructed for the following cases: any two-dimensional metric, the general spherically symmetric metric and deformation direction, and the flat metric with parallel or cylindrical deformation directions.Comment: 15 pages, no figures, LaTe

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

The SITLESS project: Exercise referral schemes enhanced by self-management strategies to battle sedentary behaviour in older adults: Study protocol for a randomised controlled trial

Abstract Background Older adults are the fastest growing segment of the world‘s population. Recent evidence indicates that excessive sitting time is harmful to health, independent of meeting the recommended moderate to vigorous physical activity (PA) guidelines. The SITLESS project aims to determine whether exercise referral schemes (ERS) can be enhanced by self-management strategies (SMSs) to reduce sedentary behaviour (SB), increase PA and improve health, quality of life and function in the long term, as well as psychosocial outcomes in community-dwelling older European citizens from four countries, within a three-armed pragmatic randomised controlled trial, compared with ERS alone and also with general recommendations about PA. Methods A total of 1338 older adults will be included in this study, recruited from four European countries through different existing primary prevention pathways. Participants will be randomly allocated into an ERS of 16 weeks (32 sessions, 45–60 min per session), ERS enhanced by seven sessions of SMSs and four telephone prompts, or a control group. Outcomes will be assessed at baseline, month 4 (end of ERS intervention), month 16 (12 months post intervention) and month 22 (18 months post intervention). Primary outcomes will include measures of SB (time spent sedentary) and PA (counts per minute). Secondary outcomes will include muscle and physical function, health economics’ related outcomes, anthropometry, quality of life, social networks, anxiety and depressive symptoms, disability, fear of falling, executive function and fatigue. A process evaluation will be conducted throughout the trial. The full analysis set will follow an intention-to-treat principle and will include all randomised participants for whom a baseline assessment is conducted. The study hypothesis will be tested with mixed linear models with repeated measures, to assess changes in the main outcomes (SB and PA) over time (baseline to month 22) and between study arms. Discussion The findings of this study may help inform the design and implementation of more effective interventions to reduce SB and increase PA levels, and hence improve long-term health outcomes in the older adult population. SITLESS aims to support policy-makers in deciding how or whether ERS should be further implemented or restructured in order to increase its adherence, impact and cost-effectiveness. Trial registration ClinicalTrials.gov, NCT02629666 . Registered 19 November 2015

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access