Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full-thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro-fibrotic factors TGFβ1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars

Simulation of Light Antinucleus-Nucleus Interactions

Creations of light anti-nuclei (anti-deuterium, anti-tritium, anti-He3 and anti-He4) are observed by collaborations at the LHC and RHIC accelerators. Some cosmic ray experiments are aimed to find the anti-nuclei in cosmic rays. To support the experimental studies of the anti-nuclei a Monte Carlo simulation of anti-nuclei interactions with matter is implemented in the Geant4 toolkit. The implementation combines practically all known theoretical approaches to the problem of antinucleon-nucleon interactions.Comment: 8 pages, 5 figure

A Relational Event Approach to Modeling Behavioral Dynamics

This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).

Relativistic Heavy--Ion Collisions in the Dynamical String--Parton Model

We develop and extend the dynamical string parton model. This model, which is based on the salient features of QCD, uses classical Nambu-Got\=o strings with the endpoints identified as partons, an invariant string breaking model of the hadronization process, and interactions described as quark-quark interactions. In this work, the original model is extended to include a phenomenological quantization of the mass of the strings, an analytical technique for treating the incident nucleons as a distribution of string configurations determined by the experimentally measured structure function, the inclusion of the gluonic content of the nucleon through the introduction of purely gluonic strings, and the use of a hard parton-parton interaction taken from perturbative QCD combined with a phenomenological soft interaction. The limited number of parameters in the model are adjusted to $e^+e^-$ and $p$--$p$ data. Utilizing these parameters, the first calculations of the model for $p$--$A$ and $A$--$A$ collisions are presented and found to be in reasonable agreement with a broad set of data.Comment: 26 pages of text with 23 Postscript figures placed in tex

Evaluation of rate law approximations in bottom-up kinetic models of metabolism.

BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches

Lower Blood Calcium Associates with Unfavorable Prognosis and Predicts for Bone Metastasis in NSCLC

Ionized calcium was involved in various cellular signal pathways,and regulates many cellular processes, including those relevant to tumorigenesis. We hypothesis that imbalance of calcium homeostasis is correlated with development of lung carcinomas. We collected the clinical data of 1084 patients with non small cell lung cancer (NSCLC) treated in Shandong Provincial Hospital, Shandong University. Logistic regression was used to determine the association between calcium levels and clinical characteristics, and COX regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. Blood electrolytes were tested before treatment; and nearly 16% patients with NSCLC were complained with decreased blood calcium, which is more frequent than that in other electrolytes. Further, Multivariate logistic regression analysis disclosed that there were significant correlation between blood calcium decrease and moderate and poor differentiation (P = 0.012, OR = 1.926 (1.203–4.219)), squamous cell carcinoma (P = 0.024, OR = 1.968(1.094–3.540)), and bone metastasis (P = 0.032, OR = 0.396(0.235–0.669)). In multivariate COX regression analysis, advanced lymph node stage and decreased blood calcium were significantly and independent, unfavorable prognostic factors (P<0.001). Finally, the Kaplan-Meier Survival curve revealed that blood calcium decrease was associated with shorter survival (Log-rank; χ2 = 26.172,P<0.001). Our finding indicates that lower blood calcium levels are associated with a higher risk of unfavorable prognosis and bone metastasis of NSCLC

Disappearance of myocardial perfusion defects on prone SPECT imaging: Comparison with cardiac magnetic resonance imaging in patients without established coronary artery disease

<p>Abstract</p> <p>Background</p> <p>It is of great clinical importance to exclude myocardial infarction in patients with suspected coronary artery disease who do not have stress-induced ischemia. The diagnostic use of myocardial perfusion single-photon emission computed tomography (SPECT) in this situation is sometimes complicated by attenuation artifacts that mimic myocardial infarction. Imaging in the prone position has been suggested as a method to overcome this problem.</p> <p>Methods</p> <p>In this study, 52 patients without known prior infarction and no stress-induced ischemia on SPECT imaging were examined in both supine and prone position. The results were compared with cardiac magnetic resonance imaging (CMR) with delayed-enhancement technique to confirm or exclude myocardial infarction.</p> <p>Results</p> <p>There were 63 defects in supine-position images, 37 of which disappeared in the prone position. None of the 37 defects were associated with myocardial infarction by CMR, indicating that all of them represented attenuation artifacts. Of the remaining 26 defects that did not disappear on prone imaging, myocardial infarction was confirmed by CMR in 2; the remaining 24 had no sign of ischemic infarction but 2 had other kinds of myocardial injuries. In 3 patients, SPECT failed to detect small scars identified by CMR.</p> <p>Conclusion</p> <p>Perfusion defects in the supine position that disappeared in the prone position were caused by attenuation, not myocardial infarction. Hence, imaging in the prone position can help to rule out ischemic heart disease for some patients admitted for SPECT with suspected but not documented ischemic heart disease. This would indicate a better prognosis and prevent unnecessary further investigations and treatment.</p