Lund University

About: Lund University is a education organization based out in Lund, Sweden. It is known for research contribution in the topics: Population & Cancer. The organization has 42345 authors who have published 124676 publications receiving 5016438 citations. The organization is also known as: Lunds Universitet & University of Lund.

The mass distribution and gravitational potential of the Milky Way

Abstract: We present mass models of the Milky Way created to fit observational constraints and to be consistent with expectations from theoretical modelling. The method used to create these models is that demonstrated in our previous study, and we improve on those models by adding gas discs to the potential, considering the effects of allowing the inner slope of the halo density profile to vary, and including new observations of maser sources in the Milky Way amongst the new constraints. We provide a best-fitting model, as well as estimates of the properties of the Milky Way. Under the assumptions in our main model, we find that the Sun is R0 = 8.20 ± 0.09 kpc from the Galactic Centre, with the circular speed at the Sun being v0 = 232.8 ± 3.0 kms-1; and that the Galaxy has a total stellar mass of (54.3 ± 5.7) × 109 M⊙, a total virial mass of (1.30 ± 0.30) × 1012M⊙ and a local dark-matter density of 0.40 ± 0.04 GeV cm-3, where the quoted uncertainties are statistical. These values are sensitive to our choice of priors and constraints. We investigate systematic uncertainties, which in some cases may be larger. For example, if we weaken our prior on R0, we find it to be 7.97 ± 0.15 kpc and that v0 = 226.8 ± 4.2 kms-1.We find that most of these properties, including the local dark-matter density, are remarkably insensitive to the assumed power-law density slope at the centre of the dark-matter halo. We find that it is unlikely that the local standard of rest differs significantly from that found under assumptions of axisymmetry. We have made code to compute the force from our potential, and to integrate orbits within it, publicly available. (Less)

HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures

Abstract: Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.

Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse

Abstract: During early mouse development the homeobox gene Hesx1 is expressed in prospective forebrain tissue, but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Mice lacking Hesx1 exhibit variable anterior CNS defects and pituitary dysplasia. Mutants have a reduced prosencephalon, anopthalmia or micropthalmia, defective olfactory development and bifurcations in Rathke's pouch. Neonates exhibit abnormalities in the corpus callosum, the anterior and hippocampal commissures, and the septum pellucidum. A comparable and equally variable phenotype in humans is septo-optic dysplasia (SOD). We have cloned human HESX1 and screened for mutations in affected individuals. Two siblings with SOD were homozygous for an Arg53Cys missense mutation within the HESX1 homeodomain which destroyed its ability to bind target DNA. These data suggest an important role for Hesx1/HESX1 in forebrain, midline and pituitary development in mouse and human.