BackgroundDNA methylation profiling reveals important differentially methylated regions (DMRs) of the genome that are altered during development or that are perturbed by disease. To date, few programs exist for regional analysis of enriched or whole-genome bisulfate conversion sequencing data, even though such data are increasingly common. Here, we describe an open-source, optimized method for determining empirically based DMRs (eDMR) from high-throughput sequence data that is applicable to enriched whole-genome methylation profiling datasets, as well as other globally enriched epigenetic modification data.ResultsHere we show that our bimodal distribution model and weighted cost function for optimized regional methylation analysis provides accurate boundaries of regions harboring significant epigenetic modifications. Our algorithm takes the spatial distribution of CpGs into account for the enrichment assay, allowing for optimization of the definition of empirical regions for differential methylation. Combined with the dependent adjustment for regional p-value combination and DMR annotation, we provide a method that may be applied to a variety of datasets for rapid DMR analysis. Our method classifies both the directionality of DMRs and their genome-wide distribution, and we have observed that shows clinical relevance through correct stratification of two Acute Myeloid Leukemia (AML) tumor sub-types.ConclusionsOur weighted optimization algorithm eDMR for calling DMRs extends an established DMR R pipeline (methylKit) and provides a needed resource in epigenomics. Our method enables an accurate and scalable way of finding DMRs in high-throughput methylation sequencing experiments. eDMR is available for download at http://code.google.com/p/edmr/.
The bis(silylene)-based SiC(sp 3 )Si pincer ligand N,N′-bis(LSi:)dipyrromethane [SiCH 2 Si] (L1; L = PhC(NtBu) 2 ) with a C(sp 3 ) atom anchor was synthesized, and its coordination chemistry to iron was studied. Two novel iron hydride complexes, [SiCHSi]Fe(H)(N 2 )(PMe 3 ) (1) and [SiCHSi]Fe(H)(PMe 3 ) 2 (2), were synthesized in the reaction of L1 with Fe(PMe 3 ) 4 via C(sp 3 )−H bond activation under different inert atmospheres (N 2 and argon). To the best of our knowledge, 1 and 2 are the first examples of a bis(silylene)-based hydrido pincer iron complex produced through activation of a C(sp 3 )−H bond. At the same time 1 is also the first example of a TM dinitrogen complex supported by a bis(silylene) ligand. The interconversion between 1 and 2 was achieved and monitored by operando IR and 31 P NMR spectra to understand the transformation from 1 to 2 from the viewpoint of kinetics. To our delight, 1 could effectively catalyze silylation of dinitrogen and gave the highest turnover number so far among all the Fe-catalyzed N 2 silylation systems at room temperature and under atmospheric dinitrogen.
Triarylboranes have attracted significantly increasing research interest as a remarkable class of photoelectronic π-electron materials. Because of the presence of vacant p orbital on the B center, the boryl group is a very unique electron acceptor that exhibits not only electron-accepting ability through p-π* conjugation but also high Lewis acidity to coordinate with Lewis bases and steric bulk arising from the aryl substituent on the B center to get enough kinetic stability. Thus, the incorporation of a trivalent B element into π-conjugated systems is an efficient strategy to tune the electronic and stereo structures and thus the photoelectronic properties of π-electron systems. When an electron-donating group, such as amino, is present, triarylboranes would likely display intramolecular charge-transfer transitions. These kinds of molecules are often highly emissive. In addition, the geometry of the molecules has a great impact on the emission properties. In this Forum Article, we herein describe our recent progress on the charge-transfer emitting triarylborane π-electron systems with novel geometries, which include the lateral boryl-substituted π-system with amino groups at the terminal positions, the o,o'-substituted biaryl π-system with boryl and amino groups at the o,o'-positions, a triarylborane-based BODIPY system, and a B,N/S-bridged ladder-type π-system. We mainly put the emphasis on the molecular design concept, structure-property relationships, intriguing emission properties and great applications of the corresponding triarylborane π-systems.
The purpose of the study is to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) with pingyangmycin-lipiodol emulsion for the treatment of symptomatic giant hepatic haemangioma. Four hospitals (The Second Hospital of Shandong University, Qilu Hospital of Shandong University, Shandong Provincial Hospital and Jinan Municipal Hospital) participated in this study during 2002-2012. A total of 836 patients with symptomatic giant haemangioma were treated with pingyangmycin-lipiodol emulsion via selective TACE. The patients were followed-up for 12 months-10 years. The effectiveness of the treatment was evaluated by symptom assessments and upper abdominal magnetic resonance imaging or computed tomography. TACE was successfully performed for a total of 1120 lesions in 836 patients. Success rate of the procedure was 100 %. The mean diameter of the haemangiomas was significantly reduced after the interventional therapy (mean diameter 9.6 ± 0.8 vs. 3.6 ± 0.5 cm; P < 0.05). Symptom relief was achieved in all the patients during the follow-up period. No mortality was identified. TACE with pingyangmycin-lipiodol emulsion is a safe, feasible, and effective treatment for the giant symptomatic hepatic haemangioma.
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