Investigations into the mechanisms of telomere structure and function

2012 Spring.Includes bibliographical references.Telomere dysfunction is most commonly defined as critical shortening; i.e., loss of telomere sequence due to a variety of causes, usually the end-replication problem. However telomeres and their arsenal of associated proteins also provide essential end-capping structure that protects the ends of linear eukaryotic chromosomes. The overall goal of the studies presented here was to provide new insight into underlying mechanisms of telomeric structure and function. We examined the role of telomere function in Acute Myeloid Leukemia. We observed genomic instability in association with radiation-induced AML, and this association was observed following AML induction with both gamma (γ)- ray and 1 Gev 56Fe ion exposure. Furthermore, we observed a clonal fusion event involving telomeres in a human AML cell line. Taken together, our AML studies underline the importance of genome stability and its link to carcinogenesis. We previously reported a role for the DNA damage repair protein DNA-PKcs in mammalian telomere end-capping function, where inappropriate telomere fusions, as well as telomere fusions to other broken DNA ends, were observed in DNA-PKcs deficient backgrounds. DNA-PKcs has many proposed phosphorylation substrates, one of the most intriguing and relevant being the recently identified heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), an RNA binding protein that associates with telomeres. It is also now well accepted that telomeres are transcribed into telomeric repeat-containing RNAs, or TERRA, which are thought to contribute to telomeric chromatin structure. Taken together, we hypothesized that DNA-PKcs mediated phosphorylation of hnRNA1 plays an important role in tethering TERRA to telomere ends, thereby possibly contributing to telomere chromatin structure and function. Our data suggests that TERRA localization at telomeres is independent of hnRNP A1 and DNA-PKcs kinase activity. Rather, we observed decreased TERRA levels following DNA-PKcs kinase inhibition, suggesting DNA-PKcs indirectly regulates TERRA levels. Depletion of hnRNP A1 did not influence TERRA levels, but resulted in elevated frequencies of what have previously been termed "fragile" telomeres and telomere sister chromatid exchange (T-SCE), both indicative of a role for hnRNP A1 in facilitating telomere replication

Langmuir-Maxwell and Langmuir-Smoluchowski boundary conditions for thermal gas flow simulations in hypersonic aerodynamics

The simulation of nonequilibrium thermal gas flow is important for the aerothermodynamic design of re-entry and other high-altitude vehicles. In computational fluid dynamics, the accuracy of the solution to the Navier–Stokes–Fourier (N–S–F) equations depends on the accuracy of the surface boundary conditions. We propose new boundary conditions (called the Langmuir–Maxwell and the Langmuir–Smoluchowski conditions), for use with the N–S–F equations, which combine the Langmuir surface adsorption isotherm with the Maxwell/Smoluchowski slip/jump conditions in order to capture some of the physical processes involved in gas flow over a surface. These new conditions are validated for flat plate flow, circular cylinder in cross-flow, and the flow over a sharp wedge for Mach numbers ranging from 6 to 24, and for argon and nitrogen as the working gases. Our simulation results show that the new boundary conditions give better predictions for the surface pressures, compared with published experimental and DSMC data

The impact of personality traits on the ethical leadership, job performance and job satisfaction of public servants – A case study of the Northern public sector of Vietnam

The study aims to explore the impact of personality traits on ethical leadership, job performance and job satisfaction of public servants working in the Northern public sector of Vietnam. A quantitative approach was employed to evaluate the impact of personality traits on ethical leadership, job performance, and job satisfaction. A structured questionnaire was administered to obtain information from public servants. The SPSS 26 was used to conduct the demographic information of public servants and the SmartPLS 3.0 version was used to process the SEM. The research results showed Big Five personality traits have a positive impact on ethical leadership, job performance, and job satisfaction. Additionally, ethical leadership and job performance have a positive correlation with the job satisfaction of public servants. The research results were used to recommend leaders of State Administrative agencies in the Red River Delta to understand the personality traits of public servants to increase job satisfaction and achieve greater job performance

Small Ethnic Restaurant Business Owner Strategies to Remain Operable Beyond 7 Years

The failure rate among small businesses is high. More than half of all small businesses fail within the first 7 years of operation. The purpose of this multi-case study was to explore the strategies that successful small ethnic restaurant owners employed to remain operable beyond 7 years. Three successful ethnic restaurant owners who have been operating their restaurant for at least 7 years in Greater Vancouver, British Columbia, Canada were selected. Data were gathered from participant interviews and from an examination of available physical artifacts such as the locations, premises, websites, and social media pages. The resource-based view by Edith Penrose was the underlying conceptual framework for this research. Within-method triangulation was used to ensure the rigorousness of the study. In the study, 5 themes were identified: hard work, interest or passion, family support, location, and food and service quality. These findings underscore the importance of hard work, business interest, family support, prime location, and quality food for successful small businesses. Current and future small ethnic restaurant business owners may apply these findings to improve their business performance and survival rate

Modelling of calibration steam flowmeter test bench

The present project develops simulation methods for the test bench that serves to calibrate the steam flowmeters by using steam as working fluid. The test bench contains a condenser, the purpose of which is to condense the steam. By maintaining a steady-state regime, the weight of condensate measured during a given period of the time is used to calibrate the steam flowmeter. Two mathematical models are developed in this project for the heat transfer process within the condenser, which is a shell-and-tube heat exchanger. The first model is based on neural network theory for predicting steam temperature, pressure, flow and the height of condensate. The input parameters to this model include the opened-closed position of the control valves and the inlet temperature of the cooling water. The second model (physical model) is based on the mass and energy conservation principles. For increasing the accuracy, the condenser is divided into control volumes to which the mass and energy balances are applied. The model describes the dynamic response of the system at different locations including the condensate level and the steam pressure within the heat exchanger. The input values are the opened-closed position of the valves, the flow rate and inlet temperature of cooling water. Both of these models give satisfactory results compared with experimental data. However, the physical model is preferred by its capability of explaining the relationships between parameters. It is suggested for a future work that physical model is applied to a multivariable control system for the regulation of the level of condensate and the steam pressure

Biomolecular evaluation of three contrasting rice cultivars (Oryza sativa L.) in salt stress response at seedling stage.

Salt contamination of soils due to climate change faces a severe environmental issue that affects crop production today. However, the response mechanism in plants to salt stress is not fully understood. The present study investigated molecular and biochemical changes under salt stress in rice seedlings of three rice cultivars, i.e., AGPPS114 (salt-tolerant), OM6967 (moderately tolerance), VD20 (salt-sensitive). Increasing salt concentration leads to a reduction in shoot/root length but different levels among the cultivars. In contrast, reactive oxygen species (ROS) accumulation and lipid peroxidation increased progressively with increasing salt concentration and time course treatment. However, at 250 ?M of NaCl, these parameters were more adversely affected in VD20 than AGPPS114 and OM6967. Using ICP showed that Na+ accumulation in rice root increased gradually with increasing NaCl concentrations in all cultivars under salt treatment but was low in salt-sensitive cultivar VD20 compared to other cultivars. Antioxidant enzyme activity analysis indicated catalase (CAT) and superoxide dismutase (SOD) were induced during salt treatment in all cultivars. The results also showed greater proline and glycine betaine accumulation in the AGPPS114 than OM6976 and VD20. qPCR indicated a significant difference in transcript levels of the Na+-transporter gene OsSOS1, OsNHX1 and OsHKT1s in AGPPS114 and OM6967 cultivars compared to VD20 cultivar. In summary, the active regulation of genes related to Na+ transport at the transcription level and with high glycine betaine and proline accumulation levels may be involved in salt tolerance mechanisms and thus might be useful for selecting tolerant plants

On a system of nonlinear wave equations with the Kirchhoff-Carrier and Balakrishnan-Taylor terms

summary:We study a system of nonlinear wave equations of the Kirchhoff-Carrier type containing a variant of the Balakrishnan-Taylor damping in nonlinear terms. By the linearization method together with the Faedo-Galerkin method, we prove the local existence and uniqueness of a weak solution. On the other hand, by constructing a suitable Lyapunov functional, a sufficient condition is also established to obtain the exponential decay of weak solutions

Preparation and characterization of magnesium hydroxyapatite coatings on 316L stainless steel

Magnesium hydroxyapatite coatings (MgHAp) were deposited on the surface of 316L stainless steel (316L SS) substrates by electrodeposition technique. Different concentrations of Mg2+ ion were incorporated into the apatite structure by adding Mg(NO3)2 into electrolyte solution containing 3×10-2 M Ca(NO3)2, 1.8×10-2 M NH4H2PO4 and   6×10-2 M NaNO3. With Mg2+ concentration 1×10-3 M, the obtained coatings have 0.2 wt% Mg2+. The influences of scanning potential ranges, scanning times to deposit MgHAp coatings were researched. The analytical results FTIR, SEM, X-ray, EDX, thickness and adhension strength showed that MgHAp coatings were single phase of HAp, fibrous shapes, thickness 8.1 µm and adhesion strength 7.20 MPa at the scanning potential ranges of 0÷-1.7 V/SCE and scanning times of 5 scans. Keywords. 316L SS, Electrodeposition, MgHAp

Multiple-Symbol Differential Detection for Spatial Modulation

Approximately 3 dB Signal-to-Noise Ratio (SNR) loss is always paid with conventional Differential Spatial Modulation (DSM) as compared to coherent Spatial Modulation (SM). In this paper, a Multiple-Symbol Differential Detection (MSDD) technique is proposed for DSM systems to mitigate the loss due to differential detection. The new scheme can greatly narrow the 3 dB performance gap by extending the observation interval for differential decoding. The technique uses maximum-likelihood sequence detection instead of traditional symbol-by-symbol detection, and is carried out on the slow, flat Rayleigh fading channel. A generalized decision metric is derived for an observation interval of arbitrary length. It is shown that for a moderate number of symbols, MSDD provides approximately 1.5 dB performance improvement over the conventional differential detection. In addition, a closed-form pairwise error probability and approximate bit error probability (BEP) are derived for multiple-symbol differential spatial modulation. Results show that the theoretical BEP matches well the simulated one. The BEP is shown to converge asymptotically with the number of symbols in the observation interval to that of the differential scheme with coherent detection

New temperature jump boundary condition in high-speed rarefied gas flow simulations

The effect of the sliding friction has been important in calculating the heat flux of gas flow from the surface since there is some slip over the surface. There has not been any the temperature jump condition including the sliding friction part so far. In this paper, we will propose a new temperature jump condition that includes the sliding friction. Our new temperature jump condition will be evaluated for NACA0012 micro-airfoil in high-speed rarefied gas flow simulations using the CFD method, which solves the Navier-Stokes equations within the OpenFOAM framework with working gas as air. The airfoil case is simulated with various Knudsen numbers from 0.026 to 0.26, and the angles-of-attack (AOAs) from 0-deg to 20-deg. The surface gas temperatures predicting by our new temperature jump condition give good agreements with the DSMC data, especially the NACA0012 micro-airfoil cases with the high Knudsen numbers, Kn = 0.1, and Kn = 0.26 with AOA = 20-deg. for the lower surface