Effect of age and gender on serum periostin: Relationship to cortical measures, bone turnover and hormones

Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16–18 years), peak bone mass (30–32 years) and older age (over 70 years). We measured serum periostin with a new ELISA optimised for human serum and plasma which recognises all known splice variants (Biomedica). We measured the distal radius and distal tibia with HR-pQCT, and measured serum PINP, CTX, sclerostin, PTH, IGF-1, estradiol and testosterone. Periostin was higher at age 16–18 than age 30–32 (1253 vs 842 pmol/l, p < 0.001), but not different between age 30–32 and over age 70. Periostin was inversely correlated with tibia cortical thickness and density (R − 0.229, − 0.233, both p = 0.003). It was positively correlated with PINP (R 0.529, p < 0.001), CTX (R 0.427, p < 0.001) and IGF-1 (R 0.440, p < 0.001). When assessed within each age group these correlations were only significant at age 16–18, except for PINP which was also significant over age 70. We conclude that periostin may have a role in IGF-1 driven cortical modeling and consolidation in young adults, but it may not be an important mediator in older adults

Triboelectric Charging Properties of the Functional Groups of Common Pharmaceutical Materials Using Density Functional Theory Calculations

Triboelectrification is a ubiquitous and poorly understood phenomenon in powder processing, particularly for pharmaceutical powders. Charged particles can adhere to vessel walls, causing sheeting; they can also cause agglomeration, threatening the stability of powder formulations, and in extreme cases electrostatic discharges, which present a serious fire and explosion hazard. Triboelectrification is highly sensitive to environmental and material conditions, which makes it very difficult to compare experimental results from different publications. In this work, density functional theory (DFT) is used to investigate the charge transfer characteristics of several functional groups of paracetamol in order to better understand the mechanisms of charging at the nanoscale and the influence of the environmental and material properties on charge transfer. This is achieved by studying the structure and electronic properties at the molecule–substrate interface. Using this molecule–substrate approach, the charging contributions of individual functional groups are explored by examining the Hirschfeld charges, the charge density difference between the molecule and substrate, the density of states, and the location of the frontier orbitals (HOMO and LUMO) of a paracetamol molecule. Charge density difference calculations indicate a significant transfer of charge from the molecule to the surface. Observable regions of electron density enrichment and depletion are evident around the electron-donating and -withdrawing groups, respectively. The density of states for the paracetamol molecule evolves as it approaches the surface, and the band gap disappears upon contact with the substrate. Hirshfeld charge analysis reveals asymmetry in the charge redistribution around the molecule, highlighting the varying charging tendencies of different atoms

D-term Inflation in Superstring Theories

An inflationary stage dominated by a $D$-term avoids the slow-roll problem of inflation in supergravity and may emerge in theories with a non-anomalous or anomalous U(1) gauge symmetry. The most intriguing and commonly invoked possibility is that the Fayet-Iliopoulos $D$-term triggering inflation is the one emerging in superstring theories. We discuss the complications one has to face when trying to build up a successful $D$-term inflationary scenario in superstring models. In particular, we show that the ``vacuum shifting'' phenomenon of string theories is usually very efficient even in the early Universe, thus preventing inflation from taking place. On the other hand, when $D$-term inflation is free to occur, the presence of a plethora of fields and several non-anomalous additional abelian symmetries in string theories may help in reconciling the value of the Fayet-Iliopoulos $D$-term required by the COBE normalization with the value predicted by string theories. We also show that in superstring $D$-term inflation gravitinos are likely to pose no cosmological problem.Comment: 19 pages, LaTeX fil

Unitary designs and codes

A unitary design is a collection of unitary matrices that approximate the entire unitary group, much like a spherical design approximates the entire unit sphere. In this paper, we use irreducible representations of the unitary group to find a general lower bound on the size of a unitary t-design in U(d), for any d and t. We also introduce the notion of a unitary code - a subset of U(d) in which the trace inner product of any pair of matrices is restricted to only a small number of distinct values - and give an upper bound for the size of a code of degree s in U(d) for any d and s. These bounds can be strengthened when the particular inner product values that occur in the code or design are known. Finally, we describe some constructions of designs: we give an upper bound on the size of the smallest weighted unitary t-design in U(d), and we catalogue some t-designs that arise from finite groups.Comment: 25 pages, no figure

Tracking Black Holes in Numerical Relativity

This work addresses and solves the problem of generically tracking black hole event horizons in computational simulation of black hole interactions. Solutions of the hyperbolic eikonal equation, solved on a curved spacetime manifold containing black hole sources, are employed in development of a robust tracking method capable of continuously monitoring arbitrary changes of topology in the event horizon, as well as arbitrary numbers of gravitational sources. The method makes use of continuous families of level set viscosity solutions of the eikonal equation with identification of the black hole event horizon obtained by the signature feature of discontinuity formation in the eikonal's solution. The method is employed in the analysis of the event horizon for the asymmetric merger in a binary black hole system. In this first such three dimensional analysis, we establish both qualitative and quantitative physics for the asymmetric collision; including: 1. Bounds on the topology of the throat connecting the holes following merger, 2. Time of merger, and 3. Continuous accounting for the surface of section areas of the black hole sources.Comment: 14 pages, 16 figure

Use of Coronary Computed Tomographic Angiography to guide management of patients with coronary disease

Background In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). Objectives The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. Methods In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Results Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95$303 to $621). Conclusions In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590

High-Throughput Screening for RecA Inhibitors Using a Transcreener Adenosine 5′- O -Diphosphate Assay

The activities of the bacterial RecA protein are involved in the de novo development and transmission of antibiotic resistance genes, thus allowing bacteria to overcome the metabolic stress induced by antibacterial agents. RecA is ubiquitous and highly conserved among bacteria, but has only distant homologs in human cells. Together, this evidence points to RecA as a novel and attractive antibacterial drug target. All known RecA functions require the formation of a complex formed by multiple adenosine 5′-O-triphosphate (ATP)-bound RecA monomers on single-stranded DNA. In this complex, RecA hydrolyzes ATP. Although several methods for assessing RecA's ATPase activity have been reported, these assay conditions included relatively high concentrations of enzyme and ATP and thereby restricted the RecA conformational state. Herein, we describe the validation of commercial reagents (Transcreener® adenosine 5′-O-diphosphate [ADP]2 fluorescence polarization assay) for the high-throughput measurement of RecA's ATPase activity with lower concentrations of ATP and RecA. Under optimized conditions, ADP detection by the Transcreener reagent provided robust and reproducible activity data (Z′=0.92). Using the Transcreener assay, we screened 113,477 small molecules against purified RecA protein. In total, 177 small molecules were identified as confirmed hits, of which 79 were characterized by IC50 values ≤10 μM and 35 were active in bioassays with live bacteria. This set of compounds comprises previously unidentified scaffolds for RecA inhibition and represents tractable hit structures for efforts aimed at tuning RecA inhibitory activity in both biochemical and bacteriological assays