6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/-) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/- mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance

Religion, race and abstinence from drug use among American adolescents

https://deepblue.lib.umich.edu/bitstream/2027.42/137867/1/occ58.pd

Monte Carlo Eikonal Scattering

Monte Carlo evaluation is used to calculate heavy-ion elastic scattering including the center-of-mass correction and the Coulomb interaction.Angular distributions are presented for a number of nuclear pairs over a wide energy range using nucleon-nucleon scattering parameters taken from phase-shift analyses and densities from independent sources. A technique for the efficient expansion of the Glauber amplitude in partial waves is developed

Accounting students' expectations and transition experiences of supervised work experience

Political and economic discourses position employability as a responsibility of higher education, which utilise mechanisms such as supervised work experience (SWE) to embed employability into the undergraduate curriculum. However, sparse investigation of students' contextualised experiences of SWE results in little being known about the mechanisms through which students derive employability benefits from SWE. The aim of this study is to examine the impact of students' expectation and conception of workplace learning on their transition into SWE. Analysis of accounting students' experiences reveal two broad conceptions of workplace learning, the differing impacts of which on transition experience are explored using existing learning transfer perspectives. Students displaying the more common 'technical' conception construct SWE as an opportunity to develop technical, knowledge-based expertise and abilities that prioritize product-based or cognitive learning transfer. Students with an 'experiential' conception were found to construct SWE primarily as an experience through which the development of personal skills and abilities beyond technical expertise are prioritized using process-based or socio-cultural learning transfer. Further data analysis suggests that these two learning transfer approaches have differing impacts on students' employability development which may indicate a need for universities to consider how to develop appropriate student expectations of and approaches to SWE and meaningful support for students' SWE transition

Angular Dependence in Proton-Proton Correlation Functions in Central 40Ca+40Ca^{40}Ca+^{40}Ca and 48Ca+48Ca^{48}Ca+^{48}Ca Reactions

The angular dependence of proton-proton correlation functions is studied in central $^{40}Ca+^{40}Ca$ and $^{48}Ca+^{48}Ca$ nuclear reactions at E=80 MeV/A. Measurements were performed with the HiRA detector complemented by the 4$\pi$ Array at NSCL. A striking angular dependence in the laboratory frame is found within p-p correlation functions for both systems that greatly exceeds the measured and expected isospin dependent difference between the neutron-rich and neutron-deficient systems. Sources measured at backward angles reflect the participant zone of the reaction, while much larger sources observed at forward angles reflect the expanding, fragmenting and evaporating projectile remnants. The decrease of the size of the source with increasing momentum is observed at backward angles while a weaker trend in the opposite direction is observed at forward angles. The results are compared to the theoretical calculations using the BUU transport model.Comment: 8 pages, 3 figures, submitted to PR

Modified Quark-Meson Coupling Model for Nuclear Matter

The quark-meson coupling model for nuclear matter, which describes nuclear matter as non-overlapping MIT bags bound by the self-consistent exchange of scalar and vector mesons, is modified by introducing medium modification of the bag constant. We model the density dependence of the bag constant in two different ways: one invokes a direct coupling of the bag constant to the scalar meson field, and the other relates the bag constant to the in-medium nucleon mass. Both models feature a decreasing bag constant with increasing density. We find that when the bag constant is significantly reduced in nuclear medium with respect to its free-space value, large canceling isoscalar Lorentz scalar and vector potentials for the nucleon in nuclear matter emerge naturally. Such potentials are comparable to those suggested by relativistic nuclear phenomenology and finite-density QCD sum rules. This suggests that the reduction of bag constant in nuclear medium may play an important role in low- and medium-energy nuclear physics.Comment: Part of the text is reordered, revised version to appear in Phys. Rev. C. 19 pages, ReVTeX, 4 figures embedde

Solving the measurement problem: de Broglie-Bohm loses out to Everett

The quantum theory of de Broglie and Bohm solves the measurement problem, but the hypothetical corpuscles play no role in the argument. The solution finds a more natural home in the Everett interpretation.Comment: 20 pages; submitted to special issue of Foundations of Physics, in honour of James T. Cushin

Proton Drip-Line Calculations and the Rp-process

One-proton and two-proton separation energies are calculated for proton-rich nuclei in the region $A=41-75$. The method is based on Skyrme Hartree-Fock calculations of Coulomb displacement energies of mirror nuclei in combination with the experimental masses of the neutron-rich nuclei. The implications for the proton drip line and the astrophysical rp-process are discussed. This is done within the framework of a detailed analysis of the sensitivity of rp process calculations in type I X-ray burst models on nuclear masses. We find that the remaining mass uncertainties, in particular for some nuclei with $N=Z$, still lead to large uncertainties in calculations of X-ray burst light curves. Further experimental or theoretical improvements of nuclear mass data are necessary before observed X-ray burst light curves can be used to obtain quantitative constraints on ignition conditions and neutron star properties. We identify a list of nuclei for which improved mass data would be most important.Comment: 20 pages, 9 figures, 2 table

An immunohistochemical study of the localization and developmental expression of ghrelin and its functional receptor in the ovine placenta

<p>Abstract</p> <p>Background</p> <p>Ghrelin is an orexigenic hormone principally produced by the stomach, but also by numerous peripheral tissues including the placenta. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation, and has been suggested to play a role in the developmental growth of the fetoplacental unit. The placental expression of ghrelin and its role in ruminant species is not known. We tested the hypotheses that ghrelin and its functional receptor, GHSR-1a, are present in tissues of the ovine placenta, and that their expression is linked to the stage of development.</p> <p>Methods</p> <p>Antibodies raised against ghrelin and GHSR-1a were used in standard immunohistochemical protocols on placental tissues collected from pregnant ewes (n = 6 per gestational time point) at days 50, 80, 100, 128 and 135 of gestation (term ≈ day 145). Immunostaining for ghrelin and GHSR-1a was quantified using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference.</p> <p>Results</p> <p>Positive immunostaining for ghrelin was detected in ovine placentae at all gestational time points, with staining localized to the maternal epithelium, caruncle and trophectoderm. There was a significant effect of gestational age (p < 0.001) on the placental expression of ghrelin, with maximal levels at gestational day 80. GHSR-1a immunostaining was detected in the fetal trophectoderm at all time points. In contrast to the gestational pattern of ghrelin expression, there was no effect of gestational age on placental GHSR-1a immunoexpression.</p> <p>Conclusion</p> <p>Ghrelin and GHSR-1a are both present in the ovine placenta, and ghrelin displays a developmentally-related pattern of expression. Therefore, these data strongly suggest that the ghrelin system may have a role in feto-placental development in sheep.</p