Co-occurrence of a novel PDGFRB variant and likely pathogenic variant in CASR in an individual with extensive intracranial calcifications and hypocalcaemia

No abstract available

HE0107-5240, A Chemically Ancient Star.I. A Detailed Abundance Analysis

We report a detailed abundance analysis for HE0107-5240, a halo giant with [Fe/H]_NLTE=-5.3. This star was discovered in the course of follow-up medium-resolution spectroscopy of extremely metal-poor candidates selected from the digitized Hamburg/ESO objective-prism survey. On the basis of high-resolution VLT/UVES spectra, we derive abundances for 8 elements (C, N, Na, Mg, Ca, Ti, Fe, and Ni), and upper limits for another 12 elements. A plane-parallel LTE model atmosphere has been specifically tailored for the chemical composition of {\he}. Scenarios for the origin of the abundance pattern observed in the star are discussed. We argue that HE0107-5240 is most likely not a post-AGB star, and that the extremely low abundances of the iron-peak, and other elements, are not due to selective dust depletion. The abundance pattern of HE0107-5240 can be explained by pre-enrichment from a zero-metallicity type-II supernova of 20-25M_Sun, plus either self-enrichment with C and N, or production of these elements in the AGB phase of a formerly more massive companion, which is now a white dwarf. However, significant radial velocity variations have not been detected within the 52 days covered by our moderate-and high-resolution spectra. Alternatively, the abundance pattern can be explained by enrichment of the gas cloud from which HE0107-5240 formed by a 25M_Sun first-generation star exploding as a subluminous SNII, as proposed by Umeda & Nomoto (2003). We discuss consequences of the existence of HE0107-5240 for low-mass star formation in extremely metal-poor environments, and for currently ongoing and future searches for the most metal-poor stars in the Galaxy.Comment: 60 pages, 16 figures. Accepted for publication in Ap

Transport Coefficients for Granular Media from Molecular Dynamics Simulations

Under many conditions, macroscopic grains flow like a fluid; kinetic theory pred icts continuum equations of motion for this granular fluid. In order to test the theory, we perform event driven molecular simulations of a two-dimensional gas of inelastic hard disks, driven by contact with a heat bath. Even for strong dissipation, high densities, and small numbers of particles, we find that continuum theory describes the system well. With a bath that heats the gas homogeneously, strong velocity correlations produce a slightly smaller energy loss due to inelastic collisions than that predicted by kinetic theory. With an inhomogeneous heat bath, thermal or velocity gradients are induced. Determination of the resulting fluxes allows calculation of the thermal conductivity and shear viscosity, which are compared to the predictions of granular kinetic theory, and which can be used in continuum modeling of granular flows. The shear viscosity is close to the prediction of kinetic theory, while the thermal conductivity can be overestimated by a factor of 2; in each case, transport is lowered with increasing inelasticity.Comment: 14 pages, 17 figures, 39 references, submitted to PRE feb 199

Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series

The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers

A spectroscopic and proper motion search of Sloan Digital Sky Survey : red subdwarfs in binary systems

Red subdwarfs in binary systems are crucial for both model calibration and spectral classification. We search for red subdwarfs in binary systems from a sample of high proper motion objects with Sloan Digital Sky Survey spectroscopy. We present here discoveries from this search, as well as highlight several additional objects of interest. We find 30 red subdwarfs in wide binary systems including: two with spectral type of esdM5.5, 6 companions to white dwarfs and 3 carbon-enhanced red subdwarfs with normal red subdwarf companions. 15 red subdwarfs in our sample are partially resolved close binary systems. With this binary sample, we estimate the low limit of the red subdwarf binary fraction of similar to 10 per cent. We find that the binary fraction goes down with decreasing masses and metallicities of red subdwarfs. A spectroscopic esdK7 subdwarf + white dwarf binary candidate is also reported. 30 new M subdwarfs have spectral type of >= M6 in our sample. We also derive relationships between spectral types and absolute magnitudes in the optical and near-infrared for M and L subdwarfs, and we present an M subdwarf sample with measured U, V, W space velocities.Peer reviewe

Symmetrical Corticobasal Syndrome Caused by a Novel c.314dup Progranulin Mutation

Corticobasal syndrome (CBS) is characterised by asymmetrical parkinsonism and cognitive impairment. The underlying pathology varies between corticobasal degeneration, progressive supranuclear palsy, Alzheimer’s disease, Creutzfeldt–Jakob disease and frontotemporal lobar degeneration sometimes in association with GRN mutations. A 61-year-old male underwent neurological examination, neuropsychological assessment, MRI, and HMPAO-SPECT at our medical centre. After his death at the age of 63, brain autopsy, genetic screening and mRNA expression analysis were performed. The patient presented with slow progressive walking disabilities, non-fluent language problems, behavioural changes and forgetfulness. His family history was negative. He had primitive reflexes, rigidity of his arms and postural instability. Later in the disease course he developed dystonia of his left leg, pathological crying, mutism and dysphagia. Neuropsychological assessment revealed prominent ideomotor and ideational apraxia, executive dysfunction, non-fluent aphasia and memory deficits. Neuroimaging showed symmetrical predominant frontoparietal atrophy and hypoperfusion. Frontotemporal lobar degeneration (FTLD)-TDP type 3 pathology was found at autopsy. GRN sequencing revealed a novel frameshift mutation c.314dup, p.Cys105fs and GRN mRNA levels showed a 50% decrease. We found a novel GRN mutation in a patient with an atypical (CBS) presentation with symmetric neuroimaging findings. GRN mutations are an important cause of CBS associated with FTLD-TDP type 3 pathology, sometimes in sporadic cases. Screening for GRN mutations should also be considered in CBS patients without a positive family history

Graphene re-knits its holes

Nano-holes, etched under an electron beam at room temperature in singlelayer graphene sheets as a result of their interaction with metalimpurities, are shown to heal spontaneously by filling up with either non-hexagon, graphene-like, or perfect hexagon 2D structures. Scanning transmission electron microscopy was employed to capture the healing process and study atom-by-atom the re-grown structure. A combination of these nano-scale etching and re-knitting processes could lead to new graphene tailoring approaches.Comment: 11 pages, 4 figure