The variation of relative magnetic helicity around major flares

We have investigated the variation of magnetic helicity over a span of several days around the times of 11 X-class flares which occurred in seven active regions (NOAA 9672, 10030, 10314, 10486, 10564, 10696, and 10720) using the magnetograms taken by the Michelson Doppler Imager (MDI) on board the Solar and Heliospheric Observatory (SOHO). As a major result we found that each of these major flares was preceded by a significant helicity accumulation over a long period (0.5 to a few days). Another finding is that the helicity accumulates at a nearly constant rate and then becomes nearly constant before the flares. This led us to distinguish the helicity variation into two phases: a phase of monotonically increasing helicity and the following phase of relatively constant helicity. As expected, the amount of helicity accumulated shows a modest correlation with time-integrated soft X-ray flux during flares. However, the average helicity change rate in the first phase shows even stronger correlation with the time-integrated soft X-ray flux. We discuss the physical implications of this result and the possibility that this characteristic helicity variation pattern can be used as an early warning sign for solar eruptions

Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset

BACKGROUND: As more methods are developed to analyze RNA-profiling data, assessing their performance using control datasets becomes increasingly important. RESULTS: We present a 'spike-in' experiment for Affymetrix GeneChips that provides a defined dataset of 3,860 RNA species, which we use to evaluate analysis options for identifying differentially expressed genes. The experimental design incorporates two novel features. First, to obtain accurate estimates of false-positive and false-negative rates, 100-200 RNAs are spiked in at each fold-change level of interest, ranging from 1.2 to 4-fold. Second, instead of using an uncharacterized background RNA sample, a set of 2,551 RNA species is used as the constant (1x) set, allowing us to know whether any given probe set is truly present or absent. Application of a large number of analysis methods to this dataset reveals clear variation in their ability to identify differentially expressed genes. False-negative and false-positive rates are minimized when the following options are chosen: subtracting nonspecific signal from the PM probe intensities; performing an intensity-dependent normalization at the probe set level; and incorporating a signal intensity-dependent standard deviation in the test statistic. CONCLUSIONS: A best-route combination of analysis methods is presented that allows detection of approximately 70% of true positives before reaching a 10% false-discovery rate. We highlight areas in need of improvement, including better estimate of false-discovery rates and decreased false-negative rates

Multiscale Exploration of Mouse Brain Microstructures Using the Knife-Edge Scanning Microscope Brain Atlas

Connectomics is the study of the full connection matrix of the brain. Recent advances in high-throughput, high-resolution 3D microscopy methods have enabled the imaging of whole small animal brains at a sub-micrometer resolution, potentially opening the road to full-blown connectomics research. One of the first such instruments to achieve whole-brain-scale imaging at sub-micrometer resolution is the Knife-Edge Scanning Microscope (KESM). KESM whole-brain data sets now include Golgi (neuronal circuits), Nissl (soma distribution), and India ink (vascular networks). KESM data can contribute greatly to connectomics research, since they fill the gap between lower resolution, large volume imaging methods (such as diffusion MRI) and higher resolution, small volume methods (e.g., serial sectioning electron microscopy). Furthermore, KESM data are by their nature multiscale, ranging from the subcellular to the whole organ scale. Due to this, visualization alone is a huge challenge, before we even start worrying about quantitative connectivity analysis. To solve this issue, we developed a web-based neuroinformatics framework for efficient visualization and analysis of the multiscale KESM data sets. In this paper, we will first provide an overview of KESM, then discuss in detail the KESM data sets and the web-based neuroinformatics framework, which is called the KESM brain atlas (KESMBA). Finally, we will discuss the relevance of the KESMBA to connectomics research, and identify challenges and future directions

Specimen Preparation, Imaging, and Analysis Protocols for Knife-edge Scanning Microscopy

Major advances in high-throughput, high-resolution, 3D microscopy techniques have enabled the acquisition of large volumes of neuroanatomical data at submicrometer resolution. One of the first such instruments producing whole-brain-scale data is the Knife-Edge Scanning Microscope (KESM)7, 5, 9, developed and hosted in the authors' lab. KESM has been used to section and image whole mouse brains at submicrometer resolution, revealing the intricate details of the neuronal networks (Golgi)1, 4, 8, vascular networks (India ink)1, 4, and cell body distribution (Nissl)3. The use of KESM is not restricted to the mouse nor the brain. We have successfully imaged the octopus brain6, mouse lung, and rat brain. We are currently working on whole zebra fish embryos. Data like these can greatly contribute to connectomics research10; to microcirculation and hemodynamic research; and to stereology research by providing an exact ground-truth

Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Miyoshi myopathy (MM) is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR).</p> <p>Method</p> <p>Five consecutive MM patients (3 male) in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique.</p> <p>Results</p> <p>All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS) was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P < 0.0001, < 0.0001, 0.038 and 0.003, respectively). Four patients showed fibrosis by LGE. The reduced PSLS lesion detected by 2D strain tended to be in the same area as that which showed fibrosis by LGE.</p> <p>Conclusions</p> <p>Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.</p

An Integrated Strategy for Analyzing the Unique Developmental Programs of Different Myoblast Subtypes

An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets—based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes—provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system

Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

A closer look at the increase in suicide rates in South Korea from 1986–2005

<p>Abstract</p> <p>Background</p> <p>Suicide rates have recently been decreasing on average among OECD countries, but increasing trends have been detected in South Korea, particularly since the 1997 economic crisis. There have been no detailed analyses about the changes of the suicide rates over time periods in Korea. We examined trends in both absolute and proportional suicide rates over the time period of economic development, crisis, and recovery (1986 – 2005) as well as in birth cohorts from 1924 to 1978.</p> <p>Methods</p> <p>We used data on total mortality and suicide rates from 1986 to 2005 published online by the Korean National Statistical Office (NSO) and extracted data for individuals under 80 years old. The analyses of the trends for 1) the sex-age-specific total mortality rate, 2) the sex-age-specific suicide rate, and 3) the sex-age-specific proportional suicide rate in 1986–2005 were conducted. To demonstrate the birth cohort effect on the proportional suicide rate, the synthetic birth cohort from 1924 to 1978 from the successive cross-sectional data was constructed.</p> <p>Results</p> <p>Age standardized suicide rates in South Korea increased by 98% in men (from 15.3 to 30.3 per 100,000) and by 124% in women (from 5.8 to 13.0 per 100,000). In both genders, the proportional increase in suicide rates was more prominent among the younger group aged under 45, despite the absolute increase being attributed to the older group. There were distinct cohort effects underlying increasing suicide rates particularly among younger age groups.</p> <p>Conclusion</p> <p>Increasing suicide rates in Korea was composed of a greater absolute increase in the older group and a greater proportional increase in the younger group.</p

The impact of ownership structure on earnings quality: the case of South Korea

© 2018, Macmillan Publishers Ltd., part of Springer Nature. This paper investigates the impact of business group ownership structure on the quality of earnings reporting using data from South Korea. In addition, we investigate the impact of ownership disparity and family ownership on earnings quality reporting. Using a self-constructed earnings quality index as a measure of earnings quality, we found that business group ownership structure is significantly associated with higher earnings quality. The result suggests that strong monitoring mechanisms introduced by the government, which are necessary for credibility in external financial markets and beneficial to business group reputation, led to increased transparency in earnings reports. We also found that disparity in ownership between control and cash flow rights in firms, as well as family ownership in group firms, was both associated with lower earnings quality