The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control

The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.

Genetic variations in colorectal cancer risk and clinical outcome

Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of “missing heritability” in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the “missing heritability” still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.

Grid Voltage Sensor-less Protection Scheme for One Cycle-Controlled Single-phase Photovoltaic Inverter Systems

One-cycle-controlled(OCC)inverters are suitable for small single-phase photovoltaic distributed-generator systems because of their simplicity,phase-locked-loop free structure,grid voltage sensor-less operation,and cost-effectiveness.Grid voltage sensor-less control helps reduce cost and increases reliability in operation.However various sensors are used for implementation of a protection mechanism.In this paper,a grid voltage sensorless protection scheme for OCC based single-phase inverter systems is proposed.The estimated value of voltage at point of common coupling(VPCC)is used for protecting the system during over/under voltage conditions of the grid,implementing of voltage ride through conditions,and for disconnecting the grid during islanded conditions.The VPCC is estimated from the measured inverter current,switching pulses,and the measured dc-link voltage using a second-order filter.Simulation and experimental studies are performed to verify the efficacy of the proposed voltage sensor-less protection mechanism triggered using estimated VPCC.

A composite controller for grid connected photovoltaic systems

This paper addresses a new composite controller for a boost-buck inverter to interface the photovoltaic array with the power grid. Based on dynamically tracking the maximum power point, two novel control methodologies are proposed to control the DC-bus and the output current for the inverter. First, a new linear cycle discrete control algorithm is introduced to realize linear control of the DC-bus voltage and synchronously get the reference current for the inner current loop with a little calculation. Then, to assure a good adaptability to noise and model uncertainty, an auto-disturbance rejection controller is chosen as the output current controller, which does not depend on precise mathematics model. Thus, output current of PV system to the grid is with low harmonic distortion and unity power factor. Simulations and experiments are performed, and the results show that the system is of excellent robustness and effective.

High-Speed EMU TCMS Design and LCC Technology Research

This paper introduces the high-speed electrical multiple unit （EMO） life cycle, including the design, manufacturing, testing, and maintenance stages. It also presents the train control and monitoring system （TCMS） software development platform, the TCMS testing and verification bench, the EMU driving simulation platform, and the EMU remote data transmittal and maintenance platform. All these platforms and benches combined together make up the EMU life cycle cost （LCC） system. Each platform facilitates EMU LCC management and is an important part of the system.

Activation of hypothalamic gono-like neurons in female rats during estrus

In mammals, gonadal function is controlled by the activity of hypothalamic gonadotropin-releasing hormone neurons, which control the secretion of adenohypophyseal and gonadal hormones. However, there are a number of unanswered questions in relation to gonadal function. It is currently unknown how erotogenic stimulation of the genitals influences the subpopulation of hypothalamic medial preoptic area neurons, antidromically identified as projecting to the median eminence at different periods of the estrous cycle. Additionally, the distinctiveness of hypothalamic medial preoptic area neurons, with respect to methods of feedback control by exogenous hormones, is also unknown. In this study, spontaneous discharges from individual neurons encountered within the medial preoptic area, gono-like neurons, were recorded extracellularly using glass microelectrodes. To confirm the cellular and histochemical properties of the recording units, antidromic stimulation was performed using a side-by-side bipolar stimulating electrode placed into the median eminence, alongside microiontophoretic injections of the conventional tracer, horseradish peroxidase. In addition, further immunohistochemical analyses were performed. Results showed that elevated gono-neuron activity was accompanied by increased background activity and greater responses to erotogenic stimuli during estrus. Application of clitoral traction stimulation resulted in increased activation of the gono-like neurons. This neuronal activity was noticeably inhibited by β-estradiol administration. Immunohistochemical analyses revealed the presence of gonadotropin-releasing hormone-reactive protein in hypothalamic cells in which electrophysiological recordings were taken. Thus, medial preoptic area neurons represent the subset of hypothalamic gonadotropin-releasing hormone neurons described from brain slices in vitro, and might serve as a useful physiological model to form the basis of future in vivo studies.

Plasma Feedback Control System for HL-2A Tokamak

As the limit of time and budget etc, the control system of HL-2A just could be operated in programmed discharge when HL-2A was checked and accepted in 2002. Recent years, many subsystem of HL-2A have been improved in functions and performances. And the demand for experiment of HL-2A is becoming more and more higher in plasma discharge parameters. So it＇s necessary to develop a plasma feedback control system （ FBCS ） which has enough functions and good stability and reliability to satisfy the demand of experiment on HL-2A.

Human DNA oncogenic viruses and their transforming protein interactions with cell cycle control proteins

Purpose Both oncogenic viruses and cell cycle control proteins are fast growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfere with cell cycle pathways. To understand the mechanisms by which viral proteins regulate apoptosis and target the cellular pathways may lead to the development of new remedies for some cancers.Data sources English literature searched by MEDLINE from January 1995 to August 1998.Study selection and data extraction More than one hundred research papers published in these areas over the past three years. Only new and important breakthroughs in these papers are selected. The review focuses on DNA viruses associated with the development of human cancers.Results and conclusions Some DNA viruses contain oncogenic proteins which transform normal cells in vitro and induce tumors in animals. These viral proteins target the cellular pathways and block apoptosis induced by receptors or in response to signal transduction. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in regulation of these interactions.