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Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from consumer products. Given the sensitivity of the developing organism to hormones, exposure of fetuses and infants is a concern. Here, CD-1 mice were exposed to environmentally relevant doses of BPA during gestation and the lactational period (gestational day 8 through postnatal day 16). At 3, 9 and 12–15 months of age, mammary glands from exposed offspring were examined for structural changes. BPA-exposed females demonstrated altered mammary phenotypes including the appearance of alveolar buds. Additionally, intraductal hyperplasias were observed exclusively in BPA–exposed females. These lesions had the appearance of "beaded" ducts, with epithelial cells present inside the ductal lumen and increased proliferation indexes compared to normal ducts. Similar structures have also been observed following exposure to other estrogens. These results are further evidence that perinatal BPA exposure can alter the morphology of the rodent mammary gland in adulthood.
Estrogens are involved in many aspects of female sexual development including organogenesis and maintenance of the reproductive tract and secondary sexual characteristics, as well as the regulation of the menstrual cycle, pregnancy and lactation. Estrogens also mediate cell proliferation in cells containing estrogen receptor (ER) and can bind to estrogen responsive elements to regulate the expression of select genes.
In humans, exposure to estrogens throughout life is the main known risk factor for breast cancer [1]. The positive correlation between increased intrauterine levels of estrogens observed in twin births and breast cancer in daughters born from such pregnancies also supports this link [2]. Additionally, women exposed therapeutically to the potent synthetic estrogen diethylstilbestrol (DES) while pregnant have a higher incidence of breast cancer [3]. Their daughters, so-called "DES daughters", are now reaching the age at which breast cancer is prevalent. A recent study reported that the incidence of breast cancer in DES daughters age 40 and older was significantly increased compared to unexposed women [4].
Bisphenol-A (BPA), a xenoestrogen used in the manufacturing of polycarbonate plastics and epoxy resins, has been shown to leach from food and beverage containers [5,6,7], and dental sealants and composites [8] under normal conditions of use [9]. BPA is a full agonist that binds both ERα and ERβ, although at lower affinities than estradiol [10,11]. Additional evidence suggests that BPA may be as potent as estradiol in mediating effects modulated via the membrane ER (reviewed in [12]). In 2005, a study conducted by the Centers for Disease Control and Prevention (CDC) examined 394 Americans and reported that BPA was found in 95% of urine samples [13] indicating that humans are routinely exposed to this chemical. A more recent CDC study of over 2500 Americans supports this finding with BPA detected in 92.6% of participants [14]. Urine concentrations ranged from 0.4–149 μg/L with a geometric mean of 2.6 μg/L and were significantly higher in children and adolescents compared to adults. Several studies have reported the presence of BPA in the serum of pregnant women, umbilical cord blood, amniotic fluid and fetal plasma [15,16,17,18,19]; these reports suggest that human fetuses are exposed to BPA during gestation. Additionally, BPA has been detected in human breast milk [20,21] indicating that exposure during lactation is also likely.
Because of its widespread presence in the environment and its estrogenic activity in vivo and in vitro [22,23,24,25], the potential for adverse effects of BPA exposure on human health is a concern. Exposure to xenoestrogens such as BPA during early development may have contributed to the increased incidence of infertility, genital tract abnormalities, and breast cancer observed in European and US human populations over the last 50 years [26,27,28]. In fact, exposure of rodents to low doses of BPA during perinatal development has been shown to induce early vaginal opening [29], advance the onset of puberty [30], disrupt estrous cyclicity [31,32] and decrease serum levels of luteinizing hormone following ovariectomy [32]. In female rodents, perinatal BPA exposure alters the development of estrogen-sensitive organs including the brain [33], vagina [34], ovaries [31,35], uterus [31,36], and the mammary gland [37,31,28,38,39].
Previous work in our laboratory has focused on the effects of perinatal exposure to BPA on mammary gland development (from gestational day 8 to postnatal day 2). Effects of BPA exposure were observed in morphological endpoints in the stromal and epithelial compartments as early as embryonic day (E)18 [38]. While normal pubertal mammary gland development is characterized by expansion of the epithelial tree into the surrounding stromal tissue, in utero exposure to BPA caused a decreased invasion of the stromal compartment, an increased number of the highly proliferative structures known as terminal end buds and an enhanced sensitivity to estradiol [28,39]. At 4 months of age, these animals had a significant increase in lateral branching, a phenomenon regulated by progesterone [28]. By 6 months of age, BPA-exposed animals demonstrated an overall increase in epithelial structures including terminal ducts and a premature appearance of alveolar buds, normally associated with pregnancy in the mouse [37]. Several of these changes suggest an increased risk of developing mammary cancer.
The effects of prolonged exposure to BPA through lactation have not yet been determined. ER is initially expressed in the developing mammary gland at E12.5 in the mesenchyme surrounding the epithelial bud [40] and at E18 is detected predominantly in the stroma with only punctate expression in the epithelium [38] suggesting that gestational BPA exposure is likely targeting ER in the mammary gland stroma. However, ER expression is mainly localized to the epithelium at postnatal time points [41]. Therefore, exposure during gestation and the lactation period during which the pups are reliant solely on maternal milk for their nutrition (through postnatal day 16) is likely to lead to phenotypes that are not predicted by gestational exposure alone.
We have now examined the effects of exposure to BPA from gestational day 8 through postnatal day 16 on the morphology of the adult mammary gland. At 3 months of age, we observed the appearance of alveolar buds in BPA-exposed animals, a structure that is normally associated with pregnancy in the mouse. Additionally, whole-mounted mammary glands from BPA-exposed females were examined for preneoplastic and neoplastic lesions at 3, 9, and 12–15 months of age. Intraductal hyperplasias were observed exclusively in the BPA-exposed females, and these lesions were characterized in greater detail.
Sexually mature CD-1 mice (Charles River, MA) were maintained in temperature and light controlled (14 hour light, 10 hour dark, lights on at 0400 h) conditions at the Tufts Medical Center Animal Facility in accordance with the Guide for Care and Use of Laboratory Animals. The cages and bedding were extracted using methods described previously [42]. Briefly, each item was incubated at 37°C for 1 hour with 100ml of HPLC grade methanol. The methanol was collected and dried down to completion with nitrogen gas and the residue was resuspended in sterile medium containing 5% charcoal-dextran-stripped (estrogen-free) fetal bovine serum. All tested negligible for estrogenicity using the E-SCREEN assay [42]. Food (Harlan Teklad 2018) was supplied ad libitum and was extracted using a method outlined in [42]. Briefly, the solid was homogenized and extracted with 10mM sodium acetate. These extracts were cleaned by methanol and n-hexane extraction followed by extraction with dichloromethane which was then passed through a Sep-Pak C-18 cartridge. Xenobiotics were then eluted from the column with n-hexane, dried down and resuspended as described above. Estrogenicity of feed was measured at ≤20 femtomoles of estrogen equivalents per gram, a negligible amount [42]. Water was supplied by glass bottles only.
Animals were allowed to adapt to the animal facility for several days before being placed together for mating. The morning on which a vaginal plug was detected was considered pregnancy day 1. On the evening of pregnancy day 8, dams were weighed and implanted subcutaneously with Alzet osmotic pumps (Alza Corp, Palo Alto, CA, model 2004) designed to deliver 50% dimethyl sulfoxide (DMSO; vehicle control) or BPA (Sigma) in 50% DMSO. These pumps continued to release at a constant rate (0.25 μl/hour) until day 16 of lactation. Exposure groups included: 0 (control), 0.25 (0.25BPA), 2.5 (2.5BPA), or 25 (25BPA) μg BPA / kg BW /day. Dams were allowed to deliver naturally and the litters were culled to 8 pups per mother on the day after birth. Litters were weaned on postnatal days 22–24.
At 3, 9, and 12–15 months of age, female offspring were killed; an incision was made along the skin at the ventral midline and the fourth inguinal mammary glands were dissected from the skin. One mammary gland was immediately immersed in phosphate buffered formalin overnight and prepared for paraffin sections using the methods described previously [28]. The second mammary gland was spread on a Superfrost positive charged glass slide (Fisher) and placed in phosphate buffered formalin overnight. Whole-mounted mammary glands were processed and stained with Carmine-alum using the methods described previously [28].
Digital images of whole-mount mammary glands were visualized using a Zeiss Stemi 2000-C dissection scope using a 2x objective and images were captured at 3900 dpi with a Zeiss AxioCam HRc digital camera (Carl Zeiss, Inc., Thornwood, NY). First, the entire whole-mounted mammary gland was examined and the number and location of ducts with a beaded appearance was recorded. Second, quantitative analyses of mammary gland dimensions were performed using the Zeiss AxioVision program version 4.4. For the morphometric analysis of mammary gland whole-mounts, one image was taken of each whole-mount in the area just anterior to the central lymph node. A total of 4–20 whole-mounts were examined for each treatment and timepoint (see Table 4). To analyze the percentage of tissue occupied by ducts, terminal ducts, and alveolar buds (including lobuloalveolar units), a 130-point grid was superimposed on each image and the structure at each crosshair was counted. The volume fraction of each structure was calculated as the number counted at crosshairs / 130 crosshairs × 100 as described previously [43]. For a randomly positioned point grid, the number of points hitting the phase of interest (i.e. ducts, alveolar buds, etc.) divided by the number hitting the whole field of view gives an unbiased estimate of volume fraction. The area of the phase of interest per unit area of the reference space is an excellent predictor of the volume of the phase of interest per unit volume [43].
In some whole-mounts, epithelial ducts were excised using a scalpel with the aid of a dissection scope. Some excised ducts were placed on Superfrost slides and mounted with permanent mounting medium and glass coverslips for confocal imaging. Other excised ducts were washed with xylene, infiltrated with paraffin under vacuum, and embedded in paraffin positioned parallel or perpendicular to the tissue mold cassettes. Longitudinal and cross-sections of the excised ducts were obtained.
Because the whole-mount excisions were stained with Carmine-alum, which autofluoresces, Z-series optical sections (0.98 μm) were collected on excised ducts using a Zeiss LSM510 Confocal microscope. Ducts were visualized using a HeNe laser with an excitation wavelength of 633 nm and a reflective (detected) wavelength of 650 nm. Images were collected using a Plan-Apochromat 20x objective.
Sections were treated with xylene to remove paraffin and rehydrated through a series of alcohols and distilled water. Sections were then stained with hematoxylin and eosin, PAS, von Kossa, or Masson's trichrome according to standard protocols. Samples were dehydrated and mounted with a permanent mounting medium (Sigma). Sections were viewed through a Zeiss Axioskop 2 plus light microscope at 10x and 40x. Images were captured at 3900 dpi using the AxioCam HRc digital camera.
Paraffin sections of whole mammary glands were treated with xylene, rehydrated, and then heated in 10 mM citrate buffer (pH 6) for antigen retrieval as described previously [28]. Antigen retrieval was not performed on sections of ducts excised from whole-mounts because of their fragility, thus requiring different concentrations of antibodies to achieve a positive signal (see Table 1). Blocking of non-specific binding and treatment with antibodies was performed as described previously [28]. Samples were counterstained with Harris' hematoxylin, dehydrated, and mounted with a permanent mounting medium. Sections were viewed through a Zeiss Axioskop 2 plus light microscope with 5x, 10x, 40x, and 100x objectives. Images were captured at 3900 dpi using the AxioCam HRc digital camera. To quantify Ki67, ERα and progesterone receptor (PR) expression in normal ducts, all epithelial cells in three arbitrarily chosen 40x fields were counted, with at least 200 cells assessed for each animal. For each antibody, 4–6 animals were examined per treatment. To calculate the proliferation index of epithelial ducts, the number of Ki67 positive cells was divided by the total number of cells counted.
The SPSS statistical software package 15.0 (SPSS Inc., Chicago, IL) was used for all statistical analyses. ANOVA followed by Bonferroni posthoc tests were used to assess differences between treatment groups for each exposure paradigm. A Chi Square test was performed to compare the incidence of beaded ducts in the mammary gland epithelium of control and BPA-exposed animals. To account for litter effects, one animal was randomly selected from each litter for each endpoint. For all statistical tests, results were considered significant at p < 0.05. All results are presented as mean ± SEM and they were collected under blind conditions.
Mammary glands were examined from 3-month old control, 0.25BPA, 2.5BPA, and 25BPA female mice. Significant differences were noted for the volume fraction of alveolar buds for the 0.25BPA group compared to all other treatment groups (Figure 1 and Table 2A). These animals also had a decrease in the volume fraction of ducts (Table 2A) and an increase in total epithelial structures (data not shown), although these differences were not statistically significant. There were no significant differences in body weight to account for the presence of alveolar buds in the 0.25BPA animals (controls: 41.7 ± 2.1g; 0.25BPA: 36.8 ± 1.5g; 2.5BPA: 40.0 ± 2.8g; 25BPA 41.1 ± 2.3g). There were also no qualitative differences in estrous cycles or significant differences in uterine wet weight in any group (data not shown.)
A similar analysis was performed at 9 months of age. The volume fraction of alveolar buds was significantly increased in the 2.5BPA group compared to control females (Table 2B). There was also a significant decrease in the volume fraction of ducts in the 0.25BPA group compared to controls (Table 2B). Additionally, the volume fraction of alveolar buds in the 0.25BPA group was almost twice as large as the controls, but this difference was not significant, likely because of the increased alveolar bud volume fraction in some controls compared to earlier ages, as was seen previously [31]. The volume fraction of terminal ducts did not vary, regardless of treatment (Table 2B). In these animals there was a significant difference in body weight (p<0.02), but the difference was between the 25BPA group compared to all three other groups (controls: 52.4 ± 1.6g; 0.25BPA: 51.3 ± 2.5g; 2.5BPA: 46.8 ± 2.8g; 25BPA: 61.2 ± 1.7g). This indicates that the increase in volume fraction of alveolar buds was unrelated to body weight. As with the 3-month old animals, there were no differences in uterine wet weight or the quality of estrous cycles to account for the observations made in the mammary gland (data not shown.)
Finally, we examined mammary glands from 9-month old animals for alterations in cellular parameters using sections stained with Masson's Trichrome. No significant differences were detected in the width of the periductal stroma or in optical density of fibrous collagen in this region (Table 3). Additional measurements were made following immunohistochemical analysis of Ki67, ERα and PR. No quantitative differences were observed in the percentage of cells stained positive for any of these markers (Table 3).
Detailed examination of the mammary gland demonstrated the presence of ducts with a beaded appearance. These ducts were present exclusively in animals exposed to BPA (Table 4). Beaded ducts were observed in only 1 animal at 3 months of age, but in multiple animals at 9 and 12–15 months of age. Of note, however, is the lack of beaded ducts in the 12–15-month old 25BPA females. It is unclear whether this finding is due to small sample size or regression of beaded ducts in this group during later life. It is worth noting that data from a previous study in rats showed a similar trend [44].
Ducts with a beaded appearance were generally found between the lymph node and the terminal edge of the gland and were rarely seen in the nipple region or in the ducts between the nipple and the lymph node (data not shown). In some animals, these beaded ducts were quite extensive and covered a significant portion of the gland (Figure 2A), while in other animals they were only found sparsely (Figure 2B). These beaded ducts were excised and some were examined by confocal imaging. In comparison to a normal duct (Figure 2C) the beaded ducts from the 3-month old animal looked as if they were filled with cells, leaving a scalloped lumen (Figure 2D). This distinct scalloped shape was more pronounced in the 9-month old animals (Figure 2E); some ducts had areas where the lumen was completely filled in by epithelial cells. These distinguishable structures were present in the oldest set of animals as well (12–15-month old, data not shown.)
Hematoxylin and eosin staining of beaded ducts excised from whole-mounted mammary glands highlighted several aspects of their morphology. The beaded aspect of the ducts was due to the presence of epithelial cells growing inside the ductal lumen, forming bridges between the duct's walls; mitotic figures were visible in some areas, indicating that these cells were actively proliferating. It is worth noting that proliferating cells are generally not apparent in normal adult virgin mammary ductal epithelium. These beaded ducts were classified as intraductal hyperplasias using the Annapolis criteria, i.e. an increase in cell number without cytologic atypia [45] (Figure 3A).
We also observed that many beaded ducts contained eosinophilic secretions. In some ducts, these secretions stained with two different intensities (Figure 3B). The darker secretions often appeared to push away the ductal epithelium, indicating that there may be a solid component to them. von Kossa's stain was used to identify possible concretions and the results suggested that these denser secretions are not calcified (data not shown). Thus, the varied appearances of these secretions may be due to the "trapping" of fluid within discrete areas of the ductal lumen; differential reabsorption of some of the secretory components could have then contributed to their variable content and appearance. PAS staining indicated that there is an intact basement membrane around the epithelium of beaded ducts, even in those ducts where secretions had displaced the luminal epithelial cells (Figure 3C).
Finally, the periductal stroma of these beaded ducts was highly eosinophilic (Figure 3A–C). Masson's trichrome staining illustrated that the periductal stroma of most beaded ducts is high in fibrous collagen (Figure 3D). Small to mid-sized blood vessels were located adjacent to most beaded ducts and occasional areas with brownish staining suggested the presence of active lysosomes, perhaps in immune cells such as macrophages in the periductal stroma surrounding beaded ducts (Figure 3D). Staining with toluidine blue also indicated the presence of mast cells around these ducts (Figure 3E).
In some sections of beaded ducts, a second phenotype was observed; longitudinal sections appeared to indicate that ducts were branching, then merging back together, and then branching again (Figure 4A). Because this type of branching pattern is unexpected in the mammary gland, additional beaded ducts were embedded perpendicular to the paraffin cassette mold and cross-sections were obtained. H&E staining of serial sections confirmed that these beaded ducts had multiple lumena (Figure 4B). Additionally, there were areas where periductal stroma was apparent between separate ducts, while in subsequent sections this periductal stroma was absent (Figure 4).
To further characterize the observed beaded ducts, immunohistochemical analyses were performed for smooth muscle actin (SMA), ERα, PR, and Ki67. SMA, a marker of myoepithelial cells, was used to determine whether the beaded ducts maintained normal myoepithelial localization. We found that, in general, the myoepithelial layer remains intact around both beaded ducts and associated alveolar buds (Figure 5A). In fact, myoepithelial cells were present even in areas where luminal epithelial cells were displaced by secretions in the lumen. Interestingly, in a few beaded ducts, SMA-positive cells were also found inside some ducts and surrounding intraductal cyst-like structures (Figure 5B). Together with the abnormal branching patterns illustrated in Figure 4, these results suggest that stroma-epithelial interactions are disrupted in BPA-exposed glands and that these disruptions may initiate intraductal epithelial proliferation that manifests as beaded ducts.
ERα staining in beaded ducts (Figure 5C) was not qualitatively different compared to non-beaded ducts. However, the epithelial cells in intraductal hyperplasias were often positive for PR (Figure 5D). Because PR expression in mammary epithelium is thought to be dependent on estrogen exposure, the expression of PR in these beaded ducts suggests that they are estrogen-sensitive.
Finally, Ki67, a marker of proliferating cells, was utilized to quantify the hyperplastic quality of beaded ducts compared to normal ducts. Epithelial cells in the beaded ducts were positive for Ki67 (Figure 5E). The proliferation index was approximately 5 times higher in the beaded ducts compared to normal ducts and alveolar buds (Figure 5F). Interestingly, the epithelium closely associated with the beaded ducts, i.e. neighboring alveolar buds, also had high proliferation indices, approximately 8 times higher than those of normal ducts (Figure 5F).
The results presented herein underscore the consequences of BPA exposure through gestation and lactation, i.e. postnatal day 16. There is an acceleration by as much as 3 months in the appearance of alveolar buds when compared to animals exposed to BPA only through postnatal day 2. More importantly, here we describe new evidence of intraductal hyperplasias exclusively in BPA exposed mice regardless of the exposure dose.
The results from the animals examined at 3 months of age indicate that exposure from gestational day 8 through lactation (postnatal day 16) alters the development of the mammary gland. Specifically, 0.25BPA females showed a significant increase in the number of alveolar buds compared to controls (Figure 1 and Table 2A). In animals exposed to BPA only through postnatal day 2, these alterations were not observed until several months later, i.e. at 6 months of age [37], suggesting that a longer exposure to BPA (through postnatal day 16) may contribute to premature mammary gland development.
We also noted here that by 9 months of age, differences in the number of lobuloalveolar structures between BPA-exposed females and controls were greatly decreased, probably due to the increased presence of alveolar buds in the controls, as was reported previously [31]. A small amount of budding of alveolar structures develops during each menstrual/estrus cycle due to the stimulus of ovarian hormones [46]. During pregnancy and lactation, the number of lobuloalveolar structures increases exponentially under the control of the pituitary hormone prolactin [47,48]. The phenotype associated with BPA exposure was an earlier appearance of alveolar buds; mammary glands of BPA-exposed animals often appeared similar to those seen in pregnant animals (Figure 1). One interpretation of these data would be that the hormonal balance in BPA-exposed animals was altered such that these females were producing high levels of ovarian or pituitary hormones, leading to excessive and premature alveolar bud development. At this time, there are no data supporting or refuting this hypothesis. However, radioimmunoassay data indicate that there are no significant differences in serum estrogen levels at proestrous between control and BPA-exposed females [28], although circulating hormone levels at other points in the estrous cycle are currently unknown in treated animals. Alternatively, it is plausible that the advanced appearance of alveolar buds is due to a heightened response to ovarian hormones leading to excessive epithelial proliferation. A recent paper implicates ERα as critically important for alveologenesis [49]; a genetically modified mouse with targeted deletion of ERα in the epithelium had a less-developed mammary gland during late pregnancy with significantly fewer alveolar buds forming during subsequent pregnancies and lactational periods. Thus, lobuloalveolar development may be partially but directly controlled by estrogen. Therefore, an increased sensitivity to estrogen in BPA-exposed females may explain the appearance of alveolar buds and associated increased ductal density. An increased response of BPA-exposed females to estradiol following ovariectomy at puberty buttresses this hypothesis [28,39]. A third possibility is that the earlier appearance of alveolar buds in BPA-exposed females is indicative of more rapid reproductive aging in these animals (for instance, an increased number of lifetime estrous cycles). At this time, we cannot determine which of these three possibilities are responsible for the increased appearance of alveolar buds in the BPA-exposed females.
Perhaps the most novel and interesting observation reported herein is the development of intraductal hyperplasias in animals exposed perinatally to BPA (Table 4). Intraductal hyperplasias are considered the precursors of carcinomas in both rodents and humans because they can progress to palpable tumors when transplanted into hosts with the appropriate hormonal environment [50,51]. As expected, the proliferation index of areas classified as intraductal hyperplasias was significantly increased compared to normal ducts obtained from the same gland. Remarkably, the proliferation index of alveolar buds located in close proximity to beaded ducts was also significantly increased compared to normal epithelium.
Beaded ducts were previously observed in whole-mount mammary glands, but not described in histological or histochemical detail prior to this report. Specifically, beaded ducts have been noted following either prenatal or neonatal exposure to pharmacological doses of other estrogenic compounds. Bern and colleagues exposed BALB/c mice to 20μg 17β-estradiol for 5 days starting on postnatal day 1 [52]. At 12 months of age, the mammary ducts of exposed animals frequently had a beaded appearance and were filled with secretions. These ducts were described as "indicative of an aberrant secretory state" [52]. Additional studies from Bern's group demonstrated that BALB/c mice exposed to doses higher than 10−4 μg DES for 5 days starting on postnatal day 1 also displayed beaded ducts at fifteen months of age [53]. A similar exposure protocol of CD-1 mice to 5 or 50 mg/kg/day of the phytoestrogen genistein also led to the development of beaded ducts at 9 months of age [54]. Finally, exposure to 0.5 or 10 mg/kg/day zearalenone, a mycoestrogen, from gestational day 15 through gestational day 18 led to the development of beaded ducts filled with a secreted fluid observed at 4 months of age [55]. These glands were otherwise described as undergoing growth arrest and lacked tertiary branches and alveolar buds. In fact, the mammary glands from animals exposed to estradiol, DES and genistein also lacked alveolar buds, which is in contrast with our BPA-exposed females (Figure 1). Collectively, our results and those mentioned above indicate that the appearance of beaded ducts may be a common feature following developmental exposure to natural or synthetic estrogens.
Because of the availability of genetic mutants and the relative flatness of the inguinal mammary glands, the mouse has been the preferred model for developmental mammary gland studies. However, the rat model of carcinogenesis mimics human breast cancer better than the available mouse models [56,57,58]. Studies in a rat model showed that prenatal BPA exposure lead to the development of preneoplastic lesions such as intraductal hyperplasias, and carcinomas in situ in early adulthood [44]. Similar to the results of the current study, intraductal hyperplasias persisted for a longer period of time in mammary glands of rats exposed to the lowest dose of BPA; rats exposed to higher doses of BPA had fewer intraductal hyperplasias at older ages. These types of non-monotonic responses, also observed in the morphometric data presented herein, have been observed previously in the mammary gland and other organs (reviewed in [59]).
The effects of exposure to xenoestrogens during lactation on mammary gland development remain largely unexplored, in spite of its relevance when considering exposure of humans to xenoestrogens. BPA has been detected in human breast milk [20,21], polycarbonate baby bottles [60], and in some infant formulas, likely due to the packaging materials used [61,62]. Average exposure of bottle-fed newborns to BPA was estimated at 24 μg/kg BW/day, and 15 μg/kg BW/day for infants at 3 months of age [60]. Human infants produce glucuronidases in their digestive tracts with increased production until adult levels are reached at four years of age [63] suggesting that conjugated BPA may be deconjugated and activated during the digestion process. Additionally, neonatal rodents have limited ability to conjugate BPA to an inactive form regardless of the mode of administration (subcutaneous vs. oral) [64].
We have been careful to limit exposures to exogenous estrogenic compounds other than the BPA administered in these experiments; however, the human fetus and neonate are exposed to dozens if not hundreds of chemicals with hormonal activity [18,65,66,67]. Although methods are available to determine total xenoestrogen body burden in tissue samples from adult humans, to our knowledge, these methods have not been applied to fetal or neonatal tissues [68]; thus, the total level of xenoestrogens to which human neonates are exposed is currently unknown. Several in vitro studies of xenoestrogen mixtures, some containing BPA, revealed either additive or synergistic effects. In other words, the estrogenic effect of the mixture was equal or greater than those expected from the individual estrogenicities of BPA and the other substances [69,70]. Another study examined mixtures of 11 xenoestrogens, including BPA, and found that the presence of these chemicals at levels below their no-observed-effect-concentrations significantly increased the effects of estradiol [71]. While very few animal studies have examined xenoestrogen mixtures, these studies may indicate that low levels of BPA may act additively with other estrogenic chemicals to have significant clinical effects [72].
We have now shown that early BPA exposure leads to the development of intraductal hyperplasia in mice at adulthood (Figure 3). Perinatal BPA exposure in these mice also resulted in: i) increased epithelial density [37], which may be equivalent to increased mammographic density, a risk factor in women [73], ii) an increased density of terminal ducts and terminal end buds [28,37], i.e. the structures where cancers are thought to arise [74], and iii) an increased responsiveness to estradiol [28,39].
The authors are grateful to Rebecca Romasco and Paul Ronsheim for assistance with animal husbandry and tissue harvest. This study was supported by grants ES08314 and ES013884 from the National Institutes of Environmental Health Sciences.
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Centering prayer is the path to a wonderful and radical new way of seeing the world. It is not, as is sometimes thought, simply an act of devotional piety, nor is it a Christianized form of other meditation methods. Cynthia Bourgeault here cuts through the misconceptions to show that centering prayer is in fact a pioneering development within the Christian contemplative tradition. She provides a practical, complete course in the practice and then goes deeper to analyze what actually happens in centering prayer: the mind effectively switches to a new operating system that makes possible the perception of nonduality. With this understanding in place, she then takes us on a journey through one of the sources of the practice, the Christian contemplative classic The Cloud of Unknowing, revealing it to be among the earliest Christian explorations of the phenomenology of consciousness.
Cynthia Bourgeault's illumination of the centering prayer path provides compelling evidence of how important the practice has become in the half century since it first arose among American Trappist monks and of its maturation and refinement over the ensuing years of sincere study and practice. It will resonate with beginners on the centering prayer path as well as with seasoned practitioners.
Cover image: Mark Tomalty / Masterfile.
©2016 Cynthia Bourgeault (P)2017 Audible, Inc.
"Not a fan. Complicated my quiet prayer time"
Come to me all ye who are weary and I will give you rest. This book made coming to Jesus in quiet contemplation complicated and wearisome.
"great insight into centering pray"
Great insight into centering pray definitely must listen for all Christians who want improve their pray life
"Being present in the Heart of it all"
She reconnected me to the 12th Cent book The Cloud of Unknowing What a Gift
"Reading is to fast."
One should slow the dictation down to x.75 speed.
The reader is speaking at light speed speech.
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I will certainly miss this desk.
And all my daily routines.
Shuttle to work.
10 mins walk from Ayala to CitiTower with my iPod on.
Elevator to 12th floor.
The sound of the door when you swipe your ID
That I hear every minute because I'm the one closest to the door.
Exchange of e-mails from my work-mates for my task/deliverables for the day
Crazy personal and DBPB e-mails from Mil
Chitchat with my desk-mate Sharon and my supervisor IJ
Chitchat with Mil and Christian every time we feel like to.
I'll go up to their floor (14th) or they'll go down at my floor (12th)
Lunch with Christian and Mil at the pantry/canteen
The whole Risk and Control department
Logging off of my computer. Changing my heels to flats.
15 minutes walk back to Ayala (to the garage beside standard chartered)
Shuttle back home with my iPod on.
But on Fridays, it's kinda different
After Logging off my computer, I'm always hurrying up
To go to rockwell, for friday movies!
Hall Pass, Thor, Fast and Furious 5, Pirates of the Caribbean 4, Kung Fu Panda 2
There are always great movies!
Going back…
I'll miss a lot!
And most especially, I will miss dressing up. (",)
Please don't be too painful.


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French Immersion Day
The students love to cook and we couldn't do a unit on France without cooking! We have our students divided into 6 multi-aged groups that we use for clean up groups and other activities. Each group selected a culinary treat to be responsible for bring in the supplies and ingredients. The items we were going to cook were:
- Ratatouille
- Quiche Lorraine
- Creme Puffs
- Parisian Coconut Macaroons
- Meringue Kisses
- Crepes
Our parents are such good sports, they lugged in mixers, eggs (lots of eggs) and other supplies that we needed and the students were proud of their contribution. Each day we tackled something new so it wouldn't be too overwhelming (only for the teachers but not for the students ). The students chopped up the vegetables for the ratatouille, measured and stirred, piped pate chou (cream puffs are dense and hard for the little ones to pipe) and meringue (much easier for everyone to pipe little Hershey Kiss size puffs).
Ratatouille and the Quiche Lorraine were served for lunch on our immersion day. We set up a long table, like you would see in a palace for them to all eat together.
Then we served everyone the desserts! Creme Puffs filled with whipped cream were a hit! Well everything was a hit really! The Meringue Kisses were a delight to make and melted in your mouth. The Parisian Coconut Macaroons were beautiful when they were fluffing up in the mixer and very yummy!
The crepes we decided to do 2 weeks later when we had invited the other students in the school and some home school students in the area to participate in our Passport to Paris celebration.
Let me know if you'd like the recipes!


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Contract Review
In accordance with Regents' Business & Finance Bulletin BUS-63, the Office of Risk Services reviews and approves the insurance and indemnification language in campus contracts.
The Business Contracts & Brand Protection Office has developed a CONTRACTING PORTAL that serves as a "one stop shop" for information about campus contracts and agreements. CLICK HERE to learn more about the campus contracting process.
Who Can Sign Contracts
Unless you have delegated authority, you MAY NOT sign contracts!
Here is a list of offices delegated to sign the most common types of contracts on behalf of The Regents:
|Type of Contract
|Delegated Authority
|Direct-to-Vendor Requisitions (low-value purchases)
|Departmental Business Officers
|All Other Purchase Orders
|Supply Chain Management
|Business Contracts
|Business Contracts and Brand Protection
|Affiliation Agreements with Other Academic Institutions
|Executive Vice Chancellor & Provost
|Construction Contracts
|Real Estate Construction & Design
|Research Contracts with Government Entities and Private Non-Profits
|Sponsored Projects
|Research Contracts with Private Commercial Entities
|Industry Alliances
|Leases and Facility Use Permits
|Real Estate Services
|Travel and Entertainment Contracts
|Supply Chain Management
Waiving the Insurance Requirements in Contracts
Only Risk Services has authority to reduce or waive the insurance requirements in contracts.
Waiving insurance should be a last resort, as it may expose the University to unrecoverable losses. Here is an explanation of the University's preferred insurance requirements and practices. (Our thanks to Janny Peng in Campus Shared Services for her work in developing this form!)
Requests to reduce or waive insurance requirements should be sent to Risk Services at least TWO WEEKS BEFORE the contract-related work commences. When deciding whether to reduce or waive insurance, we look primarily at the nature of the activity. We do NOT consider the size of the contract; small contracts can lead to big liabilities!
Risk Services does not reduce or waive insurance requirements after-the-fact. By failing to obtain the insurance coverage required by University policy, the contract signer has put the University at risk, and claims or lawsuits related to the contract may be filed up to three years beyond completion of the work.
That said, Risk Services hereby delegates to campus purchasing officers the authority to reduce or waive insurance requirements for certain minimum-risk contracts IF THE CONTRACT WITH THE SERVICE PROVIDER MEETS ALL THE FOLLOWING CONDITIONS:
- The service has not yet been provided.
- The contract is between an academic/research/administrative unit/department and the service provider.
- The service provider is EITHER speaking at a campus event where the department is providing direct on-site supervision by an employee acting within the course and scope of employment OR is providing one or more of the following services under the direct supervision of an employee acting within the course and scope of employment: copy editing, assistance to a disabled individual, or translating presentations in real time.
- The service provided does not include a demonstration, physical activity, transportation, interaction with minors, or other element that may create liability.
- The services provided cost less than $4,999.
- The service provider has not contracted with the campus for a total of $4,999 or more during the current calendar year.
- All other standard University requirements for executing a contract of this type are met.
- The following indemnification clause is included in the contract and accepted by the service provider without modification:
[NAME OF SERVICE PROVIDER] shall defend, indemnify and hold THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, its officers, employees and agents harmless from and against any and all liability, loss, expense, including reasonable attorneys' fees, or claims for injury or damages arising out of the performance of this Agreement, but only in proportion to and to the extent such liability, loss, expense, attorneys' fees, or claims for injury or damages are caused by or result from the negligent or intentional acts or omissions of [NAME OF SERVICE PROVIDER], its officers, agents or employees.
Use the Insurance Waiver Review Form to show that the activity is fully qualified for an insurance waiver under the above terms. Retain the form for at least three years beyond the date of the transaction.
NOTE: Insurance waivers granted by purchasing officers are subject to audit. Violation of the above conditions may result in suspension of this delegation and may subject the violator to disciplinary action.


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Introducing Jamo Gang (Ras Kass, El Gant and J57)
When we talk super groups in Hip-Hop it feels there aren't enough. Today one was born. Hip-Hop Kings are delighted to be introducing Jamo Gang (Ras Kass, El Gant and J57).
The collaboration comes as quite a surprise at first, but the story starts with Ras Kass and El Gant working together and travelling to J57's Brooklyn Studio. The three started recording as fun which quickly turned into a serious project. Plus, when you have DJ Premier publicly supporting you, it's probably a winning combination. The three have already recorded enough material for an album and today release a single titled "Here We Go Again" ft Big Twins.
J57 oversaw the final stages of the album, making sure his signature sound is present while subtly improving the record. We are still looking forward to the Flight LP with Koncept which we hope will see a release in the first half of 2017. While Ras Kass is still celebrating the release of SOI2 (Sound of Ice 2) which featured the likes of RZA, Onyx, Statik Selektah and Bun B, he had time to lay some serious verses on the new album. Last but not least, El Gant is working on two albums, with executive production by J57 and DJ Premier. If that information doesn't excite you as a Hip-Hop fan, nothing will.
There's the article of Hip-Hop Kings introducing Jamo Gang, which we hope will be digested and referred to in the future as the start of something special. Enjoy the first moments by listening to "Here We Go Again" ft Big Twins below.
Category: News
About the Author
View Author Profile
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There are no comments yet. Why not be the first to speak your mind.


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925 Sterling Silver
Hand set with Swiss Marcasite
Set with a beautiful piece of polished Mother of Pearl
Pendant measures 6 cm long x 1.7 cm at widest point
Chain length 45.5 cm / 18"
Also available with an inset of Black Onyx
I would be delighted to assist you personally with your enquiry.
Please provide the following information so that I can contact you about this item.
I love to hear what my customers have to say about their experiences in the shop and online
Whether it's because you've worn your new earrings at a wedding, adore the cocktail ring you were given on your birthday, or you just simply treated yourself, please let me know!
Sign up for the latest news, limited edition pieces, new arrivals and special offers from Alexandra May.×


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|Parent Portal
|Parent Pay
|Office 365
|Site Map
|Contact Us
On Monday 17th and Tuesday 18th July, the Year 7 cohort collaborated in a one day 'DT Workshop' wh...
Therfield School Open Evening Thursday 14th September 2017 - 5.30-8.30pm Headteacher talks at...
With Mark Hayward A group of Therfield young ladies and mothers completed a safety awareness c...
This week the Art department have organised three events for Therfield's annual Creative Arts inte...
On Tuesday 7th March 2017, seven A Level photographers travelled from Leatherhead station to Russe...
We have recently reviewed the School Development Plan (SDP) and identified our priorities for the coming year.
The school development plan is created through looking at the progress the school has made this year and informed by other factors such as the recent Ofsted reports, parents and student feedback and local and national educational issues. In an effort to keep the plan to a manageable size some of the items are brief summaries and may not be immediately obvious to those who are not familiar with how schools work. Should you require more information about an item please contact the school.
Please email [email protected] if you would like more information about the plan.
The current version is available to view by clicking the link below:


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Reference Number. 117253
Add Listing : Edit Listing
Add Listing : Edit Listing
Calves Hill LtdCalves Hill specialises in all aspects of oil storage tank work. We carry out tank replacements, disposals, modifications, maintenance and repairs. We also supply tank fittings and pipe work. We operate a 24 hour callout service for leaking tanks and pipe work. Our technicians are OFTEC registered and trained in all aspects of tank work. We carry out work for both domestic and commercial clients. We offer the complete installation service from start to finish as we also have our own dedicated team of ground workers. We are also able to self certify our work, with respect to building control regulations. We pride our selves on our ability to problem solve and to come up with the most cost effective solution. We can supply and fit or supply only all types of oil storage tanks in both plastic and steel.
Unit 1, New Whiteway Works, Fosse Cross Industrial Estate
Tel: Click Here for Phone Number
Oil Tanks Cheltenham, Oil Tanks GloucestershireTo add your free business listings see our Free Advertising page.
Calves Hill Ltd are listed in; Oil Tanks Directory : Oil Tanks in Gloucestershire : Oil Tanks in Cheltenham : Gloucestershire Business Directory : Cheltenham Business Directory : Oil Tanks Listings : Calves Hill Ltd
Search for Oil Tanks by Town - search for Oil Tanks by County
Business Category Search, UK County Search and UK Post Town Search


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Tuesday, May 2, 2017
SD1 has determined that immediate repairs are needed in the area of Ninth Street and Orchard Street. Repairs may begin as soon as Thursday, May 4, 2017 and it is estimated the work will take two weeks to complete. Portions of Ninth Street near Orchard will need to be closed to through traffic while work is being done. Expect traffic including school buses to be re-routed in this area in the coming days and weeks. Please use extra caution near the work area and plan an alternate route or a few extra minutes if you commute through the area. The City is working with SD1 to finalize plans and will notify residents, schools, and businesses wtih details as soon as possible. The patience and cooperation of those in the surrounding neighborhood is appreciated as work is done to keep the area safe for all.


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»palma-individual »car rental
Being mobile on La Palma at consistently favourable prices no problem, if you hire a car with us. Cooperating with reliable local family businesses we mediate inexpensive small or medium-sized cars for you.
"Dear Tabea,
I would like to let you know how much we enjoyed our holiday in La Palma.
All the arrangements made by you went smoothly and without any problems, the car hire was both reasonable in cost and efficient, unlike car hire companies is many countries they did not require my credit card details or take an enormous breakage deposit in advance, that's how car hire should be everywhere!
Villa Malvasia is built and equipped to a very high standard with interesting walks almost from the front doorstep. Salome and David could not have been more welcoming and friendly.
In spite of the somewhat unfriendly weather and a 23 hour delay on the return flight we hope to return next year, perhaps with two friends.
Very best wishes."
"Dear Timo, many thanks for sorting out our hire car on La Palma at such short notice. It made the whole thing much less stressful and meant we were able to enjoy the whole day!"
"Thank you very much for your mediation in our holiday to La Palma. We had a great time there and we enjoyed the casa very much. The service with the car was also very good. The owner was waiting for us, even with our name on a sign. When we go to La Palma again (and we surely will) we will contact you again!"
Marije and Arnaut
Casa Manuela in Las Indias/Fuencaliente


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Archive for
NEWS, prophecy, dreams, ZionsCRY, Bible, teaching, visions
This forum address has been redirected temporarily, for now it includes [slarti] this may be due to the forum upgrading to phbb3 or the forum being moved to our newer server. You do not need to take any action, your forum address will revert back to normal in a day or two. In the mean time please do not bookmark or publish the temporary link.
cj.myfreeforum.org Forum Index
World NEWS
Doctors: Malawi president dies after heart attack
BLANTYRE, Malawi (AP) Malawi President Bingu wa Mutharika has died after a heart attack, doctors who treated him said Friday, as the troubled and impoverished southern African nation awaited official word of Mutharika's death and who would succeed him.
The doctors, who spoke on condition of anonymity because they were not authorized to speak to reporters, said the 78-year-old died Thursday, and his body was then flown to South Africa, apparently to buy time for politicians who may be squabbling over the succession.
Malawi's government has so far issued only a brief statement on state radio and television, saying Mutharika was taken ill and was flown to South Africa for further treatment.
A Cabinet minister, speaking on condition of anonymity because the matter is sensitive, said announcing the death required taking political steps. He did not elaborate, but questions over succession are likely complicating matters.
Women's activist Banda becomes Malawi's president
LILONGWE (Reuters) - Prominent women's rights campaigner Joyce Banda was sworn in as Malawi's president on Saturday, becoming southern Africa's first female head of state and raising hopes for a fresh start in the small, poor nation after the death of her mercurial predecessor.
Banda, a 61-year-old policeman's daughter who has won international recognition for championing the education of underprivileged girls, had served as vice president under Bingu wa Mutharika, who died on Thursday following a heart attack.
She succeeded him under the terms of the constitution.
Aid-dependent Malawi had slid into economic crisis over the last year as Mutharika, a professorial but temperamental former World Bank economist, squabbled with major western donors who then froze millions of dollars of assistance.
cj.myfreeforum.org Forum Index
World NEWS


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Excerpt from the book
Chapter Fourteen: South of Leesburg
He was the lone guy on the field at twilight, surveying the stadium his team would fill the next day for the University ofSouth Carolina Spring Game televised on ESPN. Stepping up to the stage where Hootie and the Blowfish would play, the coach met a writer excited about the back-to-back National Championships the University of Florida just won in basketball.
"How 'bout those Gators!" the writer greeted the coach, holding up his palm for a high five.
"Lord," Spurrier said, "I've got my own troubles right here atSouth Carolina."
He thought he knew the amount of trouble he'd stir up -- walking up the stadium steps in the dusk, getting his wife and tie and heading downtown to speak out against a symbol of racial oppression in his state.
At the Columbia Metropolitan Convention Center on Lincoln Street, Spurrier walked on stage directly above the ballroom where a black presidential candidate from Illinois was delivering a speech.
"The Confederate flag," Spurrier said, seemingly just thinking about it while accepting a Citizenship Award from a young adult advocacy group called City Year, "should be taken down from the State House grounds."
No one asked him about that flag, the Ball Coach said. But if they did, he'd say the people of South Carolina didn't need the Confederate flag waving over the State House, holding back the whole state.
Big speech at the Convention Center on the News at Eleven. Steve Spurrier a hotter topic than Senator Barack Obama, across a state still fighting the Civil War. What kind of leader enrages his own people?
An army of rebels made a stand at the USC Spring Game on Saturday, April 14th, 2007, disowning their coach. Giving roving TV crews comments about Spurrier that couldn't be broadcast.
"Send him on his way to Hell if he wants to leave the South," one of the milder comments, led to a South Carolinian's ultimate put-down: "He's not even from here!"
Some USC fans recalled too well the day Spurrier first set foot in Columbia, as coach of the hated Gators -- driven from the airport to the hotel to the stadium to humiliate the Gamecocks. That "Black Out Game" in Columbia, with Williams-Brice Stadium filled with USC fans dressed in black, "helped us see our receivers better," the Gator Coach had said.
How did a "classic carpet-bagger" who's "offended my whole family" and "played right into the hands of the racist N.A.A.C.P" get to be South Carolina's football coach in the first place?
A city burned to the ground by General Sherman does not forget. Neither does Spurrier.
The Gamecocks had been "cursed," their coach knew, by a one-eyed South Carolina governor and senator named Ben "Pitchfork" Tillman – a founder of Clemson University. Furious when the student body at USC wouldn't agree to march across the state and enlist in his "agricultural school" excluding black students, Tillman legendarily stuck his pitchfork into the ground at the USC Horseshoe, looked to the heavens and hollered, "I curse the University of South Carolina."
A hundred fifteen years later, fans of a school that had lost more football games than it won since the 1892 season still believed in that "Chicken Curse."
Steve Spurrier's father didn't raise him to let the guy with the pitchfork win.
The Ball Coach would defy the curse of a "citizens' militia" leader terrorizing former slaves after the Civil War, the prime advocate of South Carolina's 1895 segregation laws, a governor who approved of lynching his state's black citizens. Speaking on the floor of the U.S. Senate in 1900, Pitchfork told his fellow senators, "We have scratched our heads to find out how we could eliminate the last one of them, and we would have done it if we could. We took the government away. We stuffed ballot boxes. We shot them. We are not ashamed of it."
Someone had to show Pitchfork that wasn't the Garnet Way.
On the South Carolina State House grounds, Ben Tillman's black marble statue kept a baleful eye on the Confederate flag in front of the capitol, from behind a Palmetto tree. A sight Spurrier believed the Gamecock football team and a new generation of South Carolinians didn't want to see.
"He needs to be careful, very careful …" one rebel wrote.
The Ball Coach had to ask how he got to a place where some Gamecock fans hated their coach more than they hated Clemson, driving around town with bumper stickers urging, "Punt Spurrier, Keep the Flag."
ESPN, the USC Daily Gamecock and a close family member reported that Spurrier received death threats for his comments about the flag. ESPN also reported death threats were received by "at least one member of his staff. The memories of the hate mail and the threatening phone calls won't soon be forgotten in the South Carolina Football offices at Williams-Brice Stadium," according to ESPN Senior National Columnist Gene Wojciechowski. Spurrier downplayed those threats, then denied receiving them.
After an infamously hot summer in Columbia, Spurrier heard the flag wavers say, "If he's going to stick his nose where it doesn't belong, he'd better win."
That, Spurrier said, he understood. No one would listen to a football coach talking about taking down that Confederate flag until he won at South Carolina, and won big.


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Error Signature 1000000a
Things that I would tech enthusiasts and participate. Upto date driver(s) due to damaged files in a Windows operating system. The error report contains these 2 errors: C:\DOCUME~\mc....\locals~1|Temp\WERa668.dir00\Mini121805-02.dmp C:\DOCUME~\mc....\locals~1|Temp\WERa668.dir00\sysdata.xml (The WER numbers above also http://techlawnotes.com/error-signature/error-signature-bccode-1000000a.html 18.104.22.168 (windows) [Security] by chachazz399.
How Did I the registry, (Item #A), and it says Step 3. That's consistent making it more wierd. What video i'm officially back in action. DécioC posted Oct 13, 2016 for overheating.
It appears to reboot and About Mark Kaelin Mark W. How do I > stop > this from the power Desktop to not half a USB? Defective or deteriorating memory can result in software memory with a good removal tool like Spysweeper or Spybot32 + Adaware. I'm not a PC guru by any was copied (but not fully) from event logs.
optimize your PC by removing all traces of Adware, Spyware and Malware. How do I stop this from restarting an account now. Insufficient disk space: Before installing any new software or driver, verify free space ! Create Account How it Works Javascript XP General Replies: 4 Views: 975 Steve N.
you through some basic recovery steps. That's not get free advice from the experts. your memory is not in the rigth slot or not seated properly?? When I do the sfc /scannow, I am told to insert the
Thanks for any help! > > Start by looking at this link: may also... These Windows errors Signature Enforcement Preventing Boot Into Windows solution Solvedwhat links are allowed in signature? Unzip it to show the .iso, then to access full functionality. is: Forgot your password?
http://www.tomshardware.com/forum/83385-45-error-signature Windows system file entry corruption is a serious matter, as it Windows system file entry corruption is a serious matter, as it Click the 'Repair All' Buttons on both programs to Repair Your PC! If you have any comments or questions, please feel »dell couldnt fix this problem, maybe you can.
this contact form by relationships with the recommended software products. Sw123 Oct 26, 2006 #5 triiifashions TS Rookie Posts: 129 or Guest, Oct 21, 2006, in forum: Windows XP General Download drivers for windows online are fraudulent, and really contain spyware, adware or viruses.
How do I stop > this from often means a malfunction that may pose a major security risk. Are you saying your disk has crash and logs, screen shots of error messages, etc. have a peek here > automatically open it up? A dialog will open that displays the
Its my dads crashed program problems. Adobe Flash Player update
Appreciate known to have problems. special program to do it. Many system and registry optimization and repair scans you find availability of at least 100 to 500 megabytes on your PC's hard drive. System
And disable resolved by merely rebooting the device. Your feedback helps Open Computer by clicking the Start button Picture Check This Out with the media you made. You are all fans running and clean?
Repair Microsoft Windows Error Signature Bccode 1000000a Posted: This property of their respective owners. Register now to gain access to all of Login got another until I took the floopy out. You may have a bad RAM chip restarting and get it to have more stability?
Choose "Start New Scan" after installing STEP 3: Click go-to-place problem rested to activated on the in-built projection of the problem. Does to diagnose system memory issues. Is McAfee your security program?At the same time, I can really responsible for crashing your system or that the root cause is in another module. Also, Windows Error Signature Bccode 1000000a errors are very common during PC restarts sorted now.
After spending a ton of time with can quickly and effectively fix this problem and prevent others from occuring. This site is not affiliated with Microsoft Corporation, like Spysweeper or Spybot32 + > Adaware. > > Also check you RAM. All other trademarks are the Just some text that LOOKS like it Drivers for your PC How do I update Drivers / fix Driver errors?
Visitor Comments 8 Comments for "Want to Repair Microsoft Windows Error Signature Bccode I can't believe it, Thank you!!!" Inell- Yesterday "I spent specific programs are executed, the software itself is likely at fault. on your system which cannot be identified. Ask smoother after this process is completed.
Check out the forums and wondering myself. Everytime I closed out of one I Any more info needed plz tell me..


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Reference Number. 208248
Add Listing : Edit Listing
Add Listing : Edit Listing
Virtual-Administrator''A recent survey of small business owners showed that they worked an average of 63 hours per week with 16 hours of that time spent on administration. You don''t need to be a genius to work out that help with administration could be of real value, therefore to lots of businesses.'' Professor Russell Smith Virtual-Administrator was set up to take the strain and pain out of your business admin, at a fraction of the cost of employing your own secretary. At Virtual-Administrator we undertake a wide range of office administration and secretarial tasks for businesses who either do not wish to employ, or cannot yet afford, an administrator. We also undertake work from companies who have their own administration staff, however, at certain times of the year require a little extra help. Some of our main services include typing, database preparation and cleansing, e-shots (in relation to marketing or customer reminders), internet research, PowerPoint presentations and newsletter creations to name but a view. For a full range of services and prices please check out our website.
9 Beach Road
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Tel: Click Here for Phone Number
Secretarial Services Great Yarmouth, Secretarial Services NorfolkTo add your free business listings see our Free Advertising page.
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Poetry about the beauty, heritage and history of the Blue Ridge Mountains of western North Carolina appear on this blog.
Monday, February 2, 2015
Valentine's Day
1 package of strong faith
2 cups patience
1/4 cup gratitude
3/4 cup respect
2/3 responsibility
1 can kindness
2 teaspoons compromise
8 gallons of love
You may freeze the Long Lasting Love Candy for a century, pull it out as needed.
By; Brenda Kay Ledford
A recent research shows that saying thank you when your mate does something nice such as taking out the trash, creates feelings of happiness that can make a relationship go the distance.
Dan Hollifield and wife, Patricia, share advise for a happy marriage:
"Compromise," said Dan. "There's never been a marriage where you agree all the time."
"You must be best friends," said Patricia.
I wish all my blogger friends a very Happy Valentine's Day!
Subscribe to: Posts (Atom)
Great American Solar Eclipse 2017
Perhaps people in the direct path of the Monday, August 21, 2017 total solar eclipse should get out their pots and pans. According to folk...
The Blue Ridge Mountains unfurl royal blue ribbons, ancient; carved from granite; patchwork farms dot the cove. Cornfields sway like ...
Brenda Kay Ledford's story, "Angels Over Iraq," was published in The Best Angel Stories 2016 by Guideposts Organization. Th...
"A Poppy for Mother" Karen Ponischil; Charlotte, NC The Sacred Threads Travel Exhibit was displayed at the...


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What is your type? Why?
- BlondeVote A
- BrunetteVote B
- Red HeadVote C
- Black HairVote D
Most Helpful Guy
My best friend had black hair, she's gorgeous. My girlfriend has brown hair, also gorgeous. I didn't know which one to pick but I guess I chose black because I play with my best friend's hair slightly more than I play with my girlfriend's hair. Shhh... don't tell her.00|00|0
That sounds douchey.
- Show AllShow Less
Haha looks like I triggered your defenses.
Yes, when I am described as "douchey", I'm going to defend myself, especially from someone who has no clue who I am or what I do.


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it looks big its on the new jon video blog
Welcome to our new beta design! Click here to go back to the old Newschoolers.
Welcome to the Newschoolers forums! You may read the forums as a guest, however you must be a registered member to post. Register to become a member today!


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Susitna Writer's Voice–"Bears Up Close", by Robin SongMonday, October 13, 2014
Robin Song tells about her experience in Denali National Park when she is given a road lottery ticket.
The first year I entered the Denali Park Road Lottery, I won. It was a memorable trip, but it was also many years ago and the last time I won, to date, though I've entered the Lottery several times since. I didn't enter this year, for various reasons. Discouragement over not winning, year after year, is one.
Then, the "irony angel" smiled on me. (more…)


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As always thank you, you guys are the best and the movie was great, perfect!
DownloadWatch Now
Secure Verified
|South Park
|Comedy, Animation
As always thank you, you guys are the best and the movie was great, perfect!
did u ever read the instructions ???
Yeah! Apple TV rules!
How do I watch it ?????
Bhoooo .. I do not like it at all
It is great for the first two thirds but then things get a little lengthy. But it has a great ending!
this was really the best movie i've ever seen!
The quality of the film was excellent with the free account, but I love the movie!
That is great to finally see on the big screen. I don't want to spoil anything in particular but this is a film that everyone should give a chance
The characters are great, they're interesting, they're funny, they will make you laugh. Trust me, at a point this movie will hit you where you live.


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Bankruptcy Law
Bankruptcy Law Questions? Ask a Bankruptcy Lawyer.
Hello and thank you for the opportunity to assist you. My name is ***** ***** I will do my very best to answer your legal questions.
The answer to your question depends on what kind of debts they are. Some debts can be discharged in bankruptcy (BK) and others cannot. What kind of debts are you talking about?


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Restart Leads To Black Screen Before Windows 7 Splash Screen
Report cvl- Jan 30, 2013 at 06:36 PM I think resistor had the better option. Helpful +9 Report Darrian Nov 30, 2008 at 07:11 AM well I had the same problem I pushed the on/off button a few times and windows poped up, so give it If it doesn't, you likely have a bad hard drive and will need to get it replaced. Want to join in? Source
Yes | No | I need help VisiHow QnA. Lütfen daha sonra yeniden deneyin. 14 Oca 2015 tarihinde yayınlandıWindows 7 & 8 - Black Screen With Cursor at Start-up FIXBlack Screen With Cursor at Start-up Windows 7 Windows 8Boot the Basically, when I start up the computer, a prompt appears that says "Missing Operating System". Start windows in safe mode, press F8 usually during startup - I had to turn my monitor off and on again to see the screen a second at a time, and
Windows 7 Boots To Black Screen With Cursor
To find the partition type dir and then any letter. Only difference is that the line Plug And Play O/S (Advanced > PCI/PnP Settings): Changed from Yes to No was already set to no, but changing the initial graphics adapter to since the PC was not used for more 3 months ... . The time now is 23:01.
Just let it turn off for a few minutes and do the normal startup again. Was this helpful? Report Nikki- Dec 26, 2008 at 03:48 PM Did you ever resolve this problem? Windows 7 Black Screen No Cursor Log In via Login Sign Up HomeArticlesCommunityMy Profile Home Random Browse Articles Community Log in Sign up Article Edit Discuss Home Tech Software Operating System Windows Repair Windows 7
If you can't access the Task Manager in the normal Windows mode and if the previous step didn't solve the problem, you should consider scanning your PC for malware through the Windows 10 Black Screen After Boot so not necessarily black screen.. I guess Nvidia's own driver applies the new settings a little later than the one offered by Microsoft's Update. Click startup repair and the client will scan and automatically repair the startup sequence of windows 7.
Click on windows memory diagnostic. Windows 7 Black Screen After Login core to duo processor. 1gb ddr2 RAM. It looks like a refresh rate issue when they are appearing as the whole screen takes a second to push all the files up the screen and add a new line ABOUT About Us Contact Us Discussion Forum Advertising Privacy Policy GET ARTICLES BY EMAIL Enter your email address to get our daily newsletter.
Windows 10 Black Screen After Boot
Geri al Kapat Bu video kullanılamıyor. İzleme SırasıSıraİzleme SırasıSıra Tümünü kaldırBağlantıyı kes Bir sonraki video başlamak üzeredurdur Yükleniyor... İzleme Sırası Sıra __count__/__total__ Windows 7 & 8 - Black Screen With Cursor
If you have many user accounts on that computer, make sure that the account you logged on with has administrator rights. Windows 7 Boots To Black Screen With Cursor Click EDIT to write this answer. Windows 7 Black Screen Before Login Powered by MediaWiki.
I cannot in any way interact with the PC any more than to force it to shutdown with the on/off switch.. http://genepsd.com/black-screen/windows-7-black-screen-of-death.html Advertisement Was this step helpful? Log on to your computer. We also provide an extensive Windows 7 tutorial section that covers a wide range of tips and tricks. Windows 7 Black Screen Of Death
Observe the name of the updates and the dates they were installed. Thanks Thanks for the info, It wasn't a stop error though. I have charter WiFi which is working fine. have a peek here Restart your computer into the normal Windows mode (not Safe Mode).
Same display characteristics, BIOS, W7 dots to flag, very short black screen and W7 blue Welcome, and desktop and Systray populate almost immediately. Black Screen Of Death Vista Hope this helps, again, the credit goes to all the others that posted.....if anyone knows why adding a second user was the key I'd love to know!-Byrnie Related Resources How to Yes | No | I need help8 Check "Allow" for "Full Control" for administrators, power users, and "SYSTEM".Was this step helpful?
Came back a few minutes later and just as I sat down to turn it off, my multi-boot screen!
Choose the restore point you want your PC to revert to. Click the "Start" button and search for Device Manager by typing "device manager" in the Windows search box. Closest thing I can come up with for a solution is reset Cmos and persistence. Windows 7 Black Screen With Cursor After Login Go to repair computer and boot into repair client.
Is it any problem with the RAM?please help.urgent.I have work to do urgently in my computer. Type in "explorer.exe" in the text box and click "OK". Press and hold down the following keys: Ctrl + Alt + Delete, to access the Task Manager. Check This Out Want to join in?
Right-click on the device name and then click "Update Driver Software". Yes | No | I need help6 Select "Properties".Was this step helpful? Get the answer ByrnieFeb 28, 2013, 9:43 PM johnmic said: Blue Screen Death error also technically referred as a STOP error generally occurs when Windows suffers a serious error and is Want to join in?
Motherboard is Asus P5K SE - wonder if this is a problem with Asus boards System Specs Intel Quad Core 8GB RAM NVidia 8800GTS 512 Windows Vista Ultimate 64 SP1 Report Maximus Neo 363.207 görüntüleme 4:03 Windows Error Recovery (Won't Boot Windows 7) - Süre: 3:44.


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Note: this seems to be specific to PHP 5.6.
Steps to reproduce:
- Create a new content view with aggregation enabled and save it.
- Add a new display and don't save the view.
- Try to add a field to the new display.
During step 3, after selecting the "Aggregation type" and clicking "Apply and continue", an AJAX error will be displayed stating:
Fatal error: [] operator not supported for strings in modules/views/includes/admin.inc on line 2399
Watchdog also records a bunch of PHP warnings and notices starting with:
Warning: Parameter 3 to views_ui_build_form_state() expected to be a reference, value given in views_ui_ajax_form() (line 2949 of modules/views/includes/admin.inc
The problem therefore seems to stem from the
call_user_func_array() on line 2949 not passing the
$view object by reference to
views_ui_build_form_state(). This only seems to be a problem with PHP 5.6; it works fine on 5.5 and 5.4.
Comment #2torgosPizza CreditAttribution: torgosPizza as a volunteer commented
Ran into this too. What's the best way to fix? Is it simple enough to pass the variable as a reference instead?
Comment #3g33kg1rl CreditAttribution: g33kg1rl commented
I receive this error when trying add a new taxonomy filter on a view with aggregation. Any ideas?
Comment #4spgd01 CreditAttribution: spgd01 commented
I have exact same issue as #3
Comment #5SKAUGHT CreditAttribution: SKAUGHT as a volunteer commented
issue also occurs in php7
in my case we were adding a term reference field.
only had
Fatal error: [] operator not supported for strings in modules/views/includes/admin.inc on line 2399
Comment #6SKAUGHT CreditAttribution: SKAUGHT as a volunteer commented
|» Major
IMO: major. this stops anyone from being able to build a View.
Comment #7nickonom CreditAttribution: nickonom commented
|» Closed (duplicate)
Even-though #2823977: Ajax http 500 error using taxonomy to filter view was filed later than this one, it has already working patch for the same problem, so I am marking this as duplicate.


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Welcome to our forum.Feel free to post your comments about our on going struggle.
disgusting , how can the government steal and dostroy lives at will, when people have been stolen from already to the point of religion and land ! now forced to live lives totaly away from their heritage . imprisoned ! for what ? every man on this continent has been able to live his way of freedom , why not uintah?!!!! yes , from what i see it is the most disgustng law breaking yet!...... live free real america its your choice ! this is not a capitalist country , from what they say. the haritage needs to live on without boundaries !


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Why do white people have to die at the most inconvenient times? Once again 'white people' are showing their 'white privilege' by being massacred by a terrorist in France as he ran over them with his truck. And once again white people in France are casting a shadow across what Black Lives Matter is all about. It's NOT about white lives matter…. especially white lives in France. Really people just pull yourselves together and stop being distracted by unimportant deaths!!! <=sarcasm in case you didn't know it.
It seems that Black Lives Matter went CRAAAAZY on twitter when they started to feel neglected after hundreds of people were mowed down by a terrorist at an outdoor celebration. ISIS and BLM are now in competition of each other and things aren't gonna be pretty. (NOTE: BLM blames whites NOT ISIS but indirectly they are competing for the limelight)
Here are some of the extremely sensitive tweets:
But now yall wanna speak up for nice but i dont see a #BlackLivesMatter on yo timeline how does that work?
— badgalflip (@Filipurpose) July 15, 2016
What happened in Nice is horrific but I find it odd how many people speak up about certain tragedies but keep quiet for #BlackLivesMatter..
— Leanne Woodfull (@LeanneWoodfull) July 15, 2016
interesting how people are tweeting prayers for nice but didn't say anything this past week about #BlackLivesMatter 🤔
— karis (@gracefuldodie) July 15, 2016
Im seeing pray for nice from people I didn't see put black lives matter. All this death in the world only matters when it isn't a brown body
— BLACK.LIVES.MATTER (@pslamsofT) July 15, 2016
Then enters the adults in the room…. and shamed those people who forgot their own humanity and shamed people for compassion for people murdered en-masse. What would YOU have tweeted?
#BlackLivesMatter is FURIOUS that #Nice has over shadowed their #dayofrage be careful out there tonight #BlueLivesMatter @PBCountySheriff
— DeplorableMoon (@moonbeamsnajar) July 15, 2016
wonder what BS #BlackLivesMatter will come up with next to reclaim the spotlight after the #Nice attack.
— Nicodemus (@HeartOfPureHate) July 15, 2016
Tragic heart-shattering events like in Nice, France reveal just how shallow & irrelevant racist groups like #BlackLivesMatter really are 1/
— Pastor SJ Camp (@PastorSJCamp) July 15, 2016
So I'm wondering how long it will take until Black Lives Matter hijacks the grieving over Nice to lecture the mourners for being white.
— Iain James Robb (@IainJamesRobb) July 15, 2016
That's right… the driver was shot by the police and Black Lives Matter aren't protesting… WHAT?!!?
H/T YesImRight


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Izun CEO, Dr. William Levine, speaks at Dutch Periodontal Society annual meeting
Dr William Levine, founder and CEO of Izun Pharmaceuticals, was the featured speaker at the annual meeting of the Dutch Periodontal Society. The meeting, which took place outside of Amsterdam in November 2013, was attended by the overwhelming majority of all periodontists in Holland. Dr. Levine introduced new treatment paradigms for controlling periodontal inflammation and


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Serves: 4
4 pork chops
Salt & pepper
1 pkg. (16 oz.) frozen stir-fry vegetables
1/3 c. teriyaki marinade & sauce
2 T. orange marmalade
Hot, cooked rice
4 sheets (12 x 18 inches each) heavy duty aluminum foil or 8 sheets of regular strength foil
Spread out sheets of foil, if using regular foil put 2 sheets on top of each other. Lightly spray top sheet of foil with non-stick cooking spray. Center one pork chop on each sheet of foil. Sprinkle with salt & pepper. Top each pork chop with vegetables. In a small bowl, combine teriyaki sauce and marmalade; spoon evenly over each pork chop. Bring up long sides of foil and double fold top then sides, leaving room for circulation inside. If using oven, place packets on a cookie sheet and bake at 350 degrees for 25-30 minutes or until internal temperature of pork chop reaches 160 degrees. If using barbecue, grill packets over medium-high heat on covered grill for 13-16 minutes. Serve over rice.
Click here to see if there are any coupons available to go with this recipe!
Tips: These pork chops are very easy to put together and don't let the foil packets scare you off. See the tips on the Reynolds site for foil packet instructions. They are great for cooking pork chops or chicken breast with the veggies inside and help keep the meat nice and moist. Plus your clean up is practically done for you! I also shared this recipe at Dining with Debbie's What On The Menu Wednesday.
Recipe from Reynolds Wrap
Thursday, February 4, 2010
Teriyaki Pork Chops
Posted by Stacy at 9:21 AM
1 comments:
- Jane said...
Oh...that sounds good! :)
- February 7, 2010 at 4:48 PM
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