Alterations in bone tissue composition during osteoporosis likely disrupt the mechanical environment of bone cells and may thereby initiate a mechanobiological response. It has proved challenging to ...characterize the mechanical environment of bone cells in vivo, and the mechanical environment of osteoporotic bone cells is not known. The objective of this research is to characterize the local mechanical environment of osteocytes and osteoblasts from healthy and osteoporotic bone in a rat model of osteoporosis. Using a custom-designed micromechanical loading device, we apply strains representative of a range of physical activity (up to 3000 με) to fluorescently stained femur samples from normal and ovariectomized rats. Confocal imaging was simultaneously performed, and digital image correlation techniques were applied to characterize cellular strains. In healthy bone tissue, osteocytes experience higher maximum strains (31,028 ± 4213 με) than osteoblasts (24,921 ± 3,832 με), whereas a larger proportion of the osteoblast experiences strains >10,000 με. Most interestingly, we show that osteoporotic bone cells experience similar or higher maximum strains than healthy bone cells after short durations of estrogen deficiency (5 weeks), and exceeded the osteogenic strain threshold (10,000 με) in a similar or significantly larger proportion of the cell (osteoblast, 12.68% vs. 13.68%; osteocyte, 15.74% vs. 5.37%). However, in long-term estrogen deficiency (34 weeks), there was no significant difference between bone cells in healthy and osteoporotic bone. These results suggest that the mechanical environment of bone cells is altered during early-stage osteoporosis, and that mechanobiological responses act to restore the mechanical environment of the bone tissue after it has been perturbed by ovariectomy.
Competition-driven repositioning Wang, Richard D.; Shaver, J. Myles
Strategic management journal,
November 2014, Letnik:
35, Številka:
11
Journal Article
Recenzirano
We study competition as an impetus for firms to reposition—to abandon their current positioning strategy and adopt a new one. We predict that as a strong firm moves closer, competition erodes the ...profitability of situated firms and prompts them to reposition. We expect this effect is pronounced the greater difference in competitive strength. However, we expect that countervailing forces exist such that the viability of alternative positions and the opportunity cost of abandoning a current position mitigate this effect. Evidence from a natural experiment in China's satellite television industry supports our hypotheses. This research adds to the existing literature on repositioning, which emphasizes the phenomenon as opportunity-driven, and to the competitive interaction literature, which typically does not distinguish between noncounterattack strategies.
Abstract
Motivation
While many pipelines have been developed for calling genotypes using RNA-sequencing (RNA-Seq) data, they all have adapted DNA genotype callers that do not model biases specific to ...RNA-Seq such as allele-specific expression (ASE).
Results
Here, we present Bayesian beta-binomial mixture model (BBmix), a Bayesian beta-binomial mixture model that first learns the expected distribution of read counts for each genotype, and then deploys those learned parameters to call genotypes probabilistically. We benchmarked our model on a wide variety of datasets and showed that our method generally performed better than competitors, mainly due to an increase of up to 1.4% in the accuracy of heterozygous calls, which may have a big impact in reducing false positive rate in applications sensitive to genotyping error such as ASE. Moreover, BBmix can be easily incorporated into standard pipelines for calling genotypes. We further show that parameters are generally transferable within datasets, such that a single learning run of less than 1 h is sufficient to call genotypes in a large number of samples.
Availability and implementation
We implemented BBmix as an R package that is available for free under a GPL-2 licence at https://gitlab.com/evigorito/bbmix and https://cran.r-project.org/package=bbmix with accompanying pipeline at https://gitlab.com/evigorito/bbmix_pipeline.
There is high demand for new methods to modify peptides, for application in drug discovery and biomedicine. A C–H functionalization protocol for the olefination of tryptophan residues in peptides is ...described. The modification is successful for Trp residues at any position in the peptide, has broad scope in the styrene coupling partner, and offers opportunities for conjugating peptides with other biomolecules. For peptides containing both Trp and Phe, directing group manipulation enables full control of residue selectivity.
Background
While surgery remains the mainstay of treatment for limb sarcoma, extreme old age is a relative contraindication to oncological surgery.
Methods
Patients >80 years referred with primary ...extremity soft-tissue sarcoma (ESTS) between 2007 and 2016 were retrospectively reviewed. Prognostic variables, including ASA status and Clinical Frailty Scores, were collected. Endpoints were perioperative morbidity, locoregional (LRR) and distant recurrence (DR), disease-specific survival (DSS) adjusted using competing risk modelling, and overall survival (OS).
Results
A total of 141 primary tumours were identified, with 116 undergoing resections. Main motives for nonoperative management were severe frailty or significant comorbidity (56.0%). The operative group had a median age of 84 (range 80-96) years and median follow-up of 16 months (range 0-95). 45.7% of patients received radiotherapy. Median hospital stay was 7 (range 0-40) days, with frailty (
p
= 0.25) and ASA (
p
= 0.28) not associated with prolonged admission. 12.9% developed significant complications, with one perioperative mortality.
24.1% had LRR, occurring at a median of 14.5 months. All patients with reported DR (28.4%), except one, died of their disease. Frailty did not confer a significant difference in adjusted LRFS (
p
= 0.95) and DMFS (
p
= 0.84). One- and 5-year adjusted DSS and OS was 87.0% versus 74.9% and 62.3% versus 27.4%, respectively. Frailty (CFS ≥4) was associated with worse OS (hazard ratio HR 2.49; 95% confidence interval CI 1.51-4.12;
p
< 0.001), however not with adjusted DSS (
p
= 0.16). Nonoperative management conferred a 1- and 5-year adjusted DSS was 58.3% and 44.4%, respectively.
Conclusions
Extremity surgery for sarcoma is well tolerated in the frail very elderly population with low morbidity and comparable oncological outcomes.
Boron monofluoride (BF) is a diatomic molecule with 10 valence electrons, isoelectronic to carbon monoxide (CO). Unlike CO, which is a stable molecule at room temperature and readily serves as both a ...bridging and terminal ligand to transition metals, BF is unstable below 1800°C in the gas phase, and its coordination chemistry is substantially limited. Here, we report the isolation of the iron complex Fe(BF)(CO)
(CNAr
)
Ar
, 2,6-(2,4,6-(
Pr)
C
H
C
H
;
-Pr,
-propyl, featuring a terminal BF ligand. Single-crystal x-ray diffraction as well as nuclear magnetic resonance, infrared, and Mössbauer spectroscopic studies on Fe(BF)(CO)
(CNAr
)
and the isoelectronic dinitrogen (N
) and CO complexes Fe(N
)(CO)
(CNAr
)
and Fe(CO)
(CNAr
)
demonstrate that the terminal BF ligand possesses particularly strong σ-donor and π-acceptor properties. Density functional theory and electron-density topology calculations support this conclusion.
This paper examines the conditions under which firms make long horizon investments (i.e., investments that take a long period of time to pay off). We predict firms are constrained from making long ...horizon investments when short-term performance is poor—and this effect is especially pronounced for young firms. Moreover, we argue that when managers hold high levels of exercisable stock options, their firms are less likely to make long-term investments. However, firms are more likely to pursue long horizon investments when managerial stock options are not yet exercisable. Based on analysis of investments made by cable television operators from 1972-1996, we find support for these predictions. In addition to enhancing our understanding of investment choices, these results—derived from the temporally focused analysis of an investment's payoff horizon—suggest that payoff horizon is an important investment attribute in its own right and should be analyzed distinctly from and in addition to other aspects of investments, such as expected return and risk.
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