Kevin C.W. Chen

Extent of smoking and nicotine dependence in the United States : 1991-1993

Rates of nicotine dependence vary in different sociodemographic groups in the population. These group differences remain to be understood. The objective of this study is to specify the relationship between cigarette consumption and nicotine dependence and whether group differences are explained by quantity smoked or differential sensitivity to nicotine. The data used derived from National Household Surveys on Drug Abuse (1991-1993), multistage area probability samples of the US population 12 years old and over, and anonymous structured household interviews, considering subjects who were last-month smokers (12,550 White, 4903 Black, 4839 Hispanic). The main outcome measure was last-year nicotine dependence based on symptoms of dependence and drug-related problems approximating DSM-IV dependence criteria. Rates are higher among females than males, Whites than minorities and the lowest among older adults. Dependence rates increase sharply up to half a pack of cigarettes smoked per day. At higher quantities, the increased risk for dependence is minimal. The higher rate of dependence among females than males results from a greater number of symptoms at the same quantity smoked. The similarity of adolescent and middle-adult rates results from the fact that adolescents smoke significantly fewer cigarettes than adults, but experience higher rates of dependence at the same levels of use. Although adults 50 and over are the heaviest smokers, they experience the lowest rates of dependence because of hypothesized lower sensitivity to increased quantity of nicotine intake. The higher rates among Whites than Blacks appear to result from heavier smoking and greater sensitivity to nicotine effects. It was concluded that adolescents, women and Whites are particularly vulnerable to becoming dependent on nicotine. Group-specific thresholds may be more appropriate criteria than an absolute threshold to define the risk for nicotine dependence.

Trying to understand why horrible things happen: attribution, shame, and symptom development following sexual abuse.

This study concerns the nature of specific attributions for sexual abuse and their relation to psychological distress over time. Participants (80 children and 57 adolescents) were seen within 8 weeks of discovery of the abuse and 1 year later. They described why they believed the abuse happened, rated the extent to which internal and external attributions for the abuse event applied to them, and completed measures of general attribution style for everyday events, shame for the abuse, and symptoms of depression, PTSD, and self-esteem. Parents and teachers rated behavior problems. Abuse-specific internal attributions were consistently related to higher levels of psychopathology and were particularly important for predicting PTSD symptoms and parent and teacher reports of internalizing behavior problems, even after controlling for age, gender, abuse events, and general attributional style. Shame also was an important predictor of symptom level and mediated the relation between abuse-specific internal attributions and PTSD symptoms.

Evidence for the biogenesis of more than 1,000 novel human microRNAs

BackgroundMicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome.ResultsEmploying an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling, we devised a quantitative miRNA capture system. In a kidney cell system, 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain.ConclusionsIn summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.

Agency Costs of Free Cash Flow and the Effect of Shareholder Rights on the Implied Cost of Equity Capital

In this paper, we examine the effect of shareholder rights on reducing the cost of equity and the impact of agency problems from free cash flow (FCF) on this effect. We find that firms with strong shareholder rights have a significantly lower implied cost of equity after controlling for risk factors, price momentum, analysts’ forecast biases, and industry and year effects than do firms with weak shareholder rights. Further analysis shows that the effect of shareholder rights on reducing the cost of equity is significantly stronger for firms with more severe agency problems from FCFs.

Earnings Management and Capital Resource Allocation: Evidence from China's Accounting-based Regulation of Rights Issues

From 1996 to 1998, listed companies in China were required to achieve a minimum return on equity (ROE) of 10 percent in each of the previous three years before they could apply for permission to issue additional shares. Hence, there was a heavy concentration of ROEs in the area of just above 10 percent. This paper shows that earnings management is relatively easy to detect on Chinas standardized income statement. In the 1996-1998 period, Chinese regulators seem to have gradually increased their scrutiny of earnings management in the approval process, and improved their ability to identify firms that subsequently performed better. However, since this scrutiny was limited, many firms were still able to gain rights issues approval through earnings management. The study shows that these firms subsequently performed worse than those which did not employ such practices. Thus, capital resources might have been allocated better had the regulators examined more closely the management of earnings.

A comprehensive analysis of piRNAs from adult human testis and their relationship with genes and mobile elements

BackgroundPiwi-interacting RNAs (piRNAs) are a recently discovered class of small non-coding RNAs whose best-understood function is to repress mobile element (ME) activity in animal germline. To date, nearly all piRNA studies have been conducted in model organisms and little is known about piRNA diversity, target specificity and biological function in human.ResultsHere we performed high-throughput sequencing of piRNAs from three human adult testis samples. We found that more than 81% of the ~17 million putative piRNAs mapped to ~6,000 piRNA-producing genomic clusters using a relaxed definition of clusters. A set of human protein-coding genes produces a relatively large amount of putative piRNAs from their 3’UTRs, and are significantly enriched for certain biological processes, suggestive of non-random sampling by the piRNA biogenesis machinery. Up to 16% of putative piRNAs mapped to a few hundred annotated long non-coding RNA (lncRNA) genes, suggesting that some lncRNA genes can act as piRNA precursors. Among major ME families, young families of LTR and endogenous retroviruses have a greater association with putative piRNAs than other MEs. In addition, piRNAs preferentially mapped to specific regions in the consensus sequences of several ME (sub)families and some piRNA mapping peaks showed patterns consistent with the “ping-pong” cycle of piRNA targeting and amplification.ConclusionsOverall our data provide a comprehensive analysis and improved annotation of human piRNAs in adult human testes and shed new light into the relationship of piRNAs with protein-coding genes, lncRNAs, and mobile genetic elements in human.

Accounting Measures of Business Performance and Tobin's q Theory

In this paper, Tobins q theory is applied to evaluate the informativeness of the traditional accounting measures of business performance and the measures derived from the cash recovery rate (CRR). The informativeness is defined in terms of the correlation of the performance measure and the internal rate of return implied in a ratio known as Tobins q. The paper shows that the traditional ROI does weakly reflect the underlying profitability. The internal rate of return derived from the cash recovery rate approach, however, seems to be more informative than the ROI.

Correlating Gene Expression Variation with cis-Regulatory Polymorphism in Saccharomyces cerevisiae

Identifying the nucleotides that cause gene expression variation is a critical step in dissecting the genetic basis of complex traits. Here, we focus on polymorphisms that are predicted to alter transcription factor binding sites (TFBSs) in the yeast, Saccharomyces cerevisiae. We assembled a confident set of transcription factor motifs using recent protein binding microarray and ChIP-chip data and used our collection of motifs to predict a comprehensive set of TFBSs across the S. cerevisiae genome. We used a population genomics analysis to show that our predictions are accurate and significantly improve on our previous annotation. Although predicting gene expression from sequence is thought to be difficult in general, we identified a subset of genes for which changes in predicted TFBSs correlate well with expression divergence between yeast strains. Our analysis thus demonstrates both the accuracy of our new TFBS predictions and the feasibility of using simple models of gene regulation to causally link differences in gene expression to variation at individual nucleotides.

Spectacle: fast chromatin state annotation using spectral learning

Epigenomic data from ENCODE can be used to associate specific combinations of chromatin marks with regulatory elements in the human genome. Hidden Markov models and the expectation-maximization (EM) algorithm are often used to analyze epigenomic data. However, the EM algorithm can have overfitting problems in data sets where the chromatin states show high class-imbalance and it is often slow to converge. Here we use spectral learning instead of EM and find that our software Spectacle overcame these problems. Furthermore, Spectacle is able to find enhancer subtypes not found by ChromHMM but strongly enriched in GWAS SNPs. Spectacle is available at https://github.com/jiminsong/Spectacle.

Variation in piRNA and transposable element content in strains of Drosophila melanogaster

Transposable elements (TEs) are one of the most important features of genome architecture, so their evolution and relationship with host defense mechanisms have been topics of intense study, especially in model systems such as Drosophila melanogaster. Recently, a novel small RNA-based defense mechanism in animals called the Piwi-interacting RNA (piRNA) pathway was discovered to form an adaptive defense mechanism against TEs. To investigate the relationship between piRNA and TE content between strains of a species, we sequenced piRNAs from 16 inbred lines of D. melanogaster from the Drosophila Genetic Reference Panel. Instead of a global correlation of piRNA expression and TE content, we found evidence for a host response through de novo piRNA production from novel TE insertions. Although approximately 20% of novel TE insertions induced de novo piRNA production, the abundance of de novo piRNAs was low and did not markedly affect the global pool of ovarian piRNAs. Our results provide new insights into the evolution of TEs and the piRNA system in an important model organism.