Functions of DNA Damage Response Factors in Lymphocyte Development and Transformation

DNA double strand breaks (DSBs) can activate cell cycle checkpoints or apoptosis, and lead to genomic alterations that drive malignant transformation. The H2AX core histone variant is phosphorylated in chromatin around DSBs by kinases such as ATM and DNA-PKcs. However, how H2AX suppresses chromosome breaks and translocations in cells and prevents tumorigenesis in mice and humans is not well understood. V(D)J recombination is a genetically programmed DNA damage and repair process that assembles the variable region exons of antigen receptor genes in developing lymphocytes. Using an inducible V(D)J recombination system, I found that H2AX is phosphorylated along cleaved antigen receptor loci DNA strands, prevents their irreversible separation in G1 phase, and reduces chromosome breaks and translocations in subsequent cell cycles. Consistent with H2AX functions in DSB repair, I also demonstrated that conditional H2AX deletion results in accumulation of genomic instability in cells, but delays tumor onset in a mouse thymic lymphoma model, presumably due to increased death of cells with synthetic loss of multiple repair factors. To further test this possibility, I generated cells and mice deficient in both H2AX and ATM to examine whether ATM-independent H2AX functions downstream of other kinases are essential for proper DSB repair. I found that thymocyte-specific ablation of H2AX in ATM-deficient mice results in a 50% reduction in thymus cellularity but does not accelerate or delay tumorigenesis. My results suggest that the outcomes of functional interactions between DNA damage response factors likely depend on the cellular context. Additionally, I discovered a novel function of ATM in regulating mono-allelic recombination at the immunoglobulin light chain locus. ATM could orchestrate the signaling pathways enforcing allelic exclusion to provide a time window to test whether the rearrangement on the first allele is productive. In summary, my work has provided novel mechanistic insights into how DNA damage and repair factors coordinately regulate V(D)J recombination, lymphocyte development and neoplastic transformation

Corporate credit risk prediction under stochastic volatility and jumps

This paper examines the impact of allowing for stochastic volatility and jumps (SVJ) in a structural model on corporate credit risk prediction. The results from a simulation study verify the better performance of the SVJ model compared with the commonly used Merton model, and three sources are provided to explain the superiority. The empirical analysis on two real samples further ascertains the importance of recognizing the stochastic volatility and jumps by showing that the SVJ model decreases bias in spread prediction from the Merton model, and better explains the time variation in actual CDS spreads. The improvements are found particularly apparent in small firms or when the market is turbulent such as the recent financial crisis

RNACompress: Grammar-based compression and informational complexity measurement of RNA secondary structure

<p>Abstract</p> <p>Background</p> <p>With the rapid emergence of RNA databases and newly identified non-coding RNAs, an efficient compression algorithm for RNA sequence and structural information is needed for the storage and analysis of such data. Although several algorithms for compressing DNA sequences have been proposed, none of them are suitable for the compression of RNA sequences with their secondary structures simultaneously. This kind of compression not only facilitates the maintenance of RNA data, but also supplies a novel way to measure the informational complexity of RNA structural data, raising the possibility of studying the relationship between the functional activities of RNA structures and their complexities, as well as various structural properties of RNA based on compression.</p> <p>Results</p> <p><it>RNACompress </it>employs an efficient grammar-based model to compress RNA sequences and their secondary structures. The main goals of this algorithm are two fold: (1) present a robust and effective way for RNA structural data compression; (2) design a suitable model to represent RNA secondary structure as well as derive the informational complexity of the structural data based on compression. Our extensive tests have shown that <it>RNACompress </it>achieves a universally better compression ratio compared with other sequence-specific or common text-specific compression algorithms, such as <it>Gencompress, winrar </it>and <it>gzip</it>. Moreover, a test of the activities of distinct GTP-binding RNAs (aptamers) compared with their structural complexity shows that our defined informational complexity can be used to describe how complexity varies with activity. These results lead to an objective means of comparing the functional properties of heteropolymers from the information perspective.</p> <p>Conclusion</p> <p>A universal algorithm for the compression of RNA secondary structure as well as the evaluation of its informational complexity is discussed in this paper. We have developed <it>RNACompress</it>, as a useful tool for academic users. Extensive tests have shown that <it>RNACompress </it>is a universally efficient algorithm for the compression of RNA sequences with their secondary structures. <it>RNACompress </it>also serves as a good measurement of the informational complexity of RNA secondary structure, which can be used to study the functional activities of RNA molecules.</p

Luminescence of delafossite-type CuAlO2 fibers with Eu substitution for Al cations

CuAlO2 has been examined as a potential luminescent material by substituting Eu for Al cations in the delafossite structure. CuAlO2:Eu3+ nanofibers have been prepared via electrospinning for the ease of mitigating synthesis requirements and for future optoelectronics and emerging applications. Single-phase CuAlO2 fibers could be obtained at a temperature of 1100 °C in air. The Eu was successfully doped in the delafossite structure and two strong emission bands at ~405 and 610 nm were observed in the photoluminescence spectra. These bands are due to the intrinsic near-band-edge transition of CuAlO2 and the f-f transition of the Eu3+ activator, respectively. Further electrical characterization indicated that these fibers exhibit semiconducting behavior and the introduction of Eu could act as band-edge modifiers, thus changing the thermal activation energies. In light of this study, CuAlO2:Eu3+ fibers with both strong photoluminescence and p-type conductivity could be produced by tailoring the rare earth doping concentrations

An Asymmetric Hysteresis Model and Parameter Identification Method for Piezoelectric Actuator

Hysteresis behaviour degrades the positioning accuracy of PZT actuator for ultrahigh-precision positioning applications. In this paper, a corrected hysteresis model based on Bouc-Wen model for modelling the asymmetric hysteresis behaviour of PZT actuator is established by introducing an input bias φ and an asymmetric factor ΔΦ into the standard Bouc-Wen hysteresis model. A modified particle swarm optimization (MPSO) algorithm is established and realized to identify and optimize the model parameters. Feasibility and effectiveness of MPSO are proved by experiment and numerical simulation. The research results show that the corrected hysteresis model can represent the asymmetric hysteresis behaviour of the PZT actuator more accurately than the noncorrected hysteresis model based on the Bouc-Wen model. The MPSO parameter identification method can effectively identify the parameters of the corrected and noncorrected hysteresis models. Some cases demonstrate the corrected hysteresis model and the MPSO parameter identification method can be used to model smart materials and structure systems with the asymmetric hysteresis behaviour

A partially block randomized extended Kaczmarz method for solving large overdetermined inconsistent linear systems

This paper presents a partial block randomized extended Kaczmarz (PBREK) method for solving large overdetermined inconsistent linear system of equations $Ax = b$. The convergence theorem of the PBREK method is derived. Several examples are given to illustrate the effectiveness of the proposed PBREK method compared with the prevuious PREK method and the randomized extended Kaczmarz (REK) method