Evaluating the Impacts of Sequencing Depth on Transcriptome Profiling in Human Adipose

Recent advances in RNA sequencing (RNA-Seq) have enabled the discovery of novel transcriptomic variations that are not possible with traditional microarray-based methods. Tissue and cell specific transcriptome changes during pathophysiological stress in disease cases versus controls and in response to therapies are of particular interest to investigators studying cardiometabolic diseases. Thus, knowledge on the relationships between sequencing depth and detection of transcriptomic variation is needed for designing RNA-Seq experiments and for interpreting results of analyses. Using deeply sequenced Illumina HiSeq 2000 101 bp paired-end RNA-Seq data derived from adipose of a healthy individual before and after systemic administration of endotoxin (LPS), we investigated the sequencing depths needed for studies of gene expression and alternative splicing (AS). In order to detect expressed genes and AS events, we found that ∼100 to 150 million (M) filtered reads were needed. However, the requirement on sequencing depth for the detection of LPS modulated differential expression (DE) and differential alternative splicing (DAS) was much higher. To detect 80% of events, ∼300 M filtered reads were needed for DE analysis whereas at least 400 M filtered reads were necessary for detecting DAS. Although the majority of expressed genes and AS events can be detected with modest sequencing depths (∼100 M filtered reads), the estimated gene expression levels and exon/intron inclusion levels were less accurate. We report the first study that evaluates the relationship between RNA-Seq depth and the ability to detect DE and DAS in human adipose. Our results suggest that a much higher sequencing depth is needed to reliably identify DAS events than for DE genes

M87: A Misaligned BL LAC?

The nuclear region of M87 was observed with the Faint Object Spectrograph (FOS) on the Hubble Space Telescope (HST) at 6 epochs, spanning 18 months, after the HST image quality was improved with the deployment of the corrective optics (COSTAR) in December 1993. From the FOS target acquisition data, we have established that the flux from the optical nucleus of M87 varies by a factor ~2 on time scales of ~2.5 months and by as much as 25% over 3 weeks, and remains unchanged (<= 2.5%) on time scales of ~1 day. The changes occur in an unresolved central region <= 5 pc in diameter, with the physical size of the emitting region limited by the observed time scales to a few hundred gravitational radii. The featureless continuum spectrum becomes bluer as it brightens while emission lines remain unchanged. This variability combined with the observations of the continuum spectral shape, strong relativistic boosting and the detection of significant superluminal motions in the jet, strongly suggest that M87 belongs to the class of BL Lac objects but is viewed at an angle too large to reveal the classical BL Lac properties.Comment: 12 pages, 3 Postscript figure

Domain Altering SNPs in the Human Proteome and Their Impact on Signaling Pathways

Single nucleotide polymorphisms (SNPs) constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall on protein domains, 3D structures that facilitate connectivity of proteins in cell signaling and metabolic pathways. We scanned the human proteome using the PROSITE web tool and identified proteins with SNP containing domains. We showed that SNPs that fall on protein domains are highly statistically enriched among SNPs linked to hereditary disorders and complex diseases. Proteins whose domains are dramatically altered by the presence of an SNP are even more likely to be present among proteins linked to hereditary disorders. Proteins with domain-altering SNPs comprise highly connected nodes in cellular pathways such as the focal adhesion, the axon guidance pathway and the autoimmune disease pathways. Statistical enrichment of domain/motif signatures in interacting protein pairs indicates extensive loss of connectivity of cell signaling pathways due to domain-altering SNPs, potentially leading to hereditary disorders

Grain refinement of magnesium alloys: a review of recent research, theoretical developments and their application

This paper builds on the ‘‘Grain Refinement of Mg Alloys’’ published in 2005 and reviews the grain refinement research onMg alloys that has been undertaken since then with an emphasis on the theoretical and analytical methods that have been developed. Consideration of recent research results and current theoretical knowledge has highlighted two important factors that affect an alloy’s as-cast grain size. The first factor applies to commercial Mg-Al alloys where it is concluded that impurity and minor elements such as Fe and Mn have a substantially negative impact on grain size because, in combination with Al, intermetallic phases can be formed that tend to poison the more potent native or deliberately added nucleant particles present in the melt. This factor appears to explain the contradictory experimental outcomes reported in the literature and suggests that the search for a more potent and reliable grain refining technology may need to take a different approach. The second factor applies to all alloys and is related to the role of constitutional supercooling which, on the one hand, promotes grain nucleation and, on the other hand, forms a nucleation-free zone preventing further nucleation within this zone, consequently limiting the grain refinement achievable, particularly in low solute-containing alloys. Strategies to reduce the negative impact of these two factors are discussed. Further, the Interdependence model has been shown to apply to a broad range of casting methods from slow cooling gravity die casting to fast cooling high pressure die casting and dynamic methods such as ultrasonic treatment

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

BIM-Based Dynamic Construction Safety Rule Checking Using Ontology and Natural Language Processing

Real-time identification and prevention of safety risks in dynamic construction activities are demanded by construction safety managers to cope with the growing complexity of the construction site. Most of the studies on BIM-based construction safety inspection and prevention use data from the planning and design stage. Meanwhile, safety managers still need to spend a lot of time gathering reports about construction safety risks in certain periods or areas from inferred results in BIM. Therefore, this paper proposed an automatic safety risk identification and prevention mechanism for the construction process by integrating a safety rule library based on ontology technology and Natural Language Processing. An automatic inspection mechanism integrating BIM and safety rules is constructed, and a presentation mechanism of intelligent detection results based on Natural Language Processing is designed. The construction process safety rule checking system was developed, and the effectiveness of the system was verified by a case study. The outcome of this paper contributes to the development and application of ontology in construction safety research, and the NLP-based safety rule checking result presentation will benefit safety inspectors and construction managers in practice