A multiple testing procedure for multi-dimensional pairwise comparisons with application to gene expression studies

Figure S1. A graphical display of various hypotheses of interest. (TIFF 149 kb

Mycoplasma Suppression of THP-1 Cell TLR Responses Is Corrected with Antibiotics

Mycoplasma contamination of cultured cell lines is a serious problem in research, altering cellular response to different stimuli thus compromising experimental results. We found that chronic mycoplasma contamination of THP-1 cells suppresses responses of THP-1 cells to TLR stimuli. For example, E. coli LPS induced IL-1 β was suppressed by 6 fold and IL-8 by 10 fold in mycoplasma positive THP-1 cells. Responses to live F. novicida challenge were suppressed by 50-fold and 40-fold respectively for IL-1β and IL-8. Basal TLR4 expression level in THP-1 cells was decreased by mycoplasma by 2.4-fold (p = 0.0003). Importantly, cell responses to pathogen associated molecular patterns are completely restored by mycoplasma clearance with Plasmocin. Thus, routine screening of cell lines for mycoplasma is important for the maintenance of reliable experimental data and contaminated cell lines can be restored to their baseline function with antibiotic clearance of mycoplasma

Adoption of social media marketing for sustainable business growth of SMEs in emerging economies: The moderating role of leadership support

Social media marketing (SMM) plays an important role in business communication, mar-keting, operations, and other activities. There is a growing interest among researchers, academicians, and practitioners to understand the role of SMM in business sustainability in small and medium enterprises (SMEs) in an emerging economy, like India. Few studies have attempted to understand this role. Thus, the aim of this study is to examine the impact of adopting social media marketing for sustainable business growth of SMEs in an emerging economy. The study also investigates the moderating role of SME leadership support on the relationship between SMM usage and sustainable business growth of SMEs. After reviewing the existing literature and technology adoption model, a theoretical model is developed, which is then validated using a structural equation modeling tech-nique to analyze 304 samples of Indian SMEs that use different social media marketing applications in their enterprises. This study confirmed that SMM tools significantly and positively improve the sustainable growth of SMEs in an emerging economy. Additionally, the study also found that SME leadership team plays a vital role in supporting actual usage of SMM tools that accelerate sustainable business growth of SMEs

Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPR(mt) to promote metastasis

By causing mitochondrial DNA (mtDNA) mutations and oxidation of mitochondrial proteins, reactive oxygen species (ROS) leads to perturbations in mitochondrial proteostasis. Several studies have linked mtDNA mutations to metastasis of cancer cells but the nature of the mtDNA species involved remains unclear. Our data suggests that no common mtDNA mutation identifies metastatic cells; rather the metastatic potential of several ROS-generating mutations is largely determined by their mtDNA genomic landscapes, which can act either as an enhancer or repressor of metastasis. However, mtDNA landscapes of all metastatic cells are characterized by activation of the SIRT/FOXO/SOD2 axis of the mitochondrial unfolded protein response (UPR(mt)). The UPR(mt) promotes a complex transcription program ultimately increasing mitochondrial integrity and fitness in response to oxidative proteotoxic stress. Using SOD2 as a surrogate marker of the UPR(mt), we found that in primary breast cancers, SOD2 is significantly increased in metastatic lesions. We propose that the ability of selected mtDNA species to activate the UPR(mt) is a process that is exploited by cancer cells to maintain mitochondrial fitness and facilitate metastasis.Oncogene advance online publication, 3 April 2017; doi:10.1038/onc.2017.52

Generating Optimal Topologies in Structural Design Using a Homogenization Method,"

This paper proposes a basic method for designing light and rigid structures that have a maximum natural frequency for a designated mode. A design variable "density," related to the material properties of a three-dimensional solid element, is introduced into the finite element method ( FEM ). Thus, a structure is expressed as a density distribution inside its design domain, and the optimal structure is obtained by searching for the most suitable such distribution

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia:A multi-national study

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, &gt;400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC &gt;400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC &gt;400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC &gt;400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.</p