Indirect biomarkers of blood doping: A systematic review.

The detection of blood doping represents a current major issue in sports and an ongoing challenge for antidoping research. Initially focusing on direct detection methods to identify a banned substance or its metabolites, the antidoping effort has been progressively complemented by indirect approaches. The longitudinal and individual monitoring of specific biomarkers aims to identify nonphysiological variations that may be related to doping practices. From this perspective, the identification of markers sensitive to erythropoiesis alteration is key in the screening of blood doping. The current Athlete Biological Passport implemented since 2009 is composed of 14 variables (including two primary markers, i.e., hemoglobin concentration and OFF score) for the hematological module to be used for indirect detection of blood doping. Nevertheless, research has continually proposed and investigated new markers sensitive to an alteration of the erythropoietic cascade and specific to blood doping. If multiple early markers have been identified (at the transcriptomic level) or developed directly in a diagnostics' kit (at a proteomic level), other target variables at the end of the erythropoietic process (linked with the red blood cell functions) may strengthen the hematological module in the future. Therefore, this review aims to provide a global systematic overview of the biomarkers considered to date in the indirect investigation of blood doping

Structure and dynamics of a constitutively active neurotensin receptor

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecular dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. The loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist

Privacy Architectures: Reasoning About Data Minimisation and Integrity

Privacy by design will become a legal obligation in the European Community if the Data Protection Regulation eventually gets adopted. However, taking into account privacy requirements in the design of a system is a challenging task. We propose an approach based on the specification of privacy architectures and focus on a key aspect of privacy, data minimisation, and its tension with integrity requirements. We illustrate our formal framework through a smart metering case study.Comment: appears in STM - 10th International Workshop on Security and Trust Management 8743 (2014

A neutral hydrogen survey of polar ring galaxies IV. Parkes observations

A total of 33 polar ring galaxies and polar ring galaxy candidates were observed in the 21-cm HI line with the 64-m Parkes radio telescope. The objects, selected by their optical morphology, are all south of declination -39 degrees and in only 5 of them HI had been reported previously. HI line emission was detected towards 18 objects, though in 3 cases the detection may be confused by another galaxy in the telescope beam, and one is a marginal detection. Eight objects were detected for the first time in HI, of which 5 did not have previously known redshifts.Comment: Accepted by Astronomy and Astrophysics, 12/2/2002; new references added on 20/2/200

FACT -- The G-APD revolution in Cherenkov astronomy

Since two years, the FACT telescope is operating on the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD), equipped with solid light guides to increase the effective light collection area of each sensor. Since no sense-line is available, a special challenge is to keep the applied voltage stable although the current drawn by the G-APD depends on the flux of night-sky background photons significantly varying with ambient light conditions. Methods have been developed to keep the temperature and voltage dependent response of the G-APDs stable during operation. As a cross-check, dark count spectra with high statistics have been taken under different environmental conditions. In this presentation, the project, the developed methods and the experience from two years of operation of the first G-APD based camera in Cherenkov astronomy under changing environmental conditions will be presented.Comment: Proceedings of the Nuclear Science Symposium and Medical Imaging Conference (IEEE-NSS/MIC), 201

Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia.

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia

The Outer Disks of Early-Type Galaxies. I. Surface-Brightness Profiles of Barred Galaxies

We present a study of 66 barred, early-type (S0-Sb) disk galaxies, focused on the disk surface brightness profile outside the bar region and the nature of Freeman Type I and II profiles, their origins, and their possible relation to disk truncations. This paper discusses the data and their reduction, outlines our classification system, and presents $R$-band profiles and classifications for all galaxies in the sample. The profiles are derived from a variety of different sources, including the Sloan Digital Sky Survey (Data Release 5). For about half of the galaxies, we have profiles derived from more than one telescope; this allows us to check the stability and repeatability of our profile extraction and classification. The vast majority of the profiles are reliable down to levels of mu_R ~ 27 mag arcsec^-2; in exceptional cases, we can trace profiles down to mu_R > 28. We can typically follow disk profiles out to at least 1.5 times the traditional optical radius R_25; for some galaxies, we find light extending to ~ 3 R_25. We classify the profiles into three main groups: Type I (single-exponential), Type II (down-bending), and Type III (up-bending). The frequencies of these types are approximately 27%, 42%, and 24%, respectively, plus another 6% which are combinations of Types II and III. We further classify Type II profiles by where the break falls in relation to the bar length, and in terms of the postulated mechanisms for breaks at large radii ("classical trunction" of star formation versus the influence of the Outer Lindblad Resonance of the bar). We also classify the Type III profiles by the probable morphology of the outer light (disk or spheroid). Illustrations are given for all cases. (Abridged)Comment: 41 pages, 26 PDF figures. To appear in the Astronomical Journal. Version with full-resolution figures available at http://www.mpe.mpg.de/~erwin/research

Методы измерения фазового сдвига с промежуточным преобразованием напряжение-частота

В статті розглянуті методи вимірювання фазового зсуву з проміжним перетворенням напруга-частота. Проаналізовано переваги й недоліки методів. Проведено оцінку похибки, обумовленої неточністю формування часових інтервалів.In article methods of measurement of phase shift with preliminary transformation a voltage-frequency are considered. Their merits and demerits are analyzed. The estimation of the error caused by discrepancy of formation of time intervals is made