It is common for linear regression models to be plagued with the problem of multicollinearity when two or more regressors are highly correlated. This problem results in unstable estimates of regression coefficients and causes some serious problems in validation and interpretation of the model. Different diagnostic measures are used to detect multicollinearity among regressors. Many statistical software and R packages provide few diagnostic measures for the judgment of multicollinearity. Most widely used diagnostic measures in these software are: coefficient of determination (R 2), variance inflation factor/tolerance limit (VIF/TOL), eigenvalues, condition number (CN) and condition index (CI) etc. In this manuscript, we present an R package, mctest, that computes popular and widely used multicollinearity diagnostic measures. The package also indicates which regressors may be the reason of collinearity among regressors. Brief introduction of collinearity Consider the conventional multiple linear regression equation y = Xβ + u, where y is an n × 1 vector of observation on response variable, X is known design matrix of order n × p, β is an p × 1 vector of unknown parameters and u is an n × 1 vector of random errors with mean zero and variance σ 2 I n , where I n is an identity matrix of order n. One of the important assumptions of the classical linear regression model is that there is no exact collinearity among the regressors otherwise, the issue is referred to as multicollinearity. Generally, the problem of multicollinearity may also refer to have not only exact linear relationship but also high correlations among some or all regressors of a regression model under study. Strictly speaking, multicollinearity is usually refers to the existence of more than one exact linear relationship among regressors, while collinearity refers to the existence of a single linear relationship among regressors. However, in general, the term multicollinearity may be referred to both the cases. Data collection method, constraints on the fitted regression model, model specification error, overdefined model, some common trend in time series data and naturally correlated data may be some potential sources of multicollinearity.
Magnetorheological (MR) fluids are now well established as one of the leading materials for use in controllable structures and systems. Commercial application of MR fluids in various fields, particularly in the vibration control, has grown rapidly over the past few years. In this paper, properties of magnetorheological (MR) fluids ,its applications in suspensions of vehicles, suspension of trains, high buildings cable-stayed bridges have been discussed. The scope of MR fluids in future, problems and some suggestions are also presented. Finally, effectiveness of MR fluids in vibration control of marine diesel engine through experiment is briefly discussed by the author.
Upon activation, conventional T (Tconv) cells undergo an mTOR-driven glycolytic switch. Regulatory T (Treg) cells reportedly repress the mTOR pathway and avoid glycolysis. However, here we demonstrate that human thymusderived (t)Treg cells can become glycolytic in response to tumor necrosis factor receptor 2 (TNFR2) costimulation. This costimulus increases proliferation and induces a glycolytic switch in CD3-activated tTreg cells, but not in Tconv cells. Glycolysis in CD3/TNFR2-activated tTreg cells is driven by PI3-kinase/mTOR signaling and supports tTreg cell identity and suppressive function. Contrary to glycolytic Tconv cells, glycolytic tTreg cells do not show net lactate secretion and shuttle glucose-derived carbon into the tricarboxylic acid cycle. Ex vivo characterization of blood-derived TNFR2 high CD4 + CD25 high CD127 low effector T cells, which were FOXP3 + IKZF2 + , revealed an increase in glucose consumption and intracellular lactate levels, identifying them as glycolytic tTreg cells. Our study links TNFR2 costimulation in human tTreg cells to metabolic remodeling, providing an additional avenue for drug targeting.receptor 2 (TNFR2, TNFRSF1B, CD120b) costimulation in tTreg and Tconv cells. TNFR2 was previously shown to be important for Treg cell responses and protection against autoimmunity in human and mouse 30,31 and is considered a clinical target for selective Treg expansion or inhibition in transplant rejection, autoimmunity, or cancer 9, 10 . We here report that CD3-activated tTreg cells selectively respond to TNFR2 costimulation by proliferation and a PI3K/mTOR-driven glycolytic switch that is important for tTreg cell identity and function. We also identify unique elements of the glycolytic program in tTreg cells and validate our findings in tTreg cells directly isolated from human blood. RESULTS A novel strategy allows for stable human Treg cell expansion in the absence of rapamycinHuman Treg cells occur in low frequency in the blood and therefore, expansion protocols are used for clinical application 32 . In such protocols, Treg cells are flow cytometrically sorted and expanded in presence of the mTOR inhibitor rapamycin that selectively inhibits proliferation of contaminating Tconv cells 12 . However, since rapamycin affects many aspects of metabolism, these expansion protocols are not suitable to generate Treg cells for metabolic studies. Also, such cultures may still be contaminated with pTreg cells that can convert back to Tconv cells and confound data interpretation. We therefore employed a novel method to purify stable human tTreg cells, based on the marker glycoprotein (GP)A33 33 . Among CD4 + T cells, naïve Tconv cells were purified by flow cytometry on the basis of a CD25 low CD127 high CD45RA + GPA33 int phenotype and naïve tTreg cells on the basis of a CD25 high CD127 low CD45RA + GPA33 high phenotype (Extended Data Figure 1a). Phenotypic analysis of these populations indicated that the naïve tTreg cells could be discriminated from Tconv cells as previously defined 34 by expressi...
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