1,600 research outputs found

    An approach to executive training

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    Thesis (M.B.A.)--Boston Universit

    The Forgotten Ones: Maternal Abusers and their Victims: a Pilot Study

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    This paper analyses the phenomenon of mothers who sexually abuse their children, most specifically their sons. It defines the term Maternal Abuse, offers a review of the contemporary academic discourse on female sexual abusers, and presents a quantitative study of maternal abuse in the Republic of Ireland and Northern Ireland, which appears to show that the existing statistics from Health Board and ISPCC reports (SEHB Section 8 Report, 1997; ISPCC National Report, 1997) significantly underestimate it\u27s prevelence. It concludes by suggesting that though Ireland is considerably more aware of the phenomenon of sexual abuse than in the past, but that the incidence of this particular type of abuse is poorly recognised by the child protection and welfare authoritie

    Xenopus Drf1, a Regulator of Cdc7, Displays Checkpoint-dependent Accumulation on Chromatin during an S-phase Arrest

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    We have cloned a Xenopus Dbf4-related factor named Drf1 and characterized this protein by using Xenopus egg extracts. Drf1 forms an active complex with the kinase Cdc7. However, most of the Cdc7 in egg extracts is not associated with Drf1, which raises the possibility that some or all of the remaining Cdc7 is bound to another Dbf4-related protein. Immunodepletion of Drf1 does not prevent DNA replication in egg extracts. Consistent with this observation, Cdc45 can still associate with chromatin in Drf1-depleted extracts, albeit at significantly reduced levels. Nonetheless, Drf1 displays highly regulated binding to replicating chromatin. Treatment of egg extracts with aphidicolin results in a substantial accumulation of Drf1 on chromatin. This accumulation is blocked by addition of caffeine and by immunodepletion of either ATR or Claspin. These observations suggest that the increased binding of Drf1 to aphidicolin-treated chromatin is an active process that is mediated by a caffeine-sensitive checkpoint pathway containing ATR and Claspin. Abrogation of this pathway also leads to a large increase in the binding of Cdc45 to chromatin. This increase is substantially reduced in the absence of Drf1, which suggests that regulation of Drf1 might be involved in the suppression of Cdc45 loading during replication arrest. We also provide evidence that elimination of this checkpoint causes resumed initiation of DNA replication in both Xenopus tissue culture cells and egg extracts. Taken together, these observations argue that Drf1 is regulated by an intra-S-phase checkpoint mechanism that down-regulates the loading of Cdc45 onto chromatin containing DNA replication blocks

    Roles of replication fork-interacting and Chk1-activating domains from claspin in a DNA replication checkpoint response

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    Claspin is essential for the ATR-dependent activation of Chk1 in Xenopus egg extracts containing incompletely replicated DNA. Claspin associates with replication forks upon origin unwinding. We show that Claspin contains a replication fork-interacting domain (RFID, residues 265–605) that associates with Cdc45, DNA polymerase ε, replication protein A, and two replication factor C complexes on chromatin. The RFID contains two basic patches (BP1 and BP2) at amino acids 265–331 and 470–600, respectively. Deletion of either BP1 or BP2 compromises optimal binding of Claspin to chromatin. Absence of BP1 has no effect on the ability of Claspin to mediate activation of Chk1. By contrast, removal of BP2 causes a large reduction in the Chk1-activating potency of Claspin. We also find that Claspin contains a small Chk1-activating domain (residues 776–905) that does not bind stably to chromatin, but it is fully effective at high concentrations for mediating activation of Chk1. These results indicate that stable retention of Claspin on chromatin is not necessary for activation of Chk1. Instead, our findings suggest that only transient interaction of Claspin with replication forks potentiates its Chk1-activating function. Another implication of this work is that stable binding of Claspin to chromatin may play a role in other functions besides the activation of Chk1

    Governance of environmental risk: New approaches to managing stakeholder involvement

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    Disputes concerning industrial legacies such as the disposal of toxic wastes illustrate changing pressures on corporations and governments. Business and governments are now confronted with managing the expectations of a society increasingly aware of the social and environmental impacts and risks associated with economic development and demanding more equitable distribution and democratic management of such risks. The closed managerialist decision-making of the powerful bureaucracies and corporations of the industrial era is informed by traditional management theory which cannot provide a framework for the adequate governance of these risks. Recent socio-political theories have conceptualised some key themes that must be addressed in a more fitting approach to governance. We identify more recent management and governance theory which addresses these themes and develop a process-based approach to governance of environmental disputes that allows for the evolving nature of stakeholder relations in a highly complex multiple stakeholder arena. © 2008 Elsevier Ltd. All rights reserved

    Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

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    INTRODUCTION Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.This work was supported by grants from the US Army Medical Research and Materiel Command (W81XWH0410385 to KAD and DAMD17-01-1-0315 to ACB) and the National Institutes of Health (RO1-CA095164 to DJJ)

    Stormwater sand filters in water-sensitive urban design

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    This paper investigates the suitability of sand filters for harvesting and treating stormwater for non-potable reuse purposes. A stormwater sand filtration device was constructed in a small urban catchment in Sydney, Australia. A sand filter is typically used in water-sensitive urban design (WSUD) as a component of a treatment train to remove pollution from stormwater before discharge to receiving waters, to groundwater or for collection and reuse. This paper describes an 18 month field study undertaken to determine the effectiveness and pollutant removal efficiency of a sand filter, and the differences in the pollutant removal efficiency of two grades of sand. A comparison of pollutant removal with previous literature on sand filters showed similar efficiencies but nutrient removal was higher than expected. A further unexpected result was that the coarse filter media performed as well as the fine media for most pollutant types and was superior in suspended solids removal. Improved modelling equations for predicting suspended solids and total phosphorus removal in sand filters are also presented in this paper

    Spectroscopy and Imaging Performance of the Liquid Xenon Gamma-Ray Imaging Telescope (LXeGRIT)

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    LXeGRIT is a balloon-borne Compton telescope based on a liquid xenon time projection chamber (LXeTPC) for imaging cosmic \g-rays in the energy band of 0.2-20 MeV. The detector, with 400 cm2^2 area and 7 cm drift gap, is filled with high purity LXe. Both ionization and scintillation light signals are detected to measure the energy deposits and the three spatial coordinates of individual \g -ray interactions within the sensitive volume. The TPC has been characterized with repeated measurements of its spectral and Compton imaging response to \g -rays from radioactive sources such as \na, \cs, \yt and Am-Be. The detector shows a linear response to \g -rays in the energy range 511 keV -4.4 MeV, with an energy resolution (FWHM) of \Delta E/E=8.8% \: \sqrt{1\MeV /E}. Compton imaging of \yt \g -ray events with two detected interactions is consistent with an angular resolution of ∼\sim 3 degrees (RMS) at 1.8 MeV.Comment: To appear in: Hard X-Ray, Gamma-Ray and Neutron Detector Physics XI, 2000; Proc. SPIE, vol. 4140; K.A. Flanagan & O.H. Siegmund, ed
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