Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

IntroductionPrevious studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury.MethodsNon-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption.ResultsμCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points.ConclusionsHigh-dose ALN treatment was able to prevent early trabecular bone loss and cartilage degeneration following non-invasive knee injury, but was not able to mitigate long-term joint degeneration. These data contribute to understanding the effect of bisphosphonates on the development of osteoarthritis, and may support the use of anti-resorptive drugs to prevent joint degeneration following injury, although further investigation is warranted

Occupational balance: What tips the scales for new students?

The open question, ‘What prevents you from reaching occupational balance?’, was posed within a questionnaire aimed at exploring the meanings of occupation, health and wellbeing with a cohort of first-year occupational therapy students during their initial few weeks at university. Their written responses to the question about occupational balance were analysed and are discussed in this paper. Not surprisingly, occupational balance appeared to be achieved by only a few and more by chance than design. People, time and money factors were identified as the main impediments to achieving occupational balance, with psychological and emotional pressures being at the forefront. Interestingly, despite these barriers, the overall educational benefit of considering the occupational balance question in this way raised the students’ awareness of its relationship to health and wellbeing. This increased awareness might have longer-term health benefits, both personally and professionally, which would be worthy of further research

The first high-amplitude delta Scuti star in an eclipsing binary system

We report the discovery of the first high-amplitude delta Scuti star in an eclipsing binary, which we have designated UNSW-V-500. The system is an Algol-type semi-detached eclipsing binary of maximum brightness V = 12.52 mag. A best-fitting solution to the binary light curve and two radial velocity curves is derived using the Wilson-Devinney code. We identify a late A spectral type primary component of mass 1.49+/-0.02 M_sun and a late K spectral type secondary of mass 0.33+/-0.02 M_sun, with an inclination of 86.5+/-1.0 degrees, and a period of 5.3504751+/-0.0000006 d. A Fourier analysis of the residuals from this solution is performed using PERIOD04 to investigate the delta Scuti pulsations. We detect a single pulsation frequency of f_1 = 13.621+/-0.015 c/d, and it appears this is the first overtone radial mode frequency. This system provides the first opportunity to measure the dynamical mass for a star of this variable type; previously, masses have been derived from stellar evolution and pulsation models.Comment: 7 pages, 6 figures, 2 tables, for submission to MNRAS, v2: paper size change, small typographical changes to abstrac

The ensemble of random Markov matrices

The ensemble of random Markov matrices is introduced as a set of Markov or stochastic matrices with the maximal Shannon entropy. The statistical properties of the stationary distribution pi, the average entropy growth rate $h$ and the second largest eigenvalue nu across the ensemble are studied. It is shown and heuristically proven that the entropy growth-rate and second largest eigenvalue of Markov matrices scale in average with dimension of matrices d as h ~ log(O(d)) and nu ~ d^(-1/2), respectively, yielding the asymptotic relation h tau_c ~ 1/2 between entropy h and correlation decay time tau_c = -1/log|nu| . Additionally, the correlation between h and and tau_c is analysed and is decreasing with increasing dimension d.Comment: 12 pages, 6 figur

A Mosaic of TESS Images Acquired Near The South Ecliptic Pole

The primary goal of the two-year Transiting Exoplanet Sky Survey (TESS) mission is to discover new, nearby exoplanet systems (Ricker et al. 2015). The mission acquires images every 30 minutes, through a single broadband filter and with four cameras. It offers a unique opportunity to study the diffuse universe. Holwerda (2018) showed it can in principle allow studies of topics such as the derivation of the halo mass profiles of nearby galaxies (essentially those in the NGC and UGC catalogs); tests of Lambda-CDM galaxy formation scenarios; derivation of stellar halo fractions for galaxies of different masses and morphologies; identification of local stellar streams that cross over multiple TESS observing sectors and other galaxy cannibalism leftovers; detection of ultra-diffuse galaxies as companions to bigger galaxies; and searches for supernovae remnants and planetary nebulae. With such science goals in mind, we have constructed a first-look, science-ready mosaic of a subset of the images released by TESS, to inform the processing and storage requirements of a mosaic of the southern sky, planned for Fall 2019. The mosaic covers the continuous viewing zone near the south ecliptic pole. In response to community requests, the mosaic is freely available at https://doi.org/10.26134/ExoFOP4 along with tools for downloading the data. This paper describes the creation of the mosaic and its characteristics

The combination of histone deacetylase inhibitors with immune-stimulating antibodies has potent anti-cancer effects

The use of immunotherapy to treat cancer is rapidly gaining momentum. Using pre-clinical mouse models, we have recently demonstrated potent and long lasting tumor regression can be elicited by immune-stimulating monoclonal antibodies (mAbs) when combined with histone deacetylase inhibitors (HDACi) and believe this therapy will have broad application in humans

Nonlinearity-induced conformational instability and dynamics of biopolymers

We propose a simple phenomenological model for describing the conformational dynamics of biopolymers via the nonlinearity-induced buckling and collapse (i.e. coiling up) instabilities. Taking into account the coupling between the internal and mechanical degrees of freedom of a semiflexible biopolymer chain, we show that self-trapped internal excitations (such as amide-I vibrations in proteins, base-pair vibrations in DNA, or polarons in proteins) may produce the buckling and collapse instabilities of an initially straight chain. These instabilities remain latent in a straight infinitely long chain, because the bending of such a chain would require an infinite energy. However, they manifest themselves as soon as we consider more realistic cases and take into account a finite length of the chain. In this case the nonlinear localized modes may act as drivers giving impetus to the conformational dynamics of biopolymers. The buckling instability is responsible, in particular, for the large-amplitude localized bending waves which accompany the nonlinear modes propagating along the chain. In the case of the collapse instability, the chain folds into a compact three-dimensional coil. The viscous damping of the aqueous environment only slows down the folding of the chain, but does not stop it even for a large damping. We find that these effects are only weakly affected by the peculiarities of the interaction potentials, and thus they should be generic for different models of semiflexible chains carrying nonlinear localized excitations.Comment: 4 pages (RevTeX) with 5 figures (EPS

Bubble generation in a twisted and bent DNA-like model

The DNA molecule is modeled by a parabola embedded chain with long-range interactions between twisted base pair dipoles. A mechanism for bubble generation is presented and investigated in two different configurations. Using random normally distributed initial conditions to simulate thermal fluctuations, a relationship between bubble generation, twist and curvature is established. An analytical approach supports the numerical results.Comment: 7 pages, 8 figures. Accepted for Phys. Rev. E (in press

Parametrically Excited Surface Waves: Two-Frequency Forcing, Normal Form Symmetries, and Pattern Selection

Motivated by experimental observations of exotic standing wave patterns in the two-frequency Faraday experiment, we investigate the role of normal form symmetries in the pattern selection problem. With forcing frequency components in ratio m/n, where m and n are co-prime integers, there is the possibility that both harmonic and subharmonic waves may lose stability simultaneously, each with a different wavenumber. We focus on this situation and compare the case where the harmonic waves have a longer wavelength than the subharmonic waves with the case where the harmonic waves have a shorter wavelength. We show that in the former case a normal form transformation can be used to remove all quadratic terms from the amplitude equations governing the relevant resonant triad interactions. Thus the role of resonant triads in the pattern selection problem is greatly diminished in this situation. We verify our general results within the example of one-dimensional surface wave solutions of the Zhang-Vinals model of the two-frequency Faraday problem. In one-dimension, a 1:2 spatial resonance takes the place of a resonant triad in our investigation. We find that when the bifurcating modes are in this spatial resonance, it dramatically effects the bifurcation to subharmonic waves in the case of forcing frequencies are in ratio 1/2; this is consistent with the results of Zhang and Vinals. In sharp contrast, we find that when the forcing frequencies are in ratio 2/3, the bifurcation to (sub)harmonic waves is insensitive to the presence of another spatially-resonant bifurcating mode.Comment: 22 pages, 6 figures, late

Professional Reading

Intelligence and Espionage: An Analytical Bibliography, and Scholar\u27s Guide to Intelligence Literature: Bibliography of the Russell J. Bowen Collectio