The Peculiar Type Ia Supernova 2005hk

We present a preliminary analysis of an extensive set of optical observations of the Type Ia SN 2005hk. We show that the evolution of SN 2005hk closely follows that of the peculiar SN 2002cx. SN 2005hk is more luminous than SN 2002cx, while still under-luminous compared to normal Type Ia supernovae. The spectrum at 9 days before maximum is dominated by conspicuous Fe III and Ni III lines, and the Si II 6355 line is also clearly visible. All these features have low velocity (~6000 km/s). The near maximum spectra show lines of Si II, S II, Fe II, Fe III, as well as other intermediate mass and iron group elements. Analysis with the code for synthetic spectra SYNOW indicates that all these spectral lines have similar velocities.Comment: 6 pages, 3 figures, submitted to the proceedings of the conference``The Multicoloured Landscape of Compact Objects and their Explosive Origins'', 2006 June 11--24, Cefalu, Sicily, to be published by AI

An Unusual Stellar Death on Christmas Day

Long Gamma-Ray Bursts (GRBs) are the most dramatic examples of massive stellar deaths, usually associated with supernovae. They release ultra-relativistic jets producing non-thermal emission through synchrotron radiation as they interact with the surrounding medium. Here we report observations of the peculiar GRB 101225A (the "Christmas burst"). Its gamma-ray emission was exceptionally long and followed by a bright X-ray transient with a hot thermal component and an unusual optical couuterpart. During the first 10 days, the optical emission evolved as an expanding, cooling blackbody after which an additional component, consistent with a faint supernova, emerged. We determine its distance to 1.6 Gpc by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a helium star-neutron star merger that underwent a common envelope phase expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which gets thermalized by interacting with the dense, previously ejected material and thus creating the observed black-body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star io the Galax

The Current Status and Work of Three Rs Centres and Platforms in Europe*

The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes has given a major push to the formation of Three Rs initiatives in the form of centres and platforms. These centres and platforms are dedicated to the so-called Three Rs, which are the Replacement, Reduction and Refinement of animal use in experiments. ATLA's 50th Anniversary year has seen the publication of two articles on European Three Rs centres and platforms. The first of these was about the progressive rise in their numbers and about their founding history; this second part focuses on their current status and activities. This article takes a closer look at their financial and organisational structures, describes their Three Rs focus and core activities (dissemination, education, implementation, scientific quality/translatability, ethics), and presents their areas of responsibility and projects in detail. This overview of the work and diverse structures of the Three Rs centres and platforms is not only intended to bring them closer to the reader, but also to provide role models and show examples of how such Three Rs centres and platforms could be made sustainable. The Three Rs centres and platforms are very important focal points and play an immense role as facilitators of Directive 2010/63/EU 'on the ground' in their respective countries. They are also invaluable for the wide dissemination of information and for promoting the implementation of the Three Rs in general

The Rise of Three Rs Centres and Platforms in Europe*

Public awareness and discussion about animal experiments and replacement methods has greatly increased in recent years. The term 'the Three Rs', which stands for the Replacement, Reduction and Refinement of animal experiments, is inseparably linked in this context. A common goal within the Three Rs scientific community is to develop predictive non-animal models and to better integrate all available data from in vitro, in silico and omics technologies into regulatory decision-making processes regarding, for example, the toxicity of chemicals, drugs or food ingredients. In addition, it is a general concern to implement (human) non-animal methods in basic research. Toward these efforts, there has been an ever-increasing number of Three Rs centres and platforms established over recent years - not only to develop novel methods, but also to disseminate knowledge and help to implement the Three Rs principles in policies and education. The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes gave a strong impetus to the creation of Three Rs initiatives, in the form of centres and platforms. As the first of a series of papers, this article gives an overview of the European Three Rs centres and platforms, and their historical development. The subsequent articles, to be published over the course of ATLA's 50th Anniversary year, will summarise the current focus and tasks as well as the future and the plans of the Three Rs centres and platforms. The Three Rs centres and platforms are very important points of contact and play an immense role in their respective countries as 'on the ground' facilitators of Directive 2010/63/EU. They are also invaluable for the widespread dissemination of information and for promoting implementation of the Three Rs in general

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITEseq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multiomic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis