Size effect of large scale timber columns

The very large glued laminated timber columns that are needed for tall timber buildings are too large to be physically tested in most facilities. To safely design these columns, it is necessary to identify and extrapolate behaviour from the physical testing of smaller specimens. Compression testing of 27 glue-laminated timber columns showed a reduction in strength with increased member size. This phenomenon is known as a size effect. The laminated timber exhibited a compressive strength much higher than the characteristic strength that it was graded it. Comparisons between columns of different lengths and widths, suggests that the homogenisation of laminated timber may mitigate the size effect. An extrapolation of the size effect from the column sizes tested, to an ultra-large column for a timber skyscraper, indicated that the magnitude of the effect could be large enough to reduce the compressive strength of the glulam to below its characteristic strength

Geochemical mapping of the Mariana arc-basin system: Implications for the nature and distribution of subduction components

A new ICP-MS database for glasses from the Mariana Trough, together with published and new ICP-MS data from the Mariana arc, provides the basis for geochemical mapping of the Mariana arc-basin system. The geochemical maps presented here are based on the graphic representation of spatial variations in geochemical proxies for the principal mantle and subduction components. The focus is on three elements with high and similar partition coefficients but different behavior in subduction systems, namely, Ba, Th, and Nb. Two elements with different partition coefficients, Ta and Yb, are used as normalizing factors. Ratio maps (Ta/Yb, Nb/Ta, Th/Ta, Ba/Ta, Ba/Th) provide the simplest petrogenetic insights, subduction zone addition maps based on deviations from a MORB array provide more quantitative insights, and component maps represent an attempt to isolate the different subduction components. The maps shown here indicate the presence of a variably depleted asthenosphere and three added components: a Nb-Th-Ba component, a Th-Ba deep-subduction component, and a Ba-only shallow-subduction component. The asthenosphere entering the system is enriched relative to N-MORB and appears to be focused at three sites within the Mariana Trough. The Nb-Th-Ba component is present mainly in the north of the arc (the Northern Seamount province and northern Central Island Province), the northern edge of the Mariana Trough, and two locations within the Southern Seamount Province. It has a distinctively high Nb/Ta ratio and a moderate enrichment in Th and Ba relative to Nb. Its composition and distribution indicate that it may not be part of the present subduction system but instead originates in mantle lithosphere previously enriched above the subduction zone by addition of small-degree, subduction-modified mantle melts. The Th-Ba component is present throughout the arc and, in minor amounts, in parts of the back-arc basin. The Ba-only component is mainly present in the central part of the arc and at the edges of the back-arc basin. Overall, the geochemical maps provide a new perspective on the geochemical processes that accompany the evolution of an arc basin system from prerifting lithospheric enrichment, through arc-rifting to arc volcanism and back-arc spreadin

First Results from the Swarms Survey. SDSS 1257+5428: A Nearby, Massive White Dwarf Binary with a Likely Neutron Star or Black Hole Companion

We present the first results from SWARMS (Sloan White dwArf Radial velocity data Mining Survey), an ongoing project to identify compact white dwarf (WD) binaries in the spectroscopic catalog of the Sloan Digital Sky Survey. The first object identified by SWARMS, SDSS 1257+5428, is a single-lined spectroscopic binary in a circular orbit with a period of 4.56 hr and a semiamplitude of 322.7+-6.3 km/s. From the spectrum and photometry, we estimate a WD mass of 0.92(+0.28,-0.32) Msun. Together with the orbital parameters of the binary, this implies that the unseen companion must be more massive than 1.62(+0.20,-0.25) Msun, and is in all likelihood either a neutron star or a black hole. At an estimated distance of 48(+10,-19) pc, this would be the closest known stellar remnant of a supernova explosion.Comment: 8 pages, 8 figures, ApJ in pres

Hyper-Accreting Black Holes and Gamma-Ray Bursts

A variety of current models for gamma-ray bursts (GRBs) suggest a common engine - a black hole of several solar masses accreting matter from a disk at a rate 0.01 to 10 solar masses per second. Using a numerical model for relativistic disk accretion, we have studied steady-state accretion at these high rates. Inside a radius ~ 10**8 cm, for accretion rates greater than about 0.01 solar masses per second, a global state of balanced power comes to exist between neutrino losses, chiefly pair capture on nucleons, and dissipation. Energy emitted in neutrinos is less, and in the case of low accretion rates, very much less, than the maximum efficiency factor for black hole accretion (0.057 for no rotation; 0.42 for extreme Kerr rotation) times Mdot c**2. The efficiency for producing a pair fireball along the rotational axis by neutrino annihilation is calculated and found to be highly variable and very sensitive to the accretion rate. For some of the higher accretion rates studied, it can be several per cent or more; for accretion rates less than 0.05 solar masses per second, it is essentially zero. The efficiency of the Blandford-Znajek mechanism in extracting rotational energy from the black hole is also estimated. In light of these results, the viability of various gamma-ray burst models is discussed and the sensitivity of the results to disk viscosity, black hole rotation rate, and black hole mass explored. A diverse range of GRB energies seems unavoidable and neutrino annihilation in hyper-accreting black hole systems can explain bursts up to 10**52 erg. Larger energies may be inferred for beaming systems.Comment: 46 pages, includes 9 figures, LaTeX (uses aaspp4.sty), accepted by The Astrophysical Journal. Additional solutions in Tables and Figs. 4 and 5, minor revisions to text, references adde

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline

Individuals with Down Syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological ageing. This includes brain atrophy, β-amyloid deposition, cognitive decline and Alzheimer’s Disease; factors indicative of brain ageing. Here we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [11C]-PiB positron emission tomography (PET) scans to index levels of cerebral β-amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants’ was +2.49 years, significantly greater than controls (p<0.001). The variability in brain-PAD was associated with the presence and the magnitude of PIB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain ageing, and that age-related alterations in brain structure are associated with individual differences in the rate of β-amyloid deposition and cognitive impairment

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

The pattern of amyloid accumulation in the brains of adults with Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. METHODS: Forty-nine adults with DS aged 25-65 underwent positron emission tomography with Pittsburgh compound-B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. RESULTS: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. DISCUSSION: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.This research was generously supported by a grant from the Medical Research Council (grant ID number: 98480). Additional support came from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, The Down Syndrome Association, and The Health Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jalz.2015.07.49

Gain-of-Function R225W Mutation in Human AMPKγ3 Causing Increased Glycogen and Decreased Triglyceride in Skeletal Muscle

BACKGROUND: AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory gamma(3) subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations. Here we report the first gain-of-function mutation in the muscle-specific regulatory gamma(3) subunit in humans. METHODS AND FINDINGS: We sequenced the exons and splice junctions of the AMPK gamma(3) gene (PRKAG3) in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The gamma(3) R225W mutation is homologous in location to the gamma(2)R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the gamma(3)R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN-) pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a approximately 90% increase of skeletal muscle glycogen content and a approximately 30% decrease in intramuscular triglyceride (IMTG). CONCLUSIONS: We have identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3) subunit of AMPK in humans. The gamma(3)R225W mutation has significant functional effects as demonstrated by increases in basal and AMP-activated AMPK activities, increased muscle glycogen and decreased IMTG. Overall, these findings are consistent with an important regulatory role for AMPK gamma(3) in human muscle energy metabolism

Correlation of Global and Gene-Specific DNA Methylation in Maternal-Infant Pairs

The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: β = 0.63, p<0.0001; Alu: β = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (β = 0.43, p = <0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention