43 research outputs found
Cosmic rays and molecular clouds
This paper deals with the cosmic-ray penetration into molecular clouds and
with the related gamma--ray emission. High energy cosmic rays interact with the
dense gas and produce neutral pions which in turn decay into two gamma rays.
This makes molecular clouds potential sources of gamma rays, especially if they
are located in the vicinity of a powerful accelerator that injects cosmic rays
in the interstellar medium. The amplitude and duration in time of the
cosmic--ray overdensity around a given source depend on how quickly cosmic rays
diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray
observations of molecular clouds can be used both to locate the sources of
cosmic rays and to constrain the properties of cosmic-ray diffusion in the
Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics
2012, 27 pages, 10 figure
Rare disruptive variants in the DISC1 Interactome and Regulome : association with cognitive ability and schizophrenia
Schizophrenia (SCZ), bipolar disorder (BD) and recurrent major depressive disorder (rMDD) are common psychiatric illnesses. All have been associated with lower cognitive ability, and show evidence of genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism. Disrupted in schizophrenia 1 (DISC1) protein directly interacts with a large set of proteins (DISC1 Interactome) that are involved in brain development and signaling. Modulation of DISC1 expression alters the expression of a circumscribed set of genes (DISC1 Regulome) that are also implicated in brain biology and disorder. Here we report targeted sequencing of 59 DISC1 Interactome genes and 154 Regulome genes in 654 psychiatric patients and 889 cognitively-phenotyped control subjects, on whom we previously reported evidence for trait association from complete sequencing of the DISC1 locus. Burden analyses of rare and singleton variants predicted to be damaging were performed for psychiatric disorders, cognitive variables and personality traits. The DISC1 Interactome and Regulome showed differential association across the phenotypes tested. After family-wise error correction across all traits (FWERacross), an increased burden of singleton disruptive variants in the Regulome was associated with SCZ (FWERacross P=0.0339). The burden of singleton disruptive variants in the DISC1 Interactome was associated with low cognitive ability at age 11 (FWERacross P=0.0043). These results identify altered regulation of schizophrenia candidate genes by DISC1 and its core Interactome as an alternate pathway for schizophrenia risk, consistent with the emerging effects of rare copy number variants associated with intellectual disability.Peer reviewe
Supernova remnants: the X-ray perspective
Supernova remnants are beautiful astronomical objects that are also of high
scientific interest, because they provide insights into supernova explosion
mechanisms, and because they are the likely sources of Galactic cosmic rays.
X-ray observations are an important means to study these objects.And in
particular the advances made in X-ray imaging spectroscopy over the last two
decades has greatly increased our knowledge about supernova remnants. It has
made it possible to map the products of fresh nucleosynthesis, and resulted in
the identification of regions near shock fronts that emit X-ray synchrotron
radiation.
In this text all the relevant aspects of X-ray emission from supernova
remnants are reviewed and put into the context of supernova explosion
properties and the physics and evolution of supernova remnants. The first half
of this review has a more tutorial style and discusses the basics of supernova
remnant physics and thermal and non-thermal X-ray emission. The second half
offers a review of the recent advances.The topics addressed there are core
collapse and thermonuclear supernova remnants, SN 1987A, mature supernova
remnants, mixed-morphology remnants, including a discussion of the recent
finding of overionization in some of them, and finally X-ray synchrotron
radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2
column-layout. 78 pages, 42 figures. This replaced version has some minor
language edits and several references have been correcte
Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast:a cross-sectional study of women with benign breast disease
BACKGROUND: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. METHODS: Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area (âTDLU countâ), median TDLU diameter (âTDLU spanâ), and number of acini per TDLU (âacini countâ). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. RESULTS: Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trendâ=â0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. CONCLUSIONS: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0678-4) contains supplementary material, which is available to authorized users
Personalized early detection and prevention of breast cancer: ENVISION consensus statement
Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectivenessâimplementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas