Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice

Objective. Osteoarthritis (OA) is a common chronic disease for which disease-modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain.Methods. Gait was monitored using a treadmill-based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments.Results. The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm . seconds(-1). Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant-induced arthritis.Conclusion. The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA.</p

Quantum corrections to broken N = 8 supergravity

We show that the one-loop effective potential of spontaneously broken N=8 supergravity is calculable and finite at all classical four-dimensional Minkowski vacua without tachyons in the spectrum. The reason is that the supertraces of the quadratic and quartic mass matrices vanish along the classically flat directions: Str M^2 = Str M^4 =0. We also show that Str M^6 = 0 but Str M^8 > 0 in a broad class of vacua with broken supersymmetry on a flat background, which includes all those explicitly identified so far. We find analytical and numerical evidence that the corresponding one-loop effective potential is negative-definite.Comment: 30 pages. v2: few misprints corrected. v3: JHEP published versio

Improving Retrieval Results with discipline-specific Query Expansion

Choosing the right terms to describe an information need is becoming more difficult as the amount of available information increases. Search-Term-Recommendation (STR) systems can help to overcome these problems. This paper evaluates the benefits that may be gained from the use of STRs in Query Expansion (QE). We create 17 STRs, 16 based on specific disciplines and one giving general recommendations, and compare the retrieval performance of these STRs. The main findings are: (1) QE with specific STRs leads to significantly better results than QE with a general STR, (2) QE with specific STRs selected by a heuristic mechanism of topic classification leads to better results than the general STR, however (3) selecting the best matching specific STR in an automatic way is a major challenge of this process.Comment: 6 pages; to be published in Proceedings of Theory and Practice of Digital Libraries 2012 (TPDL 2012

The Justified Ontology of Time

What are we justified in asserting when constructing an ontology of time? I believe a version of Presentism to be the only justified theory. ‘Justified’ here refers exclusively to a basis of empirical and epistemological evidence. What can we assert about the metaphysics of time when we start from a justificationist epistemology? Putnam and Rietdijk argue that the relativity of simultaneity supports Eternalism. My investigation examines the strength of justification Eternalism attains from the special theory of relativity (STR) and will argue that Eternalism is not justified by STR. I will also suggest that an alternative metaphysical theory of time, Point Presentism, attains justification from STR

"Moment-Based Estimation of Smooth Transition Regression Models with Endogenous Variables"

Nonlinear regression models have been widely used in practice for a variety of time series and cross-section datasets. For purposes of analyzing univariate and multivariate time series data, in particular, Smooth Transition Regression (STR) models have been shown to be very useful for representing and capturing asymmetric behavior. Most STR models have been applied to univariate processes, and have made a variety of assumptions, including stationary or cointegrated processes, uncorrelated, homoskedastic or conditionally heteroskedastic errors, and weakly exogenous regressors. Under the assumption of exogeneity, the standard method of estimation is nonlinear least squares. The primary purpose of this paper is to relax the assumption of weakly exogenous regressors and to discuss moment based methods for estimating STR models. The paper analyzes the properties of the STR model with endogenous variables by providing a diagnostic test of linearity of the underlying process under endogeneity, developing an estimation procedure and a misspecification test for the STR model, presenting the results of Monte Carlo simulations to show the usefulness of the model and estimation method, and providing an empirical application for inflation rate targeting in Brazil. We show that STR models with endogenous variables can be specified and estimated by a straightforward application of existing results in the literature.

Authentication of newly established human esophageal squamous cell carcinoma cell line (YM-1) using short tandem repeat (STR) profiling method

Cross-contamination during or early after establishment of a new cell line could result in the worldwide spread of a misidentified cell line. Therefore, newly established cell lines need to be authenticated by a reference standard method. This study was conducted to investigate the authenticity of a newly established epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM-1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC epithelial cells were cultured from the fresh tumor tissue of an adult female patient. Growth characteristics and epithelial originality of YM-1 cells were studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and ESCC donor tumor sample on two different days to prevent probable DNA contamination. STR profiling was performed using AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration as the passage number increases, STR profiling was performed again on harvested cells at passage 51. YM-1 cells grew as a monolayer with a population doubling time of 40.66Â h. Epithelial originality of YM-1 cells was confirmed using ICC/IF staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample was the same with YM-1 cells at passage 22. However, STR profile of the donor tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re-profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at D18S51 locus. This suggests that long-term culture of cell lines may alter their DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR profiling databases confirmed unique identity of YM-1 cell line. This study provides an easy, fast, and reliable procedure for authentication of newly established cell lines, which helps in preventing the spread of misidentified cells and improving the reproducibility and validity of experiments, consequently. © 2015, International Society of Oncology and BioMarkers (ISOBM)