Functional analyses of hTel2 and TRF2 deltaB: Insights Into the Role of a New DNA Damage Pathway and Homologous Recombination in Mammalian Telomere Function

Tel2 influences telomere length in S. cerevisiae and DNA-damage signaling in C. elegans. We found that endogenous human Tel2 (hTel2) localized in a diffuse, granular patter to the nuclei of human cells where it was enriched in PML nuclear bodies, but telomeres. Surprisingly, hTel2 also localized to centrosomes. Although hTe!2 did not detectably interact with telomeric proteins or telomeric chromatin, the overexpression untagged hTel2 resulted in the slow elongation of telomeres in HTC75 and SK-HEP-1 cells. Furthermore, hTel2 overexpression suppressed the accumulation of cells in G2 after ionizing radiation. The depletion of hTel2 in HeLa cells by RNA interference resulted in apoptotic cell death. Furthermore, hTel2 depletion resulted in the accumulation of aberrant mitotic cells that possessed disorganized metaphase chromosomes. The metaphase chromosomes of hTel2 depleted cells were curly suggesting that hTel2 played a role in chromosome compaction. A role for hTel2 in establishing chromatin structure during S-phase could explain its multiple localizations and phenotypes. TRF2 protects telomeres from non-homologous end joining (NHEJ), possibly through the formation of a t-loop structure. A mutant allele of TRF2, TRF2AB, retained the ability to suppress NHEJ but induced dramatic deletions of telomeric DNA. This catastrophic telomere shortening was accompanied by a DNA damage response and senescence. Using FISH and CO-FISH, TRF2AB was found to induce rapid, stochastic deletions that preferentially affected leading strand telomeres (parental C-strand) DNA replication. Genetic analyses demonstrated that TRF2AB-induced deletions required Nbsl, a component of the Mrell complex, and XRCC3, a component of the RAD51C/XRCC3 Holliday junction (HJ) resolvase, suggesting the involvement of homologous recombation (HR) in the deletions. Consistent with a role for HR, TRF2AB induced the formation of t-loop-sized telomeric circles. These telomeric circles were detected in unperturbed cells suggesting that t-loop deletion by H R could explain the stochastic nature of telomere shortening and senescence in somatic cells. Furthermore, telomerase-negative ALT cells had abundant telomeric circles, suggesting that recombination-mediated elongation of ALT telomeres could involve telomeric circles. These findings show that TRF2 regulates both NHEJ and HR at mammalian telomeres and that HR at telomeres influences the integrity and dynamics of mammalian telomeres

Effect of rollover risk on default risk: evidence from bank financing

We study the effect of rollover risk on the risk of default using a comprehensive database of U.S. industrial firms during 1986–2013. Dependence on bank financing is the key driver of the impact of rollover risk on default risk. Default risk and rollover risk present a significant positive relation in firms dependent on bank financing. In contrast, rollover risk is uncorrelated with default probability in the case of firms that do not rely on bank financing. Our measure of rollover risk is the amount of long-term debt maturing in one year, weighted by total assets. In the case of a firm that depends on bank financing, an increase of one standard deviation in this measure leads to a significant increase of 3.2% in its default probability within one year. Other drivers affecting the interaction between rollover risk and default risk are whether a firm suffers from declining profitability and has poor credit. Additionally, rollover risk's impact on default probability is stronger during periods when credit market conditions are tighter

Heartthrob in Cyberspace - The Characteristics of the Popular Online Daters

Online dating websites are currently popular application for Internet users to make new friends and find their partners. An interesting observation is that some people are more popular than others in online dating websites. The current study focus on the personal profile characteristics which make one a popular dater. By two field surveys, this study discusses the relationship between online daters\u27 personal profiles and their popularity

Normative Legitimacy in the Commercialization of Online Community Website

Many online community websites start their operation by a not-for-profit business model, which attracts a lot of users to engage in. The huge user base and heavy Internet traffic could generate revenue and wealth for the websites. When the online communities are becoming popular, entrepreneurs of the online community website may hope to commercialize the online community. Nevertheless, some of community participants are against the commercialization of the online community website, since they regard that the property of online community is belonged to users rather than website owners. Users may challenge the legitimacy in the commercialization process of online community, and argue that the online community should be owned by the public rather than by a company since the enormous community participants put effort in it and make the website a popular one. This study used two case studies of online communities to explain the normative legitimate issues in the entrepreneurship of online community

A WAVELET-BASED VARIABLE CONTROL PROCEDURE FOR DETECTING PROCESS MEAN SHIFT

This paper develops a wavelet-based approach for a variable control chart, and adopts the data decomposition and linear combination techniques to detect process shifts. The Shewhart, exponentially weighted moving average (EWMA), and cumulative sum (CUSUM) control charts are the most popular monitoring process graph tools. However, these charts were developed for different process situations. If a user chooses an inappropriate control chart to monitor a process, the correct control result will not be obtained. This study used the wavelet transform to develop a novel variable control procedure. First, the Haar function was used as the basis for data decomposition. Next, the linear combination technique was used to combine different resolution data through wavelet transform decomposition. Simulations were adopted to evaluate performance. An analysis showed that the detection ability of the wavelet-based variable control chart was superior to the EWMA control chart in a comparison of average run length (ARL) results

Valuation of Exit Strategy under Decaying Abandonment Value

We examine the valuation of abandonment decision in a contingent claims model with uncertainty in future market conditions and analyze the effect of determinants on the abandonment value. We find the abandonment value is positively related with the number of abandonment opportunities. The increase in the volatility, variable cost, and facility value increases the expected abandonment value, whereas the increase in the growth rate and depreciation rate reduces the expected abandonment value. The volatility, growth rate, and depreciation rate are negatively related with the exit threshold, whereas the variable cost and facility value are positively related with the exit threshold