1,045 research outputs found
Indicators of replicative damage in equine tendon fibroblast monolayers
<p>Background:
Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it.</p>
<p>Results:
We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents.</p>
<p>Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress.</p>
<p>Conclusions:
Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled.</p>
Recommended from our members
Stabilization of in-tank residuals and external-tank soil contamination: FY 1997 interim report
This interim report evaluates various ways to stabilize decommissioned waste tanks and contaminated soils at the AX Tank Farm as part of a preliminary evaluation of end-state options for the Hanford tanks. Five technical areas were considered: (1) emplacement of smart grouts and/or other materials, (2) injection of chemical-getters into contaminated soils surrounding tanks (soil mixing), (3) emplacement of grout barriers under and around the tanks, (4) the use of engineered barriers over the tanks, and (5) the explicit recognition that natural attenuation processes do occur. Research topics are identified in support of key areas of technical uncertainty, in each of the five technical areas. Detailed cost/benefit analyses of the recommended technologies are not provided in this evaluation, performed by Sandia National Laboratories, Albuquerque, New Mexico
Recommended from our members
Regulatory issues associated with closure of the Hanford AX Tank Farm ancillary equipment
Liquid mixed, high-level radioactive waste has been stored in underground single-shell tanks at the US Department of Energy`s (DOE`s) Hanford Site. After retrieval of the waste from the single-shell tanks, the DOE will proceed with closure of the tank farm. The 241-AX Tank Farm includes four one-million gallon single-shell tanks in addition to sluice lines, transfer lines, ventilation headers, risers, pits, cribs, catch tanks, buildings, well and associated buried piping. This equipment is classified as ancillary equipment. This document addresses the requirements for regulatory close of the ancillary equipment in the Hanford Site 241-AX Tank Farm. The options identified for physical closure of the ancillary equipment include disposal in place, disposal in place after treatment, excavation and disposal on site in an empty single-shell tank, and excavation and disposal outside the AX Tank Farm. The document addresses the background of the Hanford Site and ancillary equipment in the AX Tank Farm, regulations for decontamination and decommissioning of radioactively contaminated equipment, requirements for the cleanup and disposal of radioactive wastes, cleanup and disposal requirements governing hazardous and mixed waste, and regulatory requirements and issues associated with each of the four physical closure options. This investigation was conducted by the Sandia National Laboratories, Albuquerque, New Mexico, during Fiscal Year 1998 for the Hanford Tanks Initiative Project
On the Relationship Between First Occupation and Current Occupational Status
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68361/2/10.1177_073088847400100402.pd
Nonlinear Volatility of River Flux Fluctuations
We study the spectral properties of the magnitudes of river flux increments,
the volatility. The volatility series exhibits (i) strong seasonal periodicity
and (ii) strongly power-law correlations for time scales less than one year. We
test the nonlinear properties of the river flux increment series by randomizing
its Fourier phases and find that the surrogate volatility series (i) has almost
no seasonal periodicity and (ii) is weakly correlated for time scales less than
one year. We quantify the degree of nonlinearity by measuring (i) the amplitude
of the power spectrum at the seasonal peak and (ii) the correlation power-law
exponent of the volatility series.Comment: 5 revtex pages, 6 page
The Health Belief Model Applied to Understanding Diabetes Regimen Compliance
Inadequate adherence to prescribed treatment plans is perhaps the most serious obstacle to achieving success ful therapeutic outcomes, and non compliance by diabetic patients is no exception. This is partly based on pa tients' realization that compliance does not necessarily result in lack of illness. A psychosocial framework for under standing patient compliance is the Health Belief Model, which is based upon the value an individual places on the identified goal and the likelihood that compliance will achieve that goal. This Model has been useful to explain noncompliance, to make an "educa tional diagnosis," and for designing compliance-enhancing interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68410/2/10.1177_014572178501100108.pd
Templates for Convex Cone Problems with Applications to Sparse Signal Recovery
This paper develops a general framework for solving a variety of convex cone
problems that frequently arise in signal processing, machine learning,
statistics, and other fields. The approach works as follows: first, determine a
conic formulation of the problem; second, determine its dual; third, apply
smoothing; and fourth, solve using an optimal first-order method. A merit of
this approach is its flexibility: for example, all compressed sensing problems
can be solved via this approach. These include models with objective
functionals such as the total-variation norm, ||Wx||_1 where W is arbitrary, or
a combination thereof. In addition, the paper also introduces a number of
technical contributions such as a novel continuation scheme, a novel approach
for controlling the step size, and some new results showing that the smooth and
unsmoothed problems are sometimes formally equivalent. Combined with our
framework, these lead to novel, stable and computationally efficient
algorithms. For instance, our general implementation is competitive with
state-of-the-art methods for solving intensively studied problems such as the
LASSO. Further, numerical experiments show that one can solve the Dantzig
selector problem, for which no efficient large-scale solvers exist, in a few
hundred iterations. Finally, the paper is accompanied with a software release.
This software is not a single, monolithic solver; rather, it is a suite of
programs and routines designed to serve as building blocks for constructing
complete algorithms.Comment: The TFOCS software is available at http://tfocs.stanford.edu This
version has updated reference
Counterfactual Thinking and Entrepreneurial Self‐Efficacy: The Moderating Role of Self‐Esteem and Dispositional Affect
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97291/1/etap472.pd
Relevance of nucleon spin in amplitude analysis of reactions pi(-)p->pi(0)pi(0)n and pi(-)p->eta eta n
The measurements of reactions and on polarized targets at CERN found a strong dependence of pion
production amplitudes on nucleon spin. Analyses of recent measurements of
reaction on unpolarized targets by GAMS
Collaboration at 38 GeV/c and BNL E852 Collaboration at 18 GeV/c use the
assumption that pion production amplitudes do not depend on nucleon spin, in
conflict with the CERN results on polarized targets. We show that measurements
of and on unpolarized
targets can be analysed in a model independent way in terms of 4 partial-wave
intensities and 3 independent interference phases in the mass region where -
and -wave dominate. We also describe model-independent amplitude analysis of
reaction measured on polarized target, both in the
absence and in the presence of -wave amplitudes. We suggest that high
statistics measurements of reactions and be made on polarized targets at Protvino IHEP and at BNL, and
that model-independent amplitude analyses of this polarized data be performed
to advance hadron spectroscopy on the level of spin dependent production
amplitudes.Comment: 54 page
- …