Additional file 1: Table S1 of Pan-cancer analysis of frequent DNA co-methylation patterns reveals consistent epigenetic landscape changes in multiple cancers

Frequent co-methylation clusters. Table S2. Cross-check of known tumor suppressor with corresponding cancer co-methylation clusters. The numbers indicate the overlaps between co-methylated clusters and known tumor suppressor in each corresponding cancer type. Freq ≥ 9 genes were obtained from combined co-methylated clusters from all 17 cancer datasets and extracted the genes appeared in over 9 datasets. Figure S1. Protein-protein network query on STRING database for Cluster 1 genes. (DOCX 375 kb

Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering

The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation

Table_1_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_3_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_2_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_4_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Additional file 2: of Identification of recurrent combinatorial patterns of chromatin modifications at promoters across various tissue types

Enriched GO terms for genes displaying CP2 at their promoters. (DOCX 15 kb

Synthesis of Degradable Organic Nanotubes by Bottlebrush Molecular Templating

Degradable organic nanotubes were synthesized by a single-molecule templating of core–shell bottlebrush copolymers composed of an etchable inner block (polylactide) and a functional outer block (poly­(styrene-<i>co</i>-maleic anhydride)). The pendant mercapto groups generated along the outer block chains by reacting the anhydride groups with cysteamine were oxidized to disulfide groups acting as degradable cross-linking units in the shell layer. Subsequent hydrolytic removal of the polyester inner core provided hollow organic nanotubes held together by disulfide groups as cross-linkers. The cleavage of disulfide linkers by reaction with dithiothreitol resulted in a complete disintegration of nanotube structures into small fragments

Deep 360° Optical Flow Estimation Based on Multi-Projection Fusion

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Environmentally Friendly Strategy for Treating In Situ Leaching Solutions of Ion-Adsorption Type Yttrium-Rich Heavy Rare-Earth Ore by a Bubble-Supported Organic Liquid Membrane

A novel environmentally friendly strategy based upon bubble-supported organic liquid membrane (BSOLM) extraction using saponified naphthenic acid as extractant is proposed in the present work for treating the in situ leaching solutions of ion-adsorption type yttrium-rich heavy rare-earth ores in South China. It was revealed that selectively preferential separation of non-yttrium rare earths from yttrium can be achieved, while the electrolyte aluminum salt can be retained in the raffinates for subsequent return as the leaching reagent for performing in situ leaching of ion-adsorption type heavy rare-earth ores. The BSOLM extraction exhibits an obvious advantage over conventional extraction in promoting the competitive mass transfer and separation of coexisting rare earths from yttrium and other non-rare-earth impurity ions. Using erbium as a representative of heavy rare earths, it was found that the differences in diffusive mass transfer rate of Er3+, Y3+, and Al3+ ions in the boundary layer of laminar flow near the surface of the extractant liquid membrane result in their enhanced separation. The BSOLM extraction prevents the convective disturbance along the normal vertical direction of the interface due to the irregular movement of dispersed oil droplets in the conventional extraction and therefore inhibit the co-extraction of Al3+ ions. The effects of Al3+ ion concentrations in aqueous feed solutions, initial aqueous pHs, concentrations of naphthenic acid, and its saponification degree on the separation efficiency were investigated. Experimental results confirmed that competitive hydration and adsorption of Al3+ ions at the interface play an important role in increasing the difference in concentration distribution of Er3+ and Y3+ ions near the interface during BSOLM extraction; therefore, the separation of rare earths from yttrium can be controllable