1,567 research outputs found
THE EFFECT OF VARIOUS PATHOLOGIES ON BONE QUALITY
Boneâs ability to resist fracture is often ignored until a low-energy fracture occurs. Patients with Chronic Kidney Disease (CKD) or osteoporosis are at an increased risk of low-energy fracture. Generally, fracture risk is evaluated by using a bone mineral density (BMD) test. BMD values; however, do not fully predict boneâs ability to resist fracture. This suggests that other parameters may be involved. Bone quality is the term used to describe these parameters, which are categorized into three groups: structural, material, and microdamage. The aim of this dissertation research was to examine whether bone quality was altered in patients who: 1) had abnormal bone turnover (high or low) due to CKD, 2) suffered a low-energy fracture despite normal BMD, or 3) had osteoporosis and were treated with bisphosphonates. These studies used iliac crest bone specimens from Caucasian females aged 21 to 87 years. Boneâs material parameters were measured by Fourier transform infrared spectroscopy. The key finding from the turnover study was that high and low turnover was associated with altered bone quality. Specifically, bone with high turnover had a lower mineral-to-matrix ratio compared to normal and low turnover (p\u3c0.05), while low turnover had a lower cancellous bone volume and trabecular thickness compared to normal or high turnover (p\u3c0.05). The key finding from the fracture study was that patients with normal BMD and low-energy fractures had altered bone quality (greater collagen crosslinking ratio) compared to patients who had low-BMD with low-energy fractures and healthy subjects (controls) (p\u3c0.05). Lastly, the key findings from the bisphosphonate studies were that osteoporosis patients treated with these drugs had altered bone quality (specifically, greater (p\u3c0.05) mineral-to-matrix ratio) compared to untreated turnover-matched osteoporotic patients, and that were several positive linear correlations with the nanoindentation derived Youngâs modulus and hardness of cortical and trabecular bone and the duration of bisphosphonate treatment (p\u3c0.05). The findings presented provide further evidence that bone quantity is not the sole factor in determining boneâs ability to resist fractures and that bone quality is an essential factor
Phosphorylation of MCPH1 isoforms during mitosis followed by isoformâspecific degradation by APC/CâCDH1
Microcephalinâ1 (MCPH1) exists as 2 isoforms that regulate cyclinâdependent kinaseâ1 activation and chromosome condensation during mitosis, with MCPH1 mutations causing primary microcephaly. MCPH1 is also a tumor suppressor protein, with roles in DNA damage repair/checkpoints. Despite these important roles, there is little information on the cellular regulation of MCPH1. We show that both MCPH1 isoforms are phosphorylated in a cyclinâdependent kinaseâ1âdependent manner in mitosis and identify several novel phosphorylation sites. Upon mitotic exit, MCPH1 isoforms were degraded by the anaphaseâpromoting complex/cyclosomeâCDH1 E3 ligase complex. Anaphaseâpromoting complex/cyclosomeâCDH1 target proteins generally have DâBox or KENâBox degron sequences. We found that MCPH1 isoforms are degraded independently, with the long isoform degradation being DâBox dependent, whereas the short isoform was KENâBox dependent. Our research identifies several novel mechanisms regulating MCPH1 and also highlights important issues with several commercial MCPH1 antibodies, with potential relevance to previously published data.âMeyer, S. K., Dunn, M., Vidler, D. S., Porter, A., Blain, P. G., Jowsey, P. A. Phosphorylation of MCPH1 isoforms during mitosis followed by isoformâspecific degradation by APC/CâCDH1. FASEB J. 33, 2796â2808 (2019). www.fasebj.or
Temporal Evolution of Financial Market Correlations
We investigate financial market correlations using random matrix theory and
principal component analysis. We use random matrix theory to demonstrate that
correlation matrices of asset price changes contain structure that is
incompatible with uncorrelated random price changes. We then identify the
principal components of these correlation matrices and demonstrate that a small
number of components accounts for a large proportion of the variability of the
markets that we consider. We then characterize the time-evolving relationships
between the different assets by investigating the correlations between the
asset price time series and principal components. Using this approach, we
uncover notable changes that occurred in financial markets and identify the
assets that were significantly affected by these changes. We show in particular
that there was an increase in the strength of the relationships between several
different markets following the 2007--2008 credit and liquidity crisis.Comment: 15 pages, 10 figures, 1 table. Accepted for publication in Phys. Rev.
E. v2 includes additional section
The Empirics of Social Progress: The Interplay between Subjective Well-Being and Societal Performance
Though economists have long recognized that GDP is not by itself a measure of societal well-being, most GDP alternatives incorporate direct measures of economic performance. We propose instead an independently constructed measure, a social progress index, focusing exclusively on noneconomic dimensions of societal performance, highlighting three core dimensionsâbasic human needs, foundations of well-being, and opportunity. GDP and social progress are correlated but distinct, the social progress dimension least related to GDP (opportunity) is strongly related to subjective well-being, and the relationship between social progress and well-being is greater for individuals at lower relative income and educational attainment
Multiplexed Colorimetric Solid-Phase Extraction
Multiplexed colorimetric solid-phase extraction (MC-SPE) is an extension of colorimetric solid-phase extraction (C-SPE) an analytical platform that combines colorimetric reagents, solid phase extraction, and diffuse reflectance spectroscopy to quantify trace analytes in water. In CSPE, analytes are extracted and complexed on the surface of an extraction membrane impregnated with a colorimetric reagent. The analytes are then quantified directly on the membrane surface using a handheld diffuse reflectance spectrophotometer. Importantly, the use of solid-phase extraction membranes as the matrix for impregnation of the colorimetric reagents creates a concentration factor that enables the detection of low concentrations of analytes in small sample volumes. In extending C-SPE to a multiplexed format, a filter holder that incorporates discrete analysis channels and a jig that facilitates the concurrent operation of multiple sample syringes have been designed, enabling the simultaneous determination of multiple analytes. Separate, single analyte membranes, placed in a readout cartridge create unique, analyte-specific addresses at the exit of each channel. Following sample exposure, the diffuse reflectance spectrum of each address is collected serially and the Kubelka-Munk function is used to quantify each water quality parameter via calibration curves. In a demonstration, MC-SPE was used to measure the pH of a sample and quantitate Ag(I) and Ni(II)
Dynamic communities in multichannel data: An application to the foreign exchange market during the 2007--2008 credit crisis
We study the cluster dynamics of multichannel (multivariate) time series by
representing their correlations as time-dependent networks and investigating
the evolution of network communities. We employ a node-centric approach that
allows us to track the effects of the community evolution on the functional
roles of individual nodes without having to track entire communities. As an
example, we consider a foreign exchange market network in which each node
represents an exchange rate and each edge represents a time-dependent
correlation between the rates. We study the period 2005-2008, which includes
the recent credit and liquidity crisis. Using dynamical community detection, we
find that exchange rates that are strongly attached to their community are
persistently grouped with the same set of rates, whereas exchange rates that
are important for the transfer of information tend to be positioned on the
edges of communities. Our analysis successfully uncovers major trading changes
that occurred in the market during the credit crisis.Comment: 8 pages, 6 figures, accepted for publication in Chao
Synchrotron x-ray scattering of magnetic and electronic structure of UN and U2N3 epitaxial films
We examine the magnetic ordering of UN and of a closely related nitride,
U2N3, by preparing thin epitaxial films and using synchrotron x-ray techniques.
The magnetic configuration and subsequent coupling to the lattice are key
features of the electronic structure. The well-known antiferromagnetic (AF)
ordering of UN is confirmed, but the expected accompanying distortion at Tn is
not observed. Instead, we propose that the strong magneto-elastic interaction
at low temperature involves changes in the strain of the material. These
strains vary as a function of the sample form. As a consequence, the accepted
AF configuration of UN may be incorrect. In the case of cubic a-U2N3, no single
crystals have been previously prepared, and we have determined the AF ordering
wave-vector. The AF Tn is close to that previously reported. In addition,
resonant diffraction methods have identified an aspherical quadrupolar charge
contribution in U2N3 involving the 5f electrons; the first time this has been
observed in an actinide compound
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