Increased sclerostin associated with stress fracture of the third metacarpal bone in the Thoroughbred Racehorse

Abstract Objectives: The exact aetiopathogenesis of microdamage induced long bone fractures remains unknown. These fractures are likely the result of inadequate bone remodeling in response to damage. This study aims to identifiesy an association of osteocyte apoptosis, the presence of osteocytic osteolysis and any alterations in sclerostin expression with fracture of the third metacarpal bone of (Mc-III) thoroughbred (TB) racehorses. Methods: 30 Mc-III bones were obtained; 10 from bones fractured during racing, 10 from the contralateral limb and 10 from control horses. Each Mc- III bone was divided into fracture site, condyle, condylar groove and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase -13 (MMP-13), HtrA1 and sclerostin expression was analysed. of apoptotic cells between contralateral limb and unraced control, however, there were significantly less apoptotic cells in fractured samples (p<0.02). Immunohistochemistry showed that in the deep zones of the fractured samples sclerostin expression was significantly higher (p<0.03) of the total number of osteocytes. No increase in cathepsin K, MMP-13 or HtrA1 was present

Prospective Evaluation of Cardiopulmonary Resuscitation Performed in Dogs and Cats According to the RECOVER Guidelines. Part 1: Prognostic Factors According to Utstein-Style Reporting.

Factors associated with positive cardiopulmonary resuscitation (CPR) outcomes defined according to the veterinary Utstein-style CPR reporting guidelines have not been described since implementation of the Reassessment Campaign on Veterinary Resuscitation (RECOVER) CPR clinical guidelines in 2012. The aims of this study were to assess factors associated with positive CPR outcomes at a U.S. veterinary teaching hospital, to re-evaluate these factors since implementation of the RECOVER guidelines compared to reported factors prior to their publication, and to identify potential additional factors since guideline publication. One-hundred and seventy-two dogs and 47 cats that experienced cardiopulmonary arrest (CPA) and had CPR performed were prospectively included in this observational study. Supervising clinicians were asked to complete a data form on CPR events immediately following completion of CPR efforts. Multivariable logistic regression was used to evaluate the effect of twenty hospital, animal, and arrest variables on the three patient outcomes "any return of spontaneous circulation (ROSC)," "sustained ROSC," and survival to hospital discharge. Cats had significantly higher odds to achieve any ROSC [OR (95%CI) 2.72 (1.12-6.61), p = 0.028] and survive to hospital discharge than dogs [OR (95%CI) 4.87 (1.52-15.58), p = 0.008]. Patients had significantly lower odds of achieving any ROSC if CPA occurred during nighttime hours [OR (95%CI) nighttime = 0.52 (0.27-0.98), p = 0.043], and higher odds if CPA was witnessed [OR (95%CI) 3.45 (1.57-7.55), p = 0.002], if less people were involved in CPR efforts [OR (95%CI) 0.8 (0.66-0.96), p = 0.016], if pulses were palpable during CPR [OR (95%CI) 9.27 (4.16-20.63), p &lt; 0.0005], and if an IV catheter was already in place at the time of CPA [OR (95%CI) 5.07 (2.12-12.07), p = 0.0003]. Odds for survival to hospital discharge were significantly higher if less people were involved in CPR efforts [OR (95%CI) 0.65 (0.46-0.91), p = 0.013] and for patients of the anesthesia service [OR (95%CI) 14.82 (3.91-56.17), p = 0.00007]. Overall, factors associated with improved CPR outcomes have remained similar since incorporation of RECOVER guidelines into daily practice. Witnessed CPA events and high-quality CPR interventions were associated with positive patient outcomes, emphasizing the importance of timely recognition and initiation of CPR efforts. An optimal CPR team size has yet to be determined

Lorenz gauge gravitational self-force calculations of eccentric binaries using a frequency domain procedure

We present an algorithm for calculating the metric perturbations and gravitational self-force for extreme-mass-ratio inspirals (EMRIs) with eccentric orbits. The massive black hole is taken to be Schwarzschild and metric perturbations are computed in Lorenz gauge. The perturbation equations are solved as coupled systems of ordinary differential equations in the frequency domain. Accurate local behavior of the metric is attained through use of the method of extended homogeneous solutions and mode-sum regularization is used to find the self-force. We focus on calculating the self-force with sufficient accuracy to ensure its error contributions to the phase in a long term orbital evolution will be $\delta\Phi \lesssim 10^{-2}$ radians. This requires the orbit-averaged force to have fractional errors $\lesssim 10^{-8}$ and the oscillatory part of the self-force to have errors $\lesssim 10^{-3}$ (a level frequently easily exceeded). Our code meets this error requirement in the oscillatory part, extending the reach to EMRIs with eccentricities of $e \lesssim 0.8$, if augmented by use of fluxes for the orbit-averaged force, or to eccentricities of $e \lesssim 0.5$ when used as a stand-alone code. Further, we demonstrate accurate calculations up to orbital separations of $a \simeq 100 M$, beyond that required for EMRI models and useful for comparison with post-Newtonian theory. Our principal developments include (1) use of fully constrained field equations, (2) discovery of analytic solutions for even-parity static modes, (3) finding a pre-conditioning technique for outer homogeneous solutions, (4) adaptive use of quad-precision and (5) jump conditions to handle near-static modes, and (6) a hybrid scheme for high eccentricities

Regulation of the galactose pathway in Saccharomyces cerevisiae: induction of uridyl transferase mRNA and dependency on GAL4 gene function

In Saccharomyces cerevisiae, utilization of galactose requires four inducible enzyme activities. Three of these activities (galactose-1-phosphate uridyl transferase, EC 2.7.7.10; uridine diphosphogalactose 4-epimerase, EC 5.1.3.2; and galactokinase, EC 2.7.1.6) are specified by three tightly linked genes (GAL7, GAL10, and GAL1, respectively) on chromosome II, whereas the fourth, galactose transport, is specified by a gene (GAL2) located on chromosome XII. Although classic genetic analysis has revealed both positive and negative regulatory genes that coordinately affect the appearance of all four enzyme activities, neither the basic events leading to the appearance of enzyme activities nor the roles of the regulatory genes have yet been determined. Regulation of inducible enzyme activity could be mediated by events related to transcription, translation, or enzyme activation. For the purpose of studying galactose pathway induction and its regulation, we have developed an immunoprecipitation assay that enables us to detect the GAL7 specified uridyl transferase polypeptide in yeast extracts and among the polypeptides synthesized in an RNA-dependent in vitro translation system. Use of this immunoprecipitation assay in conjunction with in vivo labeling experiments demonstrates the presence of [(3)H]leucine-labeled transferase in extracts prepared from cells grown in galactose but not from cells grown in glucose. This galactose-specific induction of transferase polypeptide is mediated by the de novo appearance of a functional mRNA species whose synthetic capacity is detectable by the combination of in vitro translation and immunoprecipitation. The appearance of functional transferase mRNA depends on wild-type expression of the positive regulatory gene, GAL4. Cells carrying a nonsense (amber) mutation in the GAL4 gene fail to produce the transferase mRNA, whereas a nonsense suppressor of the GAL4 amber mutant regains the galactose-specific mRNA response. Our results establish that the induction of the GAL7 specified uridyl transferase activity is mediated by de novo appearance of a functional mRNA and that this galactose-specific response is dependent on a wild-type GAL4 gene product

Performance Impact of Deflagration to Detonation Transition Enhancing Obstacles

A sub-model is developed to account for the drag and heat transfer enhancement resulting from deflagration-to-detonation (DDT) inducing obstacles commonly used in pulse detonation engines (PDE). The sub-model is incorporated as a source term in a time-accurate, quasi-onedimensional, CFD-based PDE simulation. The simulation and sub-model are then validated through comparison with a particular experiment in which limited DDT obstacle parameters were varied. The simulation is then used to examine the relative contributions from drag and heat transfer to the reduced thrust which is observed. It is found that heat transfer is far more significant than aerodynamic drag in this particular experiment

The AMSC mobile satellite system

The American Mobile Satellite Consortium (AMSC) Mobile Satellite Service (MSS) system is described. AMSC will use three multi-beam satellites to provide L-band MSS coverage to the United States, Canada and Mexico. The AMSC MSS system will have several noteworthy features, including a priority assignment processor that will ensure preemptive access to emergency services, a flexible SCPC channel scheme that will support a wide diversity of services, enlarged system capacity through frequency and orbit reuse, and high effective satellite transmitted power. Each AMSC satellite will make use of 14 MHz (bi-directional) of L-band spectrum. The Ku-band will be used for feeder links

Extremely asymmetrical scattering in gratings with varying mean structural parameters

Extremely asymmetrical scattering (EAS) is an unusual type of Bragg scattering in slanted periodic gratings with the scattered wave (the +1 diffracted order) propagating parallel to the grating boundaries. Here, a unique and strong sensitivity of EAS to small stepwise variations of mean structural parameters at the grating boundaries is predicted theoretically (by means of approximate and rigorous analyses) for bulk TE electromagnetic waves and slab optical modes of arbitrary polarization in holographic (for bulk waves) and corrugation (for slab modes) gratings. The predicted effects are explained using one of the main physical reasons for EAS--the diffractional divergence of the scattered wave (similar to divergence of a laser beam). The approximate method of analysis is based on this understanding of the role of the divergence of the scattered wave, while the rigorous analysis uses the enhanced T-matrix algorithm. The effect of small and large stepwise variations of the mean permittivity at the grating boundaries is analysed. Two distinctly different and unusual patterns of EAS are predicted in the cases of wide and narrow (compared to a critical width) gratings. Comparison between the approximate and rigorous theories is carried out.Comment: 16 pages, 5 figure

Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG &gt; 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG &lt; 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P &lt; 0.0001) and SCAs (P &lt; 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility

Chimpanzees demonstrate individual differences in social information use

Studies of transmission biases in social learning have greatly informed our understanding of how behaviour patterns may diffuse through animal populations, yet within-species inter-individual variation in social information use has received little attention and remains poorly understood. We have addressed this question by examining individual performances across multiple experiments with the same population of primates. We compiled a dataset spanning 16 social learning studies (26 experimental conditions) carried out at the same study site over a 12-year period, incorporating a total of 167 chimpanzees. We applied a binary scoring system to code each participant’s performance in each study according to whether they demonstrated evidence of using social information from conspecifics to solve the experimental task or not (Social Information Score—‘SIS’). Bayesian binomial mixed effects models were then used to estimate the extent to which individual differences influenced SIS, together with any effects of sex, rearing history, age, prior involvement in research and task type on SIS. An estimate of repeatability found that approximately half of the variance in SIS was accounted for by individual identity, indicating that individual differences play a critical role in the social learning behaviour of chimpanzees. According to the model that best fit the data, females were, depending on their rearing history, 15–24% more likely to use social information to solve experimental tasks than males. However, there was no strong evidence of an effect of age or research experience, and pedigree records indicated that SIS was not a strongly heritable trait. Our study offers a novel, transferable method for the study of individual differences in social learning