15 research outputs found
Co-occurrence and mutual exclusivity: what cross-cancer mutation patterns can tell us.
Cancer is the dysregulated proliferation of cells caused by acquired mutations in key driver genes. The most frequently mutated driver genes promote tumorigenesis in various organisms, cell types, and genetic backgrounds. However, recent cancer genomics studies also point to the existence of context-dependent driver gene functions, where specific mutations occur predominately or even exclusively in certain tumor types or genetic backgrounds. Here, we review examples of co-occurring and mutually exclusive driver gene mutation patterns across cancer genomes and discuss their underlying biology. While co-occurring driver genes typically activate collaborating oncogenic pathways, we identify two distinct biological categories of incompatibilities among the mutually exclusive driver genes depending on whether the mutated drivers trigger the same or divergent tumorigenic pathways. Finally, we discuss possible therapeutic avenues emerging from the study of incompatible driver gene mutations
Design of a High Performance Thin All-Solid-State Supercapacitor Mimicking the Active Interface of Its Liquid-State Counterpart
Here we report an all-solid-state
supercapacitor (ASSP) which closely mimics the electrode–electrolyte
interface of its liquid-state counterpart by impregnating polyaniline
(PANI)-coated carbon paper with polyvinyl alcohol-H<sub>2</sub>SO<sub>4</sub> (PVA-H<sub>2</sub>SO<sub>4</sub>) gel/plasticized polymer
electrolyte. The well penetrated PVA-H<sub>2</sub>SO<sub>4</sub> network
along the porous carbon matrix essentially enhanced the electrode–electrolyte
interface of the resulting device with a very low equivalent series
resistance (ESR) of 1 Ω/cm<sup>2</sup> and established an interfacial
structure very similar to a liquid electrolyte. The designed interface
of the device was confirmed by cross-sectional elemental mapping and
scanning electron microscopy (SEM) images. The PANI in the device
displayed a specific capacitance of 647 F/g with an areal capacitance
of 1 F/cm<sup>2</sup> at 0.5 A/g and a capacitance retention of 62%
at 20 A/g. The above values are the highest among those reported for
any solid-state-supercapacitor. The whole device, including the electrolyte,
shows a capacitance of 12 F/g with a significantly low leakage current
of 16 ÎĽA<sup>2</sup>. Apart from this, the device showed excellent
stability for 10000 cycles with a coulombic efficiency of 100%. Energy
density of the PANI in the device is 14.3 Wh/kg
Revisiting profile of deliberate self-harm at a tertiary care hospital after an interval of 10 years
The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes
We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes
The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes-Related Quantitative-Trait Loci
Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes–related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population