•Investigation of robustness of a Generalized Quadratic Discriminant Analysis (GQDA) under the presence of Noise in data.•The GQDA is a novel approach integrating linear & quadratic discriminant ...analyses, but is extremely sensitive under mild contamination.•Development of roust versions of GQDA classier by using robust estimators of the mean vector and the dispersion matrix.•Detailed empirical comparison of robust GQDA proposals with 6 robust estimators, 3 classes of model distribution and 4 real data examples.
Quadratic discriminant analysis (QDA) is a widely used statistical tool to classify observations from different multivariate Normal populations. The generalized quadratic discriminant analysis (GQDA) classification rule/classifier, which generalizes the QDA and the minimum Mahalanobis distance (MMD) classifiers to discriminate between populations with underlying elliptically symmetric distributions competes quite favorably with the QDA classifier when it is optimal and performs much better when QDA fails under non-Normal underlying distributions with heavy tail, e.g. Cauchy distribution. However, the classification rule in GQDA is still based on the sample mean vector and the sample dispersion matrix of a training set, which are extremely non-robust under data contamination. In real world, however, it is quite common to face data which are highly vulnerable to outliers and so the lack of robustness of the classical estimators of the mean vector and the dispersion matrix reduces the efficiency of the GQDA classifier significantly, increasing the misclassification errors. The present paper investigates the performance of the GQDA classifier when the classical estimators of the mean vector and the dispersion matrix used therein are replaced by various robust counterparts. Applications to various real data sets as well as simulation studies reveal far better performance of the proposed robust versions of the GQDA classifier. A comparative study has been made to advocate the appropriate choice of the robust estimators to be used in a specific situation.
Mono‐ and dichloro acetamides were prepared via a hydrodechlorination reaction of trichloroacetamides under controlled electrochemical conditions. The reactions were carried out in an undivided cell ...with constant current flow using n‐Bu4NI as supporting electrolyte and methanol as solvent and proton source. Deuterodechlorination of trichloroacetamide was also successful when methanol‐d4 was used as solvent under identical electrochemical conditions.
Quadratic discriminant analysis (QDA) is a widely used statistical tool to classify observations from different multivariate Normal populations. The generalized quadratic discriminant analysis (GQDA) ...classification rule/classifier, which generalizes the QDA and the minimum Mahalanobis distance (MMD) classifiers to discriminate between populations with underlying elliptically symmetric distributions competes quite favorably with the QDA classifier when it is optimal and performs much better when QDA fails under non-Normal underlying distributions, e.g. Cauchy distribution. However, the classification rule in GQDA is based on the sample mean vector and the sample dispersion matrix of a training sample, which are extremely non-robust under data contamination. In real world, since it is quite common to face data highly vulnerable to outliers, the lack of robustness of the classical estimators of the mean vector and the dispersion matrix reduces the efficiency of the GQDA classifier significantly, increasing the misclassification errors. The present paper investigates the performance of the GQDA classifier when the classical estimators of the mean vector and the dispersion matrix used therein are replaced by various robust counterparts. Applications to various real data sets as well as simulation studies reveal far better performance of the proposed robust versions of the GQDA classifier. A Comparative study has been made to advocate the appropriate choice of the robust estimators to be used in a specific situation of the degree of contamination of the data sets.
How Salmonella enterica serovar Typhi (S. Typhi), an important human pathogen, survives the stressful microenvironments inside the gastrointestinal tract and within macrophages remains poorly ...understood. We report here that S. Typhi has a bonafide stringent response (SR) system, which is mediated by (p)ppGpp and regulates multiple virulence‐associated traits and the pathogenicity of the S. Typhi Ty2 strain. In an iron overload mouse model of S. Typhi infection, the (p)ppGpp0 (Ty2ΔRelAΔSpoT) strain showed minimal systemic spread and no mortality, as opposed to 100% death of the mice challenged with the isogenic wild‐type strain. Ty2ΔRelAΔSpoT had markedly elongated morphology with incomplete septa formation and demonstrated severely attenuated motility and chemotaxis due to the loss of flagella. Absence of the Vi‐polysaccharide capsule rendered the mutant strain highly susceptible to complement‐mediated lysis. The phenotypes of Ty2ΔRelAΔSpoT was contributed by transcriptional repression of several genes, including fliC, tviA, and ftsZ, as found by reverse transcriptase quantitative polymerase chain reaction and gene complementation studies. Finally, Ty2ΔRelAΔSpoT had markedly reduced invasion into intestinal epithelial cells and significantly attenuated survival within macrophages. To the best of our knowledge, this was the first study that addressed SR in S. Typhi and showed that (p)ppGpp was essential for optimal pathogenic fitness of the organism.
The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor (PPAR) α/γ ...agonist saroglitazar, has been approved. Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction.
RGS7 is elevated in the livers of NAFLD patients, particularly those with severe hepatic damage, pronounced insulin resistance, and high inflammation. In the liver, RGS7 forms a unique complex with transcription factor ATF3 and histone acetyltransferase Tip60, which is implicated in NAFLD. The removal of domains is necessary for ATF3/Tip60 binding compromises RGS7-dependent reactive oxygen species generation and cell death. Hepatic RGS7 knockdown (KD) prevented ATF3/Tip60 induction, and it provided protection against fibrotic remodeling and inflammation in high-fat diet-fed mice translating to improvements in liver function. Hyperlipidemia-dependent oxidative stress and metabolic dysfunction were largely reversed in RGS7 KD mice. Interestingly, saroglitazar failed to prevent RGS7/ATF3 upregulation but it did partially restore Tip60 levels. RGS7 drives the release of particularly tumor necrosis factor α (TNFα) from isolated hepatocytes, stellate cells and its depletion reverses steatosis, oxidative stress by direct TNFα exposure. Conversely, RGS7 overexpression in the liver is sufficient to trigger oxidative stress in hepatocytes that can be mitigated
TNFα inhibition.
We discovered a novel non-canonical function for an R7RGS protein, which usually functions to regulate G protein coupled receptor (GPCR) signaling. This is the first demonstration for a functional role of RGS7 outside the retina and central nervous system.
RGS7 represents a potential novel target for the amelioration of NAFLD.
38, 137-159.
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