Background and Purpose Several recent prospective studies have found that unruptured intracranial aneurysms (IAs) at various anatomical locations have different propensities for future rupture. However, there remains a lack of understanding regarding the rupture-prone characteristics, such as morphologic and hemodynamic factors, associated with different IA locations. Materials and Methods We investigated the characteristics of 311 unruptured aneurysms at our center. Based on the PHASES study, we separated and compared morphologic and hemodynamic characteristics among three aneurysm location groups: 1. internal carotid artery (ICA), 2. middle cerebral artery (MCA), and 3. anterior communicating (ACOM), posterior communicating (PCOM) and posterior circulation arteries. Results A mixed model statistical analysis showed that size ratio, low wall shear stress area and pressure loss coefficient were different between the IA location groups. Additionally, a pairwise comparison showed that ICA aneurysms had lower size ratios, lower wall shear stress areas and lower pressure loss coefficients compared to MCA aneurysms, and compared to the group of ACOM, PCOM and posterior circulation aneurysms. There was no statistical differences between MCA aneurysms and the group of ACOM, PCOM and posterior circulation aneurysms for morphologic or hemodynamic characteristics. Conclusions ICA aneurysms may be subjected to less rupture-prone morphologic and hemodynamic characteristics compared to other locations, which could explain the decreased rupture propensity of IAs at this location.

BACKGROUND AND PURPOSE:In patients with SAH with multiple intracranial aneurysms, often the hemorrhage pattern does not indicate the rupture source. Angiographic findings (intracranial aneurysm size and shape) could help but may not be reliable. Our purpose was to test whether existing parameters could identify the ruptured intracranial aneurysm in patients with multiple intracranial aneurysms and whether composite predictive models could improve the identification. MATERIALS AND METHODS:We retrospectively collected angiographic and medical records of 93 patients with SAH with at least 2 intracranial aneurysms (total of 206 saccular intracranial aneurysms, 93 ruptured), in which the ruptured intracranial aneurysm was confirmed through surgery or definitive hemorrhage patterns. We calculated 13 morphologic and 10 hemodynamic parameters along with location and type (sidewall/bifurcation) and tested their ability to identify rupture in the 93 patients. To build predictive models, we randomly assigned 70 patients to training and 23 to holdout testing cohorts. Using a linear regression model with a customized cost function and 10-fold cross-validation, we trained 2 rupture identification models: RIM C using all parameters and RIM M excluding hemodynamics. RESULTS:The 25 study parameters had vastly different positive predictive values (31%-87%) for identifying rupture, the highest being size ratio at 87%. RIM C incorporated size ratio, undulation index, relative residence time, and type; RIM M had only size ratio, undulation index, and type. During cross-validation, positive predictive values for size ratio, RIM M , and RIM C were 86% 6 4%, 90% 6 4%, and 93% 6 4%, respectively. In testing, size ratio and RIM M had positive predictive values of 85%, while RIM C had 92%. CONCLUSIONS:Size ratio was the best individual factor for identifying the ruptured aneurysm; however, RIM C , followed by RIM M , outperformed existing parameters.ABBREVIATIONS: AR ¼ aspect ratio; CFD ¼ computational fluid dynamics; D ¼ maximum diameter; H ¼ height (perpendicular); H max ¼ maximum height; IA ¼ intracranial aneurysm; NWSS ¼ normalized wall shear stress; OSI ¼ oscillatory shear index; RIM ¼ rupture identification model; RRS ¼ rupture resemblance score; RRT ¼ relative residence time; SR ¼ size ratio; UI ¼ undulation index; WSS ¼ wall shear stress

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H3K9me3 (histone H3 modified with tri-methylation at lysine 9) is a hallmark of transcriptional silencing and heterochromatin. However, its global effects on the genome, including euchromatin, are less well understood. Here we develop Formaldehyde-Assisted Identification of Regulatory Elements (FAIRE) for C. elegans to examine the chromatin configuration of mutants that lack virtually all H3K9me3, while leaving H3K9me1 and H3K9me2 intact. We find that nucleosomes are mildly disrupted, and levels of H3K9me2 and H3K27me3 rise in mutant embryos. In addition to these expected changes, the most dramatic change occurs in euchromatin: many regions encompassing transcription start sites (TSSs) gain an average of two nucleosomes in mutants. The affected regions normally lack H3K9me3, revealing a locus non-autonomous role for H3K9me3. Affected TSSs are associated with genes that are active in epithelia and muscles, and implicated in development, locomotion, morphogenesis and transcription. Mutant embryos develop normally under ideal laboratory conditions but die when challenged, with defects in morphogenesis and development. Our findings reveal that H3K9me3 protects transcription start sites within euchromatin from nucleosome deposition. These results may be relevant to mammals, where diseases that disrupt the nuclear lamina and heterochromatin can alter epithelial and muscle gene expression.

High-throughput sequencing technologies such as ChIPseq have deepened our understanding in many biological processes. De novo motif search is one of the key downstream computational analysis following the ChIP-seq experiments and several algorithms have been proposed for this purpose. However, most webbased systems do not perform independent filtering or enrichment analyses to ensure the quality of the discovered motifs. Here, we developed a web server Factorbook Motif Pipeline based on an algorithm used in analyzing ENCODE consortium ChIP-seq datasets. It performs comprehensive analysis on the set of peaks detected from a ChIP-seq experiments: (i) de novo motif discovery; (ii) independent composition and bias analyses and (iii) matching to the annotated motifs. The statistical tests employed in our pipeline provide a reliable measure of confidence as to how significant are the motifs reported in the discovery step. Availability: Factorbook Motif Pipeline source code is accessible through the following URL. https://github.com/joshuabhk/factorbookmotif-pipeline