Variational description of multi-fluid hydrodynamics: Uncharged fluids

We present a formalism for Newtonian multi-fluid hydrodynamics derived from an unconstrained variational principle. This approach provides a natural way of obtaining the general equations of motion for a wide range of hydrodynamic systems containing an arbitrary number of interacting fluids and superfluids. In addition to spatial variations we use ``time shifts'' in the variational principle, which allows us to describe dissipative processes with entropy creation, such as chemical reactions, friction or the effects of external non-conservative forces. The resulting framework incorporates the generalization of the entrainment effect originally discussed in the case of the mixture of two superfluids by Andreev and Bashkin. In addition to the conservation of energy and momentum, we derive the generalized conservation laws of vorticity and helicity, and the special case of Ertel's theorem for the single perfect fluid. We explicitly discuss the application of this framework to thermally conducting fluids, superfluids, and superfluid neutron star matter. The equations governing thermally conducting fluids are found to be more general than the standard description, as the effect of entrainment usually seems to be overlooked in this context. In the case of superfluid He4 we recover the Landau--Khalatnikov equations of the two-fluid model via a translation to the ``orthodox'' framework of superfluidity, which is based on a rather awkward choice of variables. Our two-fluid model for superfluid neutron star matter allows for dissipation via mutual friction and also ``transfusion'' via beta-reactions between the neutron fluid and the proton-electron fluid.Comment: uses RevTeX 4; 20 pages. To appear in PRD. v2: removed discussion of charged fluids and coupling to electromagnetic fields, which are submitted as a separate paper for a clearer presentation v3: fixed typo in Eq.(9), updated some reference

Galaxy bulges and their massive black holes: a review

With references to both key and oft-forgotten pioneering works, this article starts by presenting a review into how we came to believe in the existence of massive black holes at the centres of galaxies. It then presents the historical development of the near-linear (black hole)-(host spheroid) mass relation, before explaining why this has recently been dramatically revised. Past disagreement over the slope of the (black hole)-(velocity dispersion) relation is also explained, and the discovery of sub-structure within the (black hole)-(velocity dispersion) diagram is discussed. As the search for the fundamental connection between massive black holes and their host galaxies continues, the competing array of additional black hole mass scaling relations for samples of predominantly inactive galaxies are presented.Comment: Invited (15 Feb. 2014) review article (submitted 16 Nov. 2014). 590 references, 9 figures, 25 pages in emulateApJ format. To appear in "Galactic Bulges", E. Laurikainen, R.F. Peletier, and D.A. Gadotti (eds.), Springer Publishin

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New NBIA subtype: Genetic, clinical, pathologic, and radiographic features of MPAN

Objective: to assess the frequency of mutations in C19orf12 in the greater neurodegeneration with brain iron accumulation (NBIA) population and further characterize the associated phenotype.Methods: samples from 161 individuals with idiopathic NBIA were screened, and C19orf12 mutations were identified in 23 subjects. Direct examinations were completed on 8 of these individuals, and medical records were reviewed on all 23. Histochemical and immunohistochemical studies were performed on brain tissue from one deceased subject.Results: a variety of mutations were detected in this cohort, in addition to the Eastern European founder mutation described previously. The characteristic clinical features of mitochondrial membrane protein-associated neurodegeneration (MPAN) across all age groups include cognitive decline progressing to dementia, prominent neuropsychiatric abnormalities, and a motor neuronopathy. A distinctive pattern of brain iron accumulation is universal. Neuropathologic studies revealed neuronal loss, widespread iron deposits, and eosinophilic spheroidal structures in the basal ganglia. Lewy neurites were present in the globus pallidus, and Lewy bodies and neurites were widespread in other areas of the corpus striatum and midbrain structures.Conclusions: MPAN is caused by mutations in C19orf12 leading to NBIA and prominent, widespread Lewy body pathology. The clinical phenotype is recognizable and distinctive, and joins pantothenate kinase-associated neurodegeneration and PLA2G6-associated neurodegeneration as one of the major forms of NBI