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the tablet looks similar to a vicodin m 357, only it is smaller. it has a line across the middle of one side as the m357 does and 126 imprinted on the other.
What is this pill - with '126' imprint?
- Posted:
- 18 Sep 2009 by mandiegom7
- Topics:
- vicodin
Answers (1)
27 Apr 2012
Pill imprint 126 has been identified as Acetaminophen and hydrocodone bitartrate 325 mg / 5 mg (generic Vicodin).
Further Information
- Vicodin Information for Consumers
- Vicodin Information for Healthcare Professionals (includes dosage details)
- Side Effects of Vicodin (detailed)
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Hedgesville Vacation Packages
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300 Clinton Avenue
Plainfield, New Jersey, 07063
Commute to Downtown North Plainfield
Some errands can be accomplished on foot.
About your score
300 Clinton Avenue has a Walk Score of 69 out of 100. This location is Somewhat Walkable so some errands can be accomplished on foot.
This location is in Plainfield. Nearby parks include Green Brook Park, Walnut Park and Columbia Park.
Explore how far you can travel by car, bus, bike and foot from 300 Clinton Avenue.
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1.2 mi
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This location is in the city of Plainfield, NJ. Plainfield has an average Walk Score of 59 and has 49,808 residents.Learn More About Plainfield


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swhite83 posted a topic in Ford Fiesta ClubHi Guys Im new on here so hopefully some of you will be able to help me. I have a 58 plate fiesta zetec. On the little mileage screen that displays how many miles you have left until you need to fill up, mine has changed to show me how many miles per gallon im doing. I havent touched anything, and dont want it to show me this, id rather know how many miles i have left until i break down! Anyone know how to change this back? Thank you all in advance :-)


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The molecular basis for psychosocial-distress mediated immune-dysregulation is not well understood. The purpose of this study was to determine whether peripheral blood mononuclear cell (PBMC) epigenetic pattern associates with this form of immune dysregulation. Women newly diagnosed with early stage breast cancer were enrolled into the study and psychosocial, immunological and epigenetic assessments were made at diagnosis and four months later, after completion of cancer treatment. At diagnosis women reported increased perceived stress, anxiety, and mood disturbance and the PBMC of these women exhibited reduced natural killer cell activity and reduced production of interferon gamma, which contrasted with results, obtained after completion of treatment. At the epigenetic level, a PBMC subset derived from women at diagnosis exhibited a distinct epigenetic pattern, with reduced nuclear acetylation of histone residues H4-K8 and H4-K12, as well as reduced phosphorylation of H3-S10, when compared to similar cells derived after the completion of treatment. Natural killer cell activity and interferon-gamma production were associated with nuclear acetylation and phosphorylation status of these histone residues. These findings demonstrate associations among nuclear epigenetic pattern and the immune dysregulation that accompanies psychosocial distress.
A diagnosis of breast cancer and the challenge of cancer treatment can be emotionally devastating and are often accompanied by elevations in perceived stress, anxiety and mood disturbance (National Cancer Institute, 1997; Witek-Janusek et al., 2007; Shapiro et al., 2001). Ample evidence demonstrates that psychosocial distress negatively impacts immune function (Witek-Janusek and Mathews, 2000; Kemeny and Schedlowski, 2007; Glaser and Kiecolt-Glaser, 2005; Segerstrom and Miller, 2004). The impact on immune function has been demonstrated to include reductions in natural killer cell activity (NKCA) (Biondi, 2001; Kiecolt-Glaser et al., 1987; Witek-Janusek et al., 2007; Witek-Janusek et al., 2008), alteration of cytokine production (Maes et al., 1999; Marshall et al., 1998; Witek-Janusek et al., 2007; Esterling et al., 1994; Witek-Janusek et al., 2008), decreased PBMC proliferative response to mitogens (Kiecolt-Glaser et al., 1991; Andersen et al., 1998; Andersen et al., 2004), reductions in specific B- and T-lymphocyte mediated immune responses (Kiecolt-Glaser et al., 1996), decreased production of interferon (IFN) gamma (Witek-Janusek et al., 2007; Glaser et al., 1986; Larson et al., 2000), and diminished NK cell response to cytokines (Andersen et al., 1998; Fawzy et al., 1990).
Stress-related impairment of immune function is evident in women with breast cancer. For example, we have previously reported that women undergoing breast cancer diagnosis and treatment exhibit increased anxiety and mood disturbance, accompanied by reduced NKCA and reduced production of IFN gamma (Witek-Janusek et al., 2007; Witek-Janusek et al., 2008). Others have shown that among women with breast cancer, those who report greater subjective distress after their breast cancer surgery have lower basal and IFN augmented NKCA and reduced T cell proliferative responses to mitogens (Andersen et al., 1998; Andersen et al., 2004). Because NK cells and IFN gamma could potentially contribute to surveillance and destruction of tumor cells (Dighe et al., 1994; Kagi et al., 1994; Kaplan et al., 1998; Smyth et al., 1998; Smyth et al., 1999; Street et al., 2001; Van Den Broek et al., 1996; Seki et al., 2003; Smyth et al., 2005; Wallace and Smyth, 2005), stress-induced immune dysregulation may jeopardize cancer control, especially during vulnerable period such as during and immediately post-treatment (Lutgendorf et al., 2007; Avraham and Ben-Eliyahu, 2007).
The molecular basis for the effects of psychosocial distress on immune function, relevant to cancer control, is unclear. For early stage breast cancer patients, a tumor is removed from the breast and the primary site and adjacent tissues are irradiated. These procedures are thought to eliminate any nascent tumor cells. Prognosis is good, but the disease can recur after apparent successful eradication of the tumor. Recurrence occurs in some women but not in others. The reasons for this disparity in recurrence are not known and are certainly multiple. However, it is possible that psychosocial distress mediated immune-dysregulation is a contributing factor. Therefore, explicating the molecular basis for this immune-dysregulation is a significant objective. One unexplored possibility is that psychosocial distress induces epigenetic modifications that alter transcription of relevant immune effector genes. Post translational modifications, regulate chromatin accessibility through modification of histone residues, which can limit production of immune effector molecules necessary to optimal immune function (Krukowski et al., 2010,Krukowski et al., in press). A series of studies have demonstrated epigenetic modifications to be responsive to environmental stimuli (Zhang and Meaney, 2010) and evidence demonstrates that psychological stressors result in epigenetic modification, which modify or impact glucocorticoid response pathways (Bilang-Bleuel et al., 2005; Chandramohan et al., 2007; Chandramohan et al., 2008). Psychosocial distress activates the hypothalamic-pituitary-adrenocortical (HPA) axis resulting in elevations in circulating levels of glucocorticoids that have strong immuno-modulatory effect. It is possible that stress-induced elevations in glucocorticoids (Chrousos and Gold, 1992; Chrousos, 2000) may mediate the immune dysregulation observed in women with breast cancer through epigenetic modifications.
Indeed, we have shown that a diagnosis of breast cancer is accompanied by elevations in plasma cortisol that persist over several months (Witek-Janusek et al., 2007; Witek-Janusek et al., 2008). Glucocorticoid can produce deacetylation of histones with reduced expression of immune response genes (Barnes, 1998; Kagoshima et al., 2003). This effect has been demonstrated with deacetylation of lysine residues of histone H4K-8 and K-12, resulting in suppressed gene transcription, including reduced NKCA and IFN gamma production (Krukowski et al., 2010,Krukowski et al., in press). Such deacetylation results in epigenetic repression of the associated genes (Kagoshima et al., 2001; Mishra et al., 2001). It is possible that similar epigenetic effects may mediate the effects of psychosocial distress on immune function. Hence, this study evaluated the epigenetic pattern of the PBMC of women experiencing psychosocial distress, as a consequence of breast cancer diagnosis, and compared that to the epigenetic pattern of the PBMC of women at a time after treatment, when the psychosocial response to cancer had dissipated and immune function had been improved. As such, the purpose of this study was to evaluate associations among epigenetic patterns and immune function during a period of psychosocial distress. In this study that period was designated P1.
Thirty-three women (35–75 years of age) diagnosed with early stage breast cancer, who had breast conserving surgery and did not receive systemic chemotherapy, but whose treatment did include radiotherapy, participated in this study. These women were all diagnosed with stage 0 ductal carcinoma in situ (DCIS) and all had small lesions (< 1 cm) and uninvolved axillary lymph nodes. Women were excluded if they had an immune-based disease, were incapable of reading and writing English, were diagnosed with immune-based disorders, psychoses, anxiety disorders or cognitive impairments, were substance abusers, had a history of acute infection or were taking corticosteroids. The demographic characteristics of these women are described in Table 1. This study was approved by the Loyola University Medical Center Institutional Review Board for the Study of Human Subjects. All procedures were carried out with the adequate understanding and written consent of the subjects.
Eligible women were identified in association with clinic physicians after completion of their breast surgery and when their full surgical pathology report was available and diagnosis and treatment plans were complete. Interested women were met by research clinical associates at a scheduled clinic visit. The purpose and nature of the study was further described and those willing to participate were consented. Data were collected at 3–4 weeks after the final cancer diagnosis was made (referred to as P1), which was 10–12 days post breast surgery and before any adjuvant therapy (i.e., radiotherapy) was initiated. This time period has been shown previously to a period of elevated anxiety, mood disturbance and perceived stress as well as immune dysregulation (Witek-Janusek et al., 2007). Data were collected as well approximately 4 months after P1, which was 2 months after the completion of radiotherapy (referred to as P2). This time period has been shown previously to be a period of reduced psychosocial distress and normalized immune function, similar to that of cancer free women (Witek-Janusek et al., 2007).
For the purposes of this study the psychosocial distress associated with breast cancer was conceptualized as a state evoked by an event appraised as a threat to the individual's well-being, which, in turn, led to feelings of anxiety and mood disturbance. With this in mind, the psychosocial assessment of these women included measurement of perceived stress (Perceived Stress Scale), mood state (Profile of Mood States) and anxiety (State-Trait Anxiety Inventory).
The PSS is a 10-item scale that provides a general appraisal index of stress (Monroe and Kelley, 1995). It measures the degree to which experiences are appraised as uncontrollable. For the PSS women were instructed to rate their degree of perceived stress over the past month. Internal consistency is good with coefficient alphas ranging from 0.75–0.86. Test-retest reliability has been reported to be 0.85 (Cohen and Williamson, 1988).
The POMS is a 65-item measure designed to identify and assess general distress/mood. A total mood score was obtained. Women were asked to indicate the extent to which each of the scale's 65 adjectives of mood describe the way they had been feeling during the past week, on a scale ranging from 0 (not at all) to 4 (extremely). A total mood disturbance score is derived by summing each of the six subscales, with vigor weighted negatively. The possible range of scores is −40 through 192. Internal consistency alphas range from 0.87–0.95, and stability coefficients (test-retest) are 0.65–0.74 (Mcnair et al., 1992).
The State-Trait Anxiety Inventory is a 40-item self-report measure of state and trait anxiety. Only the state anxiety inventory was used in this study. The State-Trait Anxiety Inventory has alpha reliability coefficients of 0.83–0.92 and convergent validity with other anxiety tools (alpha =0.75–0.80) (Spielberger et al., 1970). The State-Trait Anxiety Inventory has been used to discriminate anxiety in women with benign versus malignant breast biopsy findings (Sachs et al., 1995).
Blood was collected in sterile heparinized tubes and processed immediately. Heparinized peripheral blood was overlaid onto Ficoll/Hypaque and centrifuged at 1,000 x g for 20 min. The peripheral blood mononuclear cells (PBMC) at the interface were washed twice with Hank's Balanced Salt Solution prior to assessment of NKCA, cytokine production, or phenotypic analysis. Phenotypic analysis was as described previously (Nagabhushan et al., 2001). Briefly, isolated PBMCs were analyzed with specific fluorochrome conjugated antibodies (BD Biosciences, San Jose, CA) in order to identify specific subsets of PBMCs including: CD3 for T lymphocytes, CD56 for NK cells; CD3 and CD56 for NKT cells; CD4 for helper lymphocytes; CD8 for cytotoxic lymphocytes, and CD14 single positive cells were identified as circulating monocytes. Semi-quantitative analysis of the phenotypic expression of relevant leukocyte surface molecules was determined by immunofluorescence using a FACS Star Plus System. Interassay variability for PBMC laboratory values ranged from 1.5 – 7.9%. Essentially all women completed these psychosocial assessments, but not all immune assays were completed for all women due to limitations with regard to total volume of blood obtained for a particular assessment period.
K562 tumor cells, obtained from the American Type Culture Collection, Rockville, MD, were radioactively labeled with 100 uCi of [51Cr] (New England Nuclear, Boston, MA). Radiolabled K562 cells were incubated for 4 hr with PBMC. Following incubation the supernatants were removed using a Skatron harvesting press (Skatron Inc., Sterling, VA) and the associated radioactivity was determined. E:T ratios for NKCA were 50, 25, 12 and 6:1.
Results are expressed as % cytotoxicity and calculated by the formula:
All experimental means were calculated from triplicate values. Lytic units (LU) were calculated by a program written by David Coggins, FCRC, Frederick, MD and represents the number of cells per 107 effectors required to achieve 20% lysis of the targets. *DPM=disintegrations per minute.
Interferon (IFN) gamma was measured under optimal conditions in bulk PBMC culture supernatant fluids as described previously (Witek-Janusek and Mathews, 1999). Briefly, PBMC (1 × 106 cells/ml) were cultured with and without PMA/PHA (PMA @ 20 ng/well; PHA @ 0.05%/well) in 24 well plates for 48 hr at 37° C. Aliquots of the culture supernatants were stored at –80° C for subsequent cytokine analysis.
IFN gamma was measured using quantitative sandwich enzyme immunoassay (Quantikine kits, R & D Systems). Sensitivity for IFN gamma was <3 pg/ml. Coefficient of variation was 2.6%.
PBMC (1.0 × 105/assessment) were fixed and permeabilized with Cytofix/Cytoperm solution (BD Pharmingen, San Jose, CA) for 20 min at 4°C. The cells were then washed twice with Perm/Wash Buffer (BD Biosciences, San Jose, CA) and then probed with antibodies specific for molecules of interest. The antibodies used were anti-acetyl-histone H4-K8 (H4-K8 Ac) (Millipore, Temecula, CA) (unconjugated); anti-acetyl-histone H4-K12 (H4-K12 Ac) (Millipore, Temecula, CA) (unconjugated); anti-phospho-histone H3-S10 (H3-S10 PO4) (Alexa Fluor 488 conjugated) (Cell Signaling, Danvers, MA). Isotype matched control antibody (mouse IgG1, IgG2b or rabbit IgG; BD Bioscience, San Jose, CA & Millipore, Temecula, CA) were used to ensure specificity. The cells were then washed twice with Perm/Wash Buffer (BD Biosciences, San Jose, CA), after which, secondary anti-IgG (FITC conjugated) (Millipore, Temecula, CA) was added for 1 hr at 4°C as appropriate. The cells were then washed twice with Perm/Wash Buffer (BD Biosciences, San Jose, CA) resuspended in 0.1% BSA (Sigma Aldrich, St. Louis, MO) in PBS (Gibco, Grand Island, NY). For intracellular cytokine analysis of IFN gamma, cells were incubated in leukocyte activation cocktail (BD Bioscience, San Jose, CA) at 37°C for 3 hrs prior to permeabilization and antibody staining. Cells were then permeabilized and incubated with PE conjugated antibodies specific for IFN gamma (BD Bioscience, San Jose, CA) for 1 hr at 4°C as well as with antibodies specific for individual surface molecules. Cells were then washed twice with 0.1% BSA (Sigma Aldrich, St. Louis, MO) in PBS (Gibco, Grand Island, NY) and resuspended in 1% paraformaldehyde (PFA) (Sigma Aldrich, St. Louis, MO). Samples were analyzed with a FACSCanto Fluorescence-Activated Cell Sorter equipped with a 15mW argon-ion laser and a red diode laser using FACSDiva software for data acquisition (Beno et al., 1995; Yamamura et al., 1995; Nagabhushan et al., 2001). After staining, cells were analyzed by flow cytometry. 10,000–30,000 events were recorded and analyzed with FlowJo v8.4.1. Fluorescent activated cell sorting was used to isolate individual cell populations in order to confirm flow cytometric analysis by microscopy. Individual cell populations were analyzed by immunofluorescent microscopy and/or by confocal immunofluorescent microscopy. Nuclei were identified by staining with 4 μg/ml 4′,6-diamidino-2-phenylindole (DAPI) for 10 min.
Data are expressed as means with the standard error of the mean (SEM). Missing data were treated as such and no imputation techniques were used. A two-sided alpha of 0.05 was set for statistical significance. Comparison of data (P1) to 4 months later (P2) was by paired t test, two tailed. Associations were examined by Pearson's correlation coefficient and an alpha of p < 0.05 was applied. The Statistical Package for Social Sciences (SPSS: version 15.0) was used for data analysis.
Table 2 illustrates the mean scores for anxiety, mood disturbance and perceived stress of women 3–4 weeks after cancer diagnosis (referred to as P1) and 2 months after the completion of radiotherapy and approximately 4 months after enrollment (referred to as P2). Total mood disturbance (POMS-TMD), state anxiety (STAI) and perceived stress (PSS) were significantly elevated at P1 for women diagnosed with breast cancer, when compared to P2.
Natural killer cell activity (NKCA) is presented in Table 3 along with PBMC production of IFN gamma. At P1 NKCA and IFN gamma production were significantly reduced when compared to P2. Analysis of circulating PBMC subset number and percentage showed no difference between P1 and P2. Furthermore, there was no difference in the numbers of circulating CD56 bright or dim NK cells.
The epigenetic pattern, as global mean fluorescence intensity (MFI) for CD56+ lymphocytes derived from these women, is presented in Table 4. A reduction in the acetylated forms of H4-K8 and H4-K12 was demonstrated at P1 compared to P2. A numerical reduction in phosphorylated H3-S10 was observed at P1 compared to P2.
No correlation was found among epigenetic pattern and psychosocial measures. However, correlations were found to be significant for the PSS and immune values at P1. Scores for the PSS demonstrated correlation with NKCA ( r = −0.344, p = 0.043) and with IFN gamma production ( r = −0.478, p = 0.021). (No other psychosocial measure demonstrated significant correlation with immune values.) However, based on these observations, examples of flow cytometric patterns of PBMC derived from women with a spectrum of perceived stress scores were selected. In Figure 1, individual examples of flow cytometric epigenetic patterns for nuclear fluorescence of H4-K8 Ac of CD56+ lymphocytes are depicted. In panel (a) the histogram of cellular fluorescence is depicted for a woman with a high perceived stress score (global MFI = 1,549). In panel (b) the histogram of cellular fluorescence is depicted for a woman with an intermediate level of perceived stress (global MFI = 4,504) and in panel (c) the histogram of cellular fluorescence is depicted for a woman with a low perceived stress score (global MFI = 6,328). Panel (d) superimposes the three histograms.
It is apparent that these histograms have two peaks of immunofluorescence, with a shift from the higher intensity peak to the lower intensity peaks with increased perceived stress. Global H4-K12 Ac and H3-S10 P04 flow cytometric epigenetic analysis of the same examples of CD56+ lymphocytes is presented in Figure 2. In each case the least MFI was demonstrable with the greatest degree of perceived stress. For global H4-K12 Ac (Figure 2A) the pattern for women with the greatest degree of perceived stress is represented by pattern (a) (global MFI = 1,499), an intermediate level of perceived stress by pattern (b) (global MFI = 4,043) and the least perceived stress by pattern (c) (global MFI = 8,245). For global H3-S10 PO4 (Figure 2B) the pattern for women with the greatest degree of perceived stress is represented by pattern (a) (global MFI = 280), an intermediate level of perceived stress by pattern (b) (global MFI = 2112) and the least perceived stress by pattern (c) (global MFI = 7,416). A comparison of fluorescently stained nuclei of these PBMCs is depicted in Figure 3. Figure 3a and c depict the fluorescence microscopic appearance of CD56+ lymphocyte nuclei derived from a woman with low perceived stress and high MFI. Figure 3b and d depict CD56+ lymphocyte nuclei from a woman with high perceived stress and a low MFI. The immunofluorescent microscopic images demonstrate the fluorescence to be primarily within the nuclei of the cell in Figure 3a, with little or no fluorescence detected in Figure 3b. The confocal microscopic images demonstrate that the fluorescence of the nuclei is distributed throughout the central z plane of the nuclei, Figure 3c compared to Figure 3d. Similar results were obtained with anti- H4K8 AC and anti-H3S10 PO4. Data are not shown. Other histone residues as well have been evaluated for the CD56+ lymphocytes including; acetylated H3-K9, H3-K14, H4-K5, H4-K16 and no differential effect was found when comparing the nuclear staining of PBMCs derived from women with and without perceived stress. In some cases nuclear staining was demonstrable for both groups of women at an equivalent level (i.e. H4-K5 and H4-K16). In other cases no staining of the nuclei was observed (i.e.. H3-K9 and H3-K14). In all cases, similar primary, secondary and isotype control antibodies were employed ensuring that the capacity to stain the nuclei was equivalent and specific.
NKCA is carried out exclusively by CD56+ lymphocytes while IFN gamma production can be by CD4+ and CD8+ T lymphocytes as well as CD56+ lymphocytes. Comparison of the percentage of CD56+ lymphocytes producing intracellular IFN gamma showed a difference P1 to (9.6 + 5.2 % CD56+ IFN gamma+) to P2 (17.5 + 9.4 % CD56+ IFN gamma+), t = −3.298, df = 21, p = 0.002, while no difference was observed P1 to P2 for intracellular IFN gamma for either the CD4+ or CD8+ lymphocyte populations (p > 0.05).
Correlations were explored among the immunological variables and the histone epigenetic marks at P1 as judged by global MFI. Three epigenetic marks were evaluated for NKCA and the same three were evaluated for IFN gamma production. See Table 5. Phosphorylation of H3-S10 and acetylation of H4 residues K8 and K12 were correlated with NKCA and with IFN gamma production. No correlations among these variables were observed at P2 when psychosocial distress was reduced and immune function was increased.
Given the pervasiveness of psychosocial distress in society, and the importance of the immune system to health, explicating the molecular mechanisms by which distress disrupts immune function may have implications for cancer patients. For the women assessed by this study, total mood disturbance, state anxiety and perceived stress were significantly elevated at P1 when compared to P2. The elevated anxiety, mood disturbance and perceived stress at P1 were similar to that of a group of women who completed similar analysis at the time of breast cancer diagnosis (Witek-Janusek et al., 2007). In that study and in this, NKCA and IFN gamma production by PBMC (at P1) were significantly reduced when compared to a time period 2 months after the completion of radiotherapy (P2). Analysis of circulating PBMC subset number and percentage showed no difference between P1 and P2 and suggests that the reduction in NKCA and in IFN gamma was an actual reduction in functional activity and not in circulating PBMC subset numbers. Significantly, this immune dysregulation was accompanied by reductions in nuclear acetylated H4-K8 and H4-K12 derived at P1. For the PBMC subset analyzed, significant correlations were found among immune functional activity and the acetylation of H4 residues K8 and K12 and the phosphorylation of H3-S10. In comparison to P1, increased immune functional activity and significantly increased nuclear acetylation of H4-K8 and H4-K12 and increased phosphorylation of H3-S10 was observed at P2. These data suggest associations among nuclear epigenetic pattern and the immune effects that accompany psychosocial distress.
Epigenetics refers to a variety of processes that affect gene expression independent of actual DNA sequence. Most importantly, recent evidence demonstrates that epigenetic information is susceptible to change in response to environmental stimuli, including behavior and stressful experiences. For example, a variety of animal models of psychosocial stress, such as chronic social defeat (Tsankova et al., 2006; Wilkinson et al., 2009), social isolation (Wilkinson et al., 2009), forced swimming and rodent exposure to predators (Bilang-Bleuel et al., 2005) document that epigenetic modification are dynamic and responsive to adverse environmental events and, furthermore, that such modification relate to anxiety-like behaviors and depression (Tsankova et al., 2006; Wilkinson et al., 2009). Differential effects have also been demonstrated for acute versus chronic restraint stress (Hunter et al., 2009), which substantiate that stress-elicited epigenetic modifications can occur rapidly, and are sensitive to stressor duration (Hunter et al., 2009). Although the vast majority of stress-induced chromatin remodeling has been demonstrated in the brain, those studies are relevant to this in that collectively the data reported in those studies indicate that epigenetic modification contributes to the overall adaptive response to stress. However, there is scant evidence that psychosocial distress, maladaptive behaviors or emotions, produce epigenetic modifications that impact immune function; even though significant literature links each of these. However, evidence does exist that epigenetic pattern influences differentiation of T and B-lymphocytes as well as the fate and function of individual immune cell populations (Cuddapah et al., 2010; Martino and Prescott, 2010). Further, PBMC derived from individuals with post traumatic stress disorder (PTSD) have been demonstrated to exhibit differential epigenetic modification of genes that encode for immune effector function, when compared to PBMC derived from individuals without PTSD. The affected genes were significantly and negatively correlated with traumatic burden (i.e., number of traumatic event exposure). Moreover, the unique modification was also associated with differences in immune responsiveness to cytomegalovirus, a latent herpes virus. These results imply that immune dysfunction observed in those with PTSD is related to epigenetic pattern (Wrona, 2006). We have shown previously that the psychosocial distress of breast cancer diagnosis is associated with reduced immune function (Witek-Janusek et al., 2007; Witek-Janusek et al., 2008) and the data presented herein show an association with epigenetic modification of circulating immune cells.
It is important to note that the underlying cell and molecular mechanisms by which psychosocial distress adversely affects the immune system are unclear. However, functional genomic analyses have demonstrated alterations in the expression of genes regulated by the glucocorticoid receptor (GR) and NFkB in the PBMC of individuals experiencing prolonged chronic stressors or social isolation, with significant modification of glucocorticoid response element (GRE) mediated transcriptional activity (Miller et al., 2008; Cole et al., 2007). The modification of GRE mediated transcriptional activity was not explained by GR mRNA levels and the mechanistic basis for those observations remains unclear. However, one possible explanation is that the reduction relates to the transactional effects of GR recruitment of enzymes that modify acetylation and/or phosphorylation of histone residues, essential to promoter region transcriptional activity. The data reported herein suggest that epigenetic modification of immune cells may underlie immune effects observed in women responding to the stressful experience of breast cancer diagnosis.
Women enrolled into this study had data collected 3–4 weeks after cancer diagnosis and 10–12 days post breast surgery (referred to as P1). An interval of 10–12 days after surgery provides a time period in which ample evidence shows that the effects of surgery, anesthesia and analgesia, on immune function, dissipate (Whelan et al., 2003; Wichmann et al., 2003; Mokart et al., 2002; Decker et al., 1996; Koda et al., 1997; Kutza et al., 1997; Pollock et al., 1991; Koltun et al., 1996; Shakhar and Ben-Eliyahu, 2003; Spies et al., 2004; Homburger and Meiler, 2006). These women were not confounded by the effect of metastatic or advanced breast cancer nor did they receive adjuvant therapy. As such, this subject sample was well suited for the analysis of the molecular mechanisms whereby psychosocial distress affects immune function. Data were collected as well 4 months after P1, which was 2 months after the completion of radiotherapy (referred to as P2). At this time period the women, as a group, showed a quantitative reduction in psychosocial distress and increased immune function.
For non-housekeeping genes, transcriptional activation through sequence-specific DNA-binding proteins can localize histone acetyltransferases or phosphorylases (Henikoff and Ahmad, 2005; Lieb and Clarke, 2005; Reinke and Horz, 2003). These enzymes modify histone residues, which then adapt the promoter regions for transcription. These histone acetyl and phosphate groups are present while transcription is active and removed when transcription is no longer active. These acetylated histone residues act as epigenetic marks for transcription (Govind et al., 2007). Such transient epigenetic change has been described for the T lymphocyte IL-2 locus (Thomas et al., 2005). Genomic DNA spanning the 700-bp region upstream of the transcriptional start site for the IL-2 gene is completely inaccessible in naïve T lymphocytes, indicating that the IL-2 locus in these cells exists in a highly compact and condensed chromatin structure. Following cellular activation, the entire upstream region became accessible, suggesting that the chromatin encompassing the entire IL-2 promoter/enhancer in these effector cells was de-condensed and wrapped loosely around free nucleosomes. The genomic region remained accessible to DNA binding proteins during IL-2 transcription. When these T lymphocytes were allowed to come to rest, that is when the activation signal was interrupted, the entire probed region upstream of the IL-2 gene returned to an inaccessible configuration similar to that in naive T lymphocytes. These observations demonstrate the dynamic nature of chromatin structure at the IL-2 promoter/enhancer and upstream regions, as well as their susceptibility to kinetic variation and effects of histone acetylation and DNA demethylation (Thomas et al., 2005). That study was accomplished in vitro and this study was accomplished with cells derived from peripheral blood over a 4-month period. The differences between the two studies are obvious, but the data reported herein are consistent with that previously published in vitro work. The results of this study do indicate relationships among epigenetic pattern and immune functional activity. However, the means by which epigenetic pattern is modified during psychosocial distress has not been established. However, it is well established that cortisol levels are dysregulated in women diagnosed with breast cancer, who exhibit psychosocial-distress, mood disturbance, and immune-dysregulation (Witek-Janusek et al., 2008). Cortisol acts by binding to cytosolic GR, which can suppress gene transcription by direct interaction with the coactivator, cyclic AMP response-element-binding protein-binding protein (CBP). This interaction inhibits CBP-associated histone acetyltransferase activity resulting in the active recruitment of histone deacetylase (Ito et al., 2000; Matthews et al., 2004; Tsaprouni et al., 2002; Espada and Esteller, 2007; Ito et al., 2006) and dephosphorylation complexes (Parra et al., 2007; Kim et al., 2008). Deacetylation and dephosphorylation lead to chromatin modification, resulting in immune dysregulation (Kagoshima et al., 2001; Mishra et al., 2001; Plesko et al., 1983). Epigenetic patterns have been shown to regulate IFN gamma production (Avni et al., 2002; Muegge et al., 2003; Mishra et al., 2001; Parra et al., 2007; Kim et al., 2008) as well as molecules that contribute to NKCA (e.g. perforin) (Krukowski et al., 2010,Krukowski et al., in press; Lu et al., 2003; Babichuk et al., 1996) and glucocorticoids are known to decrease PBMC NKCA and IFN gamma production (Mishra et al., 2001; Barnes, 1995; Witek-Janusek and Mathews, 2000; Biondi, 2001; Cippitelli et al., 1995). Reductions in PBMC NKCA and IFN gamma production may therefore be a direct consequence of epigenetic patterns influenced by exposure to cortisol, as a consequence of HPA activation (resultant from psychosocial distress). If so, then the distinctive epigenetic pattern detected in the PBMC of women who experience psychosocial distress may be a consequence of these altered cortisol levels. Most women do report emotional distress at diagnosis and most women exhibit recovery from the initial distress of breast cancer diagnosis. Reductions in perceived stress, anxiety and mood disturbance were demonstrated at P2 compared to P1 in this study and have been demonstrated in other similar investigations during such time periods (Thornton et al., 2007; Edgar et al., 1992; Ganz et al., 1996). When psychosocial distress is reduced, cortisol levels would normalize and restore immune function (Thornton et al., 2007). Although not proven in this investigation it is possible that the observed PBMC epigenetic patterns are subsequent to changes in circulating cortisol levels. It has been shown that a synthetic glucocorticoid, dexamethasone, does induce similar immune and epigenetic effects in immune cells (Krukowski et al., 2010,Krukowski et al., in press), and it may be that the distinct PBMC epigenetic patterns observed during psychosocial distress may be similarly modified by cortisol levels in response to stress-induced activation of the HPA axis.
It is acknowledged that other histone post-translational modifications exist. The number of these is quite large. For example, acetylation of H3-K9, H3-K14, H4-K5 and H4-K16 as well as methylation modifications of H3-K4 and/or H3-K9 (mono-, di- and tri-methylation) have been described and may contribute to chromatin accessibility (Schotta et al., 2004; Bjornsson et al., 2004; Shahbazian and Grunstein, 2007). Many of these histone modifications have been evaluated in the context of cell types other than human PBMC. It was not the purpose of this study to survey all such modifications, but it is worth nothing that H4-K8 and H4-K12 have been demonstrated to be hypo-acetylated in glucocorticoid treated cell populations, including PBMC (Ito et al., 2000; Matthews et al., 2004; Tsaprouni et al., 2002) and that H3-S10 phosphorylation has been associated with opening of condensed and transcriptionally active chromatin (Saccani et al., 2002; Arbibe et al., 2007). Those results are fully consistent with the observed correlations among immune function, acetylation and phosphorylation of histone residues described herein and the fact that accessible promoter regions for genes encoding immune effector molecules are necessary for optimal immune response (Krukowski et al., 2010,Krukowski et al., in press).
There are limitations to this study. Women were enrolled into the study after the diagnosis of breast cancer. As such there is no baseline data for these women. In addition, the design of the study is temporal and over a 4 month period. This design permits a comparison of the women at two separate time periods but does not permit a comparison to actual baseline values or to a non-cancer group of women. Further, the women were treated for breast cancer by radiotherapy and that treatment may have effect upon P2 outcomes, even though the women received localized radiotherapy, which was completed 2 months prior to P2. Another limitation of this study is that analysis was accomplished with whole PBMC. That is, batch preparations of PBMC were analyzed for nuclear epigenetic pattern and immune function. This approach allowed for the identification of associations among the measured aspects of epigenetic pattern and immune function, but did not allow for a correlation of epigenetic pattern and reduced immune function at the level of the individual cell. That is, no direct evidence indicates that an individual cell with a particular demonstrable epigenetic pattern also had a demonstrable modification in its immune functional capacity (e.g. a change in levels of intracellular IFN gamma). Epigenetic pattern and immune function were correlated for a PBMC subset as a whole, but the observed changes may represent a summation of the entire PBMC subset and may not be a consequence of a unique change within an individual cell.
The effect of psychosocial distress on epigenetic pattern and functional activity of human peripheral blood cells is demonstrated.
Individual epigenetic histone marks that are affected by psychosocial distress are identified.
Associations among individual epigenetic histone marks and functional immune activity are demonstrated.
The study was supported in part by the National Cancer Institute R21-CA–117261, R01-CA-134736 and the Research Committee of the Council, Stritch School of Medicine. The authors gratefully acknowledge the expertise of Patricia Simms Loyola University Health Systems Flow Cytometry Facility and the assistance of Valerie Bednar, RN, MSN and Jennie Johnson, RN for recruitment of subjects and collection of clinical and psychological data. Importantly, the authors express sincere gratitude to those women with breast cancer who volunteered to participate in this study.
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Skip to comments.WATCH: Iowa GOP Senate Candidate Still Believes There Were Weapons of Mass Destruction in Iraq
Posted on 05/12/2014 6:06:11 PM PDT by 2ndDivisionVet
War veteran Joni Ernst claims to have vague, secret knowledge that contradicts every public report.
Iowa state senator and US Senate candidate Joni Ernst captured national attention when her campaign's first TV ad featured the candidate talking about castrating hogs (a subsequent ad featured Ernst at a gun range, implying that she'd shoot Obamacare to bits). But if the Sarah Palin-approved Republican wants to enter national politics, she may need to brush up on some of her facts. Ernst still thinks Saddam Hussein possessed weapons of mass destruction when the US invaded Iraq, despite all evidence pointing to the contrary.
On Friday, Ernst sat down with the Des Moines Register's editorial board for a wide-ranging interview. Ernst served in the Iraq War in 2003, "running convoys through Kuwait and into southern Iraq" according to her campaign website. She defended that war during the interview, saying that the intelligence at the time offered compelling reason to displace Saddam. "Obviously the president thought there was actionable intelligence, she said, "so as an Iraqi War veteran I stand beside that and I'll stand beside every other soldier I served with in believing we were on a clearly defined mission to go into Iraq." (Her response in the video above starts at the 23:20 mark.)
Why is Ernst so willing to support Bush's decision to invade? She hints that she has inside knowledge that there were, indeed, still weapons of mass destruction when the war began. "We don't know that there were weapons on the ground when we went in," she said, "however, I do have reason to believe there were weapons of mass destruction in Iraq." When a Register reporter quizzed her on what information she has, Ernst said "my husband served in Saudi Arabia as the Army Central Command sergeant major for a year and that's a hot-button topic in that area."
Of course, US troops never managed to find any such weapons after the invasion. George W. Bush, Dick Cheney, and Donald Rumsfeld have all conceded that the initial intelligence was flawed.
When asked for clarification, a spokesperson for Ernst's campaign narrowly walked back her comments over e-mail: "Her point was that we know for a fact that Iraq had chemical weapons in the past, and had even used them. We also know none were found while our troops were on the ground, despite the intelligence at the time. What happened to those weapons she doesn't know."
Ernst currently holds a slight lead in the polls in advance of the June 3 primary. If she managed to win the general electionDemocrat Bruce Braley is the front-runner for the open seatErnst would be the first woman elected to federal office from Iowa.
The left keeps on saying there were no WMD's in Iraq..so I have a simple question for leftists..where did Assad get those same weapons that he has been using on his own people..did they come out of his butt?
It's not a great comment to make on the campaign trail, even though she couched it well. Though, there is some element of truth to this. Wasn't there a well-evidenced theory about them being moved? I think Niger was involved, or maybe Assad. Also, if WMDs include chemo-weapons we know he had those at one point.
Ernst seems like a good candidate and she'd be a vast improvement upon the gargoyle she's trying to replace. Let's hope she beats Braley
(P.S - to the Karl Rove shills on their way, don't bother making fools out of yourselves again)
Where do these shepherdless sheep think Assad's WMD's came from? Sheesh.
Of course they did. Just ignore all the plane flights and truck convoys moving from Iraq to Syria before the invasion. They were delivering aspirin, yeah that's the ticket.
They believed the WMDs when Clinton was President.....http://www.snopes.com/politics/war/wmdquotes.asp
The Russians came in to move the weapons into Syria before the war.
MoJo knows this, as do most hard-core totalitarian American communists.
Maybe because there were WMD's in Iraq. Get over it lefties, you are retarded and liars.
Deadly chemicals are found dumped in river
Evidence of WMDs in Iraq - Annonymous Freeper in Iraq
Cyanide Salt Block Found in Iraq
MSNBC - Cyanide & Mustard Agents Found in Euphrates River
NBC Forces Out Bob Arnot Who Delivered Upbeat Stories from Iraq(Arnot Charges Bias)
Of course there were. What'd they gas the Kurds with? Nitrous oxide?
I agree with her. I believe they were taken to Syria. I remember there being news or information of large convoys going out of Iraq in the middle of the night for quite some time prior to the war.
That's what I have thought up to and including now. I don't know why Bush et al capitulated.
To a person out of (now) 72 comments, they were denigrating and snickering at her on the Quad City Times.
As did England, Germany, France, etc. They were there. We found stuff that W decided just not to inform the public of. Probabaly a smart move. Don't let our enemies know what we know.
What did get in the press was uranium (enriched I don't know), Sarin going to Syria and used in an failed attack in Lebanon, lots of mobile labs and processing centers, other places gutted. Basically the report that coward Colin Powell showed at the UN and now whines about.
But the reality and bottom line was Iraq had continued to violate the cease-fire agreement and after 9/11 it was time to quit being a pussy about it like Clinton.
I'm getting more than fed up with bystanders whining that some candidate shouldn't have a logical and intelligent debate because the morons have bought the lies. Those folks carry white flags.
With leftists yesterday is what they say it is, and tomorrow will be wonderful.
But today they will do their damned best to make everybody suffer, equally of course, for the children of course, except the ones they demand Planned Parenthood slaughter.
Yes, the glorious left, where would we be without them.
Things that make you say hmmmmmm
I heard it on the radio, Israeli forces said they detected weapons being moved out. They are no dummies, I believe they were right too!
Mass destruction? Life yes, property no. Sooner it would be weapons of mass killing.
And there were lots of that stuff found there. They simply dumped it or took it out of country.
I asked my neighbor down the road, since he was one of those deniers, of how easy he thought it would be to hide one quart of liquid/something in a city.
You might actually already know all that, but what's the use of being a liberal if you can't lie, cheat, and steal, eh?
"Of course, US troops never managed to find any such weapons after the invasion."
Keep repeating a lie enough times and idiots will believe it. They did find some but it was dismissed ads "pre-gulf war WMD" or "not militarily ready WMD"
From liberal factcheck.org:
"and discovered only a few random chemical weapons."
So which is it? "never found any" or "only found a few"?
David Corn's rag ripping a woman who could whip every testosterone challenge dope smoking male on their staff....
That's cool. Just get ready to pronounce it correctly, punks: "Senator Joni Ernst".
The Iraq War Resolution, which gave George Bush the authority for military force against Iraq had 23 paragraphs. Only 4 mentioned WMD, and that is all anyone talks about.
The other 19 were more than sufficient given that Iraq had signed and agreed to the terms of an armistice in 1991.
Another guy named Adolph Hitler was not held to the terms of an armistice (even when he was relatively weak when he violated those terms) signed by his nation and we can see where THAT got us.
550 Metric Tons of yellowcake uranium removed from Iraq
What are the chances that they'd refuse to investigate, and even outright lie to make George Bush look bad?
Well, the leftists in the Democrat party won't believe Israel...you remember how the loudly booed the Jews at their convention?
That FACT was omitted from most newscasts, as it casts a true and shining light on the Democrat party: anti-Semites and God haters.
There WERE WMDs in Iraq!
Well leftists are good at ignoring the facts..they won't say where Assad's weapons came from because then they would have to admit that Saddam DID have weapons of mass destruction, would destroy their whole narrative
I worked with eapons and even the fact that they really didn't find a massive cache of weapons there is a difference in comparing weapons. Chemical weapons are not built like regular bombs and such their size is not in giant dumb bombs and missles but just that a little chemicals can go a long way. Remeber when Chohen and the 5 lb. bag of sugar he used when he was Clinton's Sec. of state.
Why were advanced Mig aircraft found buried in the sand in Iraq? What else might have been buried or secreted somewhere?
Syria was known to have it's own chemical weapons program for decades before we invaded Iraq. I'm not saying they didn't also get some from Saddam, just that they already had them.
I agree. And you know who ELSE agreed?
Bill Clinton
Hillary Clinton
John F. Kerry
And the multitudes of democrats who voted for the Iraq war.
You know, the ones who looked at the intelligence available to them.
"Saddam had WMDs on the day I left office."-Bill Clinton.
When the Left has to disparage the words of a leftist like Bill Clinton, you KNOW they are on thin ice.
Not only that, it was Democrat Senator Jay Rockefeller who was the first to call Iraq "an imminent threat".
It is a classic case of the LIEberals telling a lie over and over again until it become accepted "Truth".
The Bush Administration had, but did not release, information proving that Saddam had WMDs. I have no idea why.
they were shipped off to Syria, Libya and Russia while the U.N. and the U.S. Congress dickered over a resolutions supporting military action if Saddam did not officially account for them and turn them over
Saddam fully expected, with the help of the American Left, to make Iraq another "Vietnam", return to power and get his WMD materials back from his friends.
I suspect some of what the U.S. got from Gaddafi began its WMD life in Iraq as is the case with Syria as well, and some I suspect Russia still has.
If President Bush KNEW there were no WMD's in Iraq, we would have found them the first day of the War.
My standard line to a Liberal who blurts out the old Bush Lied, People Died meme.
Not to mention the military assets they had hidden like fighter jets.
Not to mention the munitions they used to make roadside bombs to kill Our people for years.
There were 30,000 Kurds who might have had an opinion supporting hers.
These no wmd folks are bat squeeze crazy.
Only a lemming would honestly believe Saddam either didn't have wmds or was really trying to get everyone to believe he had them via violating all the UN resolutions against him.
What is to be gained by their continual denial that there was chemical and biological weapons in Iraq and they were trying to get nuclear weapons?
I guess they can neuter future attempts to control those weapons.
Hypocrisy by the left is the new normal for them.
At 76 years of age, I've been watching 'rats for a long, long time - trust me, it's their old normal.....
DAMN! When did FR Moderators start allowing Articles from that Liberal, Left-wing "MOTHER JONES" yellow journalism rag? Holy Shit Batman!!!
I watched the video. Joni handled it perfectly. Anyone who has half a brain knows that Saddam Hussein DID have weapons of mass destruction. Good thing nobody has a paid subscription to "MOTHER JONES" except fags, lesbians, child molesters and Registered Sex Offenders.
Chemical Ali had already used chemical weapons for mass killings of opposing factions in Iraq.
So it is never a question of if, it is is only a question of what happened to them.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.


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Nothing But You: Love Stories From The New Yorker Paperback – May 5 1998
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For decades The New Yorker has kept the short story in America's literary consciousness. While the sales of novels have eclipsed those of short stories in the marketplace, short-story writers take comfort in the fact that each week their craft is showcased in the pages of one of the country's best-known publications. Now Roger Angell, a senior editor at The New Yorker, has assembled a collection of stories by the likes of John Updike, Alice Munro, Woody Allen, and Raymond Carver. Culled from more than 30 years of issues, these stories are united by the theme of love, a term that covers a multitude of emotions: romantic love, platonic love, parental love, filial love, and love for mankind, not to mention lost love, twisted love, nostalgic love.... These 38 stories cover them all. --This text refers to an out of print or unavailable edition of this title.
From Publishers Weekly
Modern love in all its unpredictable reality unfolds in this delightfully unorthodox anthology of 38 New Yorker stories from the past three decades. Many of the selections are love stories only in the broadest sense, viewing love as an element inextricably woven into the fabric of characters' lives. For example, William Maxwell's "The Man in the Moon" explores the emotional effect over three generations of a once-prominent Midwestern family's scandals, self-deceptions and failures on the male narrator, now an elderly historian. In Daniel Menaker's "Influenza," a self-described "neurotic school-teaching Jew" at a posh private school in Manhattan spars with his hectoring Cuban Freudian analyst as he carries on a torrid affair with a wealthy, sex-starved, WASPish widow. Angell, a longtime senior editor at the New Yorker, adventurously brings together stories that delve into the diversity of love: a macho New Orleans 16-year-old's sexual confusion over a furtive homerotic kiss (Ben Neihart's "Hey, Joe"); an English adventurer's quasi-clinical investigation of eros as part of a 1920s surrealist circle in Paris (Julian Barnes's "Experiment"); a devoted May-December couple-she 35, he 78-bravely facing her terminal illness (Mary Robison's "Yours"). Some may feel the humorous entries (by Woody Allen, Ian Frazier and others) fall flat, and others may find the entire roundup of wry, fiercely observant stories too cerebral or unromantic. Yet there are strong selections from Ann Beattie, John Cheever, Raymond Carver, Edna O'Brien, V.S. Pritchett, Jean Rhys, John Updike and lesser-known writers. Timed to coincide with Valentine's Day, this quirky omnibus makes a funny Valentine indeed. Illustrated. Local Valentine's Day readings by contributors.
Copyright 1996 Reed Business Information, Inc. --This text refers to an out of print or unavailable edition of this title.
Customer Reviews
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Earlier in 2002, I had read Victorian Love Stories: An Oxford Anthology edited by Kate Flint, a wonderful, imaginative anthology that covers the gamut of love, from earnest and longing to the impulsive and painful, from gritty realism to the fantastic and the supernatural. I had had Nothing But You for a while, and it seemed natural to read it as a follow-up to the Victorian anthology. This proved to be a mistake; the contrast between the two highlights the shallowness of the New Yorker stories.
There are a few gems, such as "Marito in Città" by John Cheever, "The Diver" by V. S. Pritchett, "Eyes of a Blue Dog" with Gabriel Garcia Marquez's magic surrealism, "The Kugelmass Episode" with Woody Allen's characteristic offbeat humour and angst, and "Here Come the Maples" with a touch of irony by John Updike. One story by a lesser-known writer, "In the Gloaming" by Alice Elliott Dark, stands out for beautifully conveying the tragedy of loss and alienation, not through death, but through the chains and barriers that life erects to prevent insight and truer love between the mother and son and between them and the distant, unloving father. Impending death finally begins to break down those barriers and reveal the humanity of mother and son to one another.
For the most part, however, these highlights are overwhelmed by the blandness of the rest of the selections. Somehow, this collection about "love" seems to miss many of love's elements-affection, depth of feeling, passion (depth of emotion of any kind), perception, dedication.Read more ›
My three favorite stories were Gabriel Garcia Marquez's classic "Eyes of a Blue Dog," John Cheever's previously anthologized "Marito in Citta," and Alice Munro's recent "The Jack Randa Hotel." Each of these stories, like most of the best stories in this book, works so well because it conveys the intensity and idealism and adventure of love but is also grounded in the concrete, mundane details of everyday life. Other standouts include Alice Elliott Dark's recent but already classic "In the Gloaming," Katherine Keiny's charming, Jane Austenish "How to Give the Wrong Impression," R. Prawer Jhabvala's culture-clashing "The Man with the Dog," Bobbie Ann Mason's hilarious and moving "Love Life," John O'Hara's piercing "How Old, How Young," Raymond Carver's Edgar Allan Poe-imitating "Blackbird Pie," and Mary Grimm's probing "We."
As the editor, Roger Angell, and other reviewers here have noted, the book is not all full of happy endings and is not even always about passionate love affairs per se, but the broad theme of love is the perfect motif to carry along a short fiction anthology, and this theme keeps you moving through the stories just as love in real life keeps you moving through the everyday ups and downs of being with a romantic partner. One of the best short story anthologies I've read in a while.
So, basically, it did make me feel like crap; but what a read.
Most recent customer reviews
These stories are nearly all wonderful, some are brilliant, and most are unavailable in other anthologies. Read morePublished on June 25 2004 by Carol Peters
The New Yorker publishes great writers, and great writers are worth reading. This collection, by focusing on a single theme, shows us familiar names often writing on an unfamiliar... Read morePublished on July 11 2000 by Jussi Bjorling
When I think of love stories, I tend to think of something that touches the soul. While these stories were good and well compiled, they didn't touch me in any way--with the... Read morePublished on July 25 1999
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There are two schools of thought about how a stock will behave relative to the market, and like any investment strategy or philosophy, both have their advocates and adversaries.
- Technical analysis, which involves detecting patterns in security prices, goes on the assumption that the price of a stock - like the price of everything else - is a matter of supply and demand. Technical analysts, or technicians, generate and interpret charts of the price and volume histories of stocks to predict movement in stock prices according to perceived trends.
- Fundamental analysis, which examines the earning potential of the company issuing a stock, goes on the assumption that a share of ownership of a company has an intrinsic value that is a function of the underlying value of the company as a whole. Fundamental analysts report which shares are undervalued by the investor community and which are overvalued, then trust the market to make corrections.
In the world of stock analysis, fundamental and technical analysis are on completely opposite sides of the spectrum. Earnings, expenses, assets and liabilities are all important characteristics to fundamental analysts, whereas technical analysts could not care less about these numbers. Which strategy works best is always debated, and many volumes of textbooks have been written on both of these methods. We'll discuss each in turn.
Technical Analysis
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I am using NumPy to do some calculation on finding the Y intercept, through an Aperture between a big box and a small box. I have over 100.000 particles in the big box, and around 1000 in the small one. And it's taking a lot of time to do so. All the self.YD, self.XD are very large arrays that i'm multiplying.
PS: The ind are indexes of the values that need to be multiplied. I had a nonzero condition before that line in my code.
Any ideas how I would do this calculation in a simpler way?
YD_zero = self.oldYD[ind] - ((self.oldYD[ind]-self.YD[ind]) * self.oldXD[ind])/(self.oldXD[ind]-self.XD[ind])
Would using multiply, divide, subtract and all that stuff of Numpy. make it faster? Or if maybe if i split the calculation. for example.
to do this first:
YD_zero = self.oldYD[ind] - ((self.oldYD[ind]-self.YD[ind])*self.oldXD[ind])
and then the next line would be:
YD_zero /= (self.oldXD[ind]-self.XD[ind])
Any suggestions?!
I have been trying to figure this out, in a while now, but not much progress. My concern is that the denominator :
self.oldXL[ind]-self.XL[ind] == 0
and I am getting some weird results.
The other thing is the nonzero function. I have been testing it for a while now. Could anybody tell me that it is almost the same as find in Matlab


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text: Insa Riepen Local News Hour - Tuesday, Feb. 16, 2016 By Leslie Thatcher • Feb 16, 2016 On today's program, Leslie Thatcher speaks to Summit County Manager Tom Fisher; Summit Community Power Works Project Manager Mary Christa Smith has information about a bulk-buy purchase of smart thermostats; Recycle Utah director Insa Riepen has her monthly update and Chris Haslock with Team Park City United has the latest results from the Youth Olympic Games in Norway. Local News Hour - Tuesday, January 19, 2016 By Leslie Thatcher • Jan 19, 2016 KPCW Summit County Manager Tom Fisher comes in to preview the agenda for Wednesday's County Council meeting. Recycle Utah Executive Director Insa Riepen provides a monthly update of the county's sustainability issues. As a special feature, Filmmaker Jamie Redford comes in to promote the Park City High School screening of Paper Tigers, a documentary of a group of teenagers who attend an alternative high school in Walla Walla, Washington. Yuletide Trash Tips from Recycle Utah By Renai Bodley • Dec 15, 2015 Recycle Utah The days of brown paper packages tied up with string are long past. Now Christmas presents are blinged out like never before. And when you're finished with all the finery, don't dump it together in the recycle bin. KPCW's Renai Bodley tells us why: Here's a link to the Recycle Utah website. Local News Hour - Tuesday, December 15, 2015 By Leslie Thatcher • Dec 15, 2015 On today's program, Leslie Thatcher speaks with Summit County manager Tom Fisher, Bill Rock COO of Park City Mountain Resort and Mark O'Connor CEO of skipatrol.net talk about the close vote authorizing the Park City Ski Patrol to unionize. Recycle Utah director Insa Riepen has her monthly update and Automotive Journalists Paul Schmucker and Todd Deeken talk about the new film Pilgrimage, which has a free screening Wednesday 6:30 pm at Jim Santy Auditorium. Local News Hour - Tuesday, November 17, 2015 By Leslie Thatcher • Nov 17, 2015 On today's program Summit County Budget Manager Matt Leavitt previews the 2016 county agenda. Park City Resort COO Bill Rock talks about opening day on Saturday for the county's largest ski resort. Sherrie Wellman has details about getting inspections and business licenses for nightly rentals. Recycle Utah Director Insa Riepen has her monthly update and Richard Bullough and SaRene Brooks with Summit County Health Department have details on a diabetes prevention and education initiative. Local News Hour - Tuesday, October 10, 2015 By Leslie Thatcher • Oct 22, 2015 On today's program, Summit County Manager Tom Fisher reviews the agenda for Wednesday's County Council meting. Park City Council Candidate Hope Melville talks about her candidacy. Recycle Utah Director Insa Riepen has her monthly update and Park City librarians have details on the current art exhibit and stuffed animal slumber party. This Green Earth - October 6, 2015 By Chris Cherniak & Katy Wang • Oct 6, 2015 KPCW On today's show Chris Cherniak and guest host Katy Wang covered three types of harvesting activities. First, beekeeper Doug Fryer discussed how he harvests honey from his local hives. What's the process like? And what do all those female bees do for the next five months? Then Ken Kullack, executive director of the Summit Community Garden, discusses how their "garden grew." He also talked about their garlic planting event they will be holding at the garden Saturday, October 10. Local News Hour - Tuesday, September 15, 2015 By Leslie Thatcher • Sep 15, 2015 Egyptian Theatre Company On today's Local News Hour, host Leslie Thatcher speaks with Wasatch County Manager Mike Davis about the JSSD and Mayflower. Summit County Manager Tom Fisher reviews Wednesday's county council meeting, Recycle Utah Director Insa Riepen provides her monthly update and Randy Barton talks about his one-man, two-act performance, Famous and Infamous, this weekend at the Egyptian Theater. This Green Earth - July 7, 2015 By Chris Cherniak & Nell Larson • Jul 7, 2015 recycleutah.org On this episode, hosts Nell Larson and Chris Cherniak spoke with Insa Repien, Executive Director at Recycle Utah. Insa reflects on Recycle Utah's twenty five years of providing recycling and re-purposing services to the community and what challenges lie ahead. Next up, a conversation with Paul Spitler of the Wilderness Society about the deadline looming for the Land and Water Conservation Fund, and what will happen if the fund is not reauthorized by Congress. During Sundance, Bring Glass To Local Recycle Center By Lynn Ware Peek • Jan 20, 2015 Got Glass? Take it to the recycle center that's located off of Bonanza Drive and Kearns Boulevard on Woodbine Way. It's one of the only places in town that will recycle it. Lynn Ware Peak has more. Pages1 2 next › last »


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Tattoo Submission: Phoebe T (Vancouver) - 27th July 2012
Let it be. And just stay strong :).
Let it be. And just stay strong :).
Elena (UK)
Ivessita (Santo Domingo)
Christin (Cuxhaven, Germany)
I've been searching a long time for the perfect picture to cover my back.
Finally I found it.
John Keats saying "what the imagination seizes as beauty must be truth"
I thought I'd do this post even though it isn't tattoo related because quite simply I love blogs. I love blogging and I like reading blogs, I follow hundreds. I follow all of the big ones that every...


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By Allison Epstein Ah, the selfie. The autobiography of the photographic world. The 2013 Word of the Year for the Oxford English Dictionary (or OED). And the subject of many a heated debate. It's difficult to escape its influence, either in your Facebook news feed or in the mainstream media. The OED estimates that the usage … [Read more...]
Pink Profits: How Corporate Cancer Advocacy Preys on America
By Ashley-Michelle Papon First, it was the location of your purse. Then, it was the color of your bra. Most recently, if you spent any amount of time on Facebook this past October, you probably had a few friends reminding women to go braless for breast cancer awareness. As October is Breast Cancer Awareness Month, this latest … [Read more...]
Liberate Halloween Action Kit!
By the White Noise Collective They're ba-ack! (shudder) With Halloween quickly approaching, and costume shops like Spirit Halloween opening their doors, many of us are cringing at the thought of another Halloween full of racism, sexism, heterosexism and the full range of offensive apparel we annually witness. In response, we … [Read more...]
Disney Starlets Getting Thinner?
By Gabby Vachon For the last decade, The Disney Channel has successfully launched the careers of the most popular teen superstars. But are these young Hollywood starlets getting thinner, and what message does that send young viewers? I was perusing Tumblr when I found this picture of the three "generations" of Disney … [Read more...]
"Yoga Body": The Conspiracy
By Danielle Prohom Olson, Yoga Divine Yoga I thought I'd said all I wanted on body image and yoga in my last post but controversy in the yoga world regarding a certain video has left me feeling I didn't say nearly enough. Or say it clearly enough. So let me try again. The taut and toned 'yoga body' on display in the media … [Read more...]
When We Were Free To Be: Revisiting A Classic
By Amy Jussel, Shaping Youth Last year marked not only the 40th Anniversary of Title IX changing women's sports forever, it was also the 40th Anniversary of the cycle-breaking, movement-making pop culture childrens' classic Free to Be, You and Me created by one of my very first childhood 'sheroes' Marlo Thomas. Marlo Thomas' … [Read more...]
Lyrical Lacerations, from NWA to Rick Ross
By Anne Desrosiers Rappers make songs under the creative licenses of their whims, songs are released, and sometimes these songs top the charts. Other times they become catch phrases that become part of urban lexicon, and other times they create a firestorm of criticism and backlash. Certainly ever since music has been made … [Read more...]
Bridget Jones Made Me Do It! Does Chick Lit Negatively Influence Women's Body Image?
By Sayantani DasGupta I read a fascinating piece in The Guardian UK recently, with an even more fascinating headline: "Chick lit 'harms body image', study finds." At first glance, this seems highly plausible. Just the name 'chick lit' implies something at least intellectually (if not psychologically) unsavory. We are women, not … [Read more...]
Stop Fanning the "Mommy Wars": Enough with the "Breastfeeding Bullies" Articles, Jezebel!
By Sayantani DasGupta I could hardly believe it when I saw the headlines: "The pressure to breastfeed is getting out of hand"! and "Sorry – You can't guilt trip me about bottle feeding my kids"! It's not that I'm surprised by anti-breastfeeding attitudes in the U.S. After all, this is a country where, women are still … [Read more...]
"You Look So Different on Facebook…"
By Sheena Vasani, Intern (2011) Editors note: This blog post was originally posted Nov 1, 2011. We are sharing it again for our visitors to consider how airbrushed photos (whether your own, or those in magazines) impact your well-being and sense of self. What makes your physical beauty exceptional? Ironed out pimples, wrinkles, … [Read more...]


text: 12 Lake at Dawn by Kevin Mowatt Best Sellers Trending Art Best Selling Paintings Best Selling Abstract Art Prints Best Selling Photography Best Selling Posters Popular Subjects Animals Architecture Childrens Art Floral & Still Life Landscape Maps Military & War Music Science Fiction & Fantasy Skylines Spiritual Transportation Featured Artists Brickhut Cozamia Eric Joyner Erin Ashley James Niehues Jennifer Lommers Jonas Gerard Marcia Baldwin Mark Lawrence Michael Creese Michael Tompsett Collections ArtLoversOnline Design Pics The Fine Art Masters Panoramic Images Retro Images Archive StockTrek Images WorldWide Archive Create Your Own Photo Canvas Custom Frame Photos Lake at Dawn by Kevin Mowatt Sign inCustomer Service Cart Houzz Share on Tumblr Tweet +Add to Cart Available Sizes inches / cm Petite $57.5 Small $69 Medium $86.25 Large $115 Grande $230 » component prices Print Frame Mats Glazing Fitting Customize Framing or choose Canvas Print Customize Canvas or choose Framed Art Print Click to save as artist's preferred kit Paper Enhanced MattePremium Photo GlossyPremium Photo LusterUltraSmooth Fine ArtHahnemuhle Photo Rag 308Hahnemuhle Fine Art PearlHahnemuhle Torchon Mounted? ★★★☆☆ Details Paper print only, too large to frame online. Frames Choose a color » ø Top Mat | Middle Mat | Bottom Mat ø Glazing Style Soft EdgeWhite EdgeBlack EdgeImage WrapUnstretched 1½ inches thick (3.75 cm) Product Details Artist grade canvas, archival inks, wooden stretcher bars, and UVB protective coating Availablity Usually ships within five business days. Artist Kevin MowattCollection Artwork Popular Configurations Stretched Canvas Modern Lines Contemporary White Classical Baroque Unframed print Explore More from the same collection View All Kevin Mowatt's Recent Work About the artist Kevin Mowatt, Easton, MA Member Since May 2007 Artist Statement I recently graduated from Roger Williams University in Rhode Island with my Masters Degree in Architecture. I am looking for a job in the Boston area at an architecture firm. While searching for work, I am open to all opportunities for architectural or graphic design, from house design ideas to corporate logos. Please view my website above for more information about the work I have produced in school, including my graduate thesis project entitled "Adaptive Housing: Transformation and Growth in the Urban Environment," which can be viewed and is available for sale on Blurb at http://www.blurb.com/bookstore/detail/1161262 Community Comments Catalog Details Product No 2223626 Subjects Landscape, Mountains, Nature & Outdoors Style Medium Tags Kevin, Mowatt, dawn, dusk, evergreen, fog, lake, mist, pine, sky, sunset, water Create Frame Photos Photos on Canvas Sell Sell Art Online Become an Affiliate Get a Trade Account Common Questions Company Info About Us Contact Customer Comments Return Policy Social Tumblr Pinterest Twitter Facebook Instagram Our Wall Art Family CanvasOnDemand | Photo Canvases GreatBigCanvas | Decorate Huge Terms of Service Privacy Policy Copyright © 2016


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Bella Swan is suffering from another bout of her continual insomnia when she comes across a velvety voice on the radio late at night. AU, All-Human.
Alice couldn't see much of Bella's future now. I had watched her try a few times this evening and she had been disturbed, even frightened by some of what she'd seen. But not frightened enough that she wouldn't leave like Edward demanded. No, we were all going to leave. Some of us would just be kicking and screaming all the way to the airport. It was the only rebellion I would be allowed, for now.
An excerpt from Rebellion, the sequel to Dreamwalker
(Written before BD) Unchangeable has unexpected complications. J/B/E
Bella doesn't believe in love. Edward relies on it to woo women into bed. Where will they end up one year and one bet later? Will they be able to change each other? Is change possible? Or are some things better left unchanged?
Bella and Edward have been friends since they were children. They really like each other, and to be honest, its obvious to everyone! Well, except to them. They are destined to be together but why does everything go wrong?
This story is updated more frequently at ff.net
Ditched by her friends, and desperately seeking out a bathroom, Bella stumbles onto something she shouldn't have.
When Bella meets Edward, she realizes there's more than a thin line between love and lust. There's so much she never knew about desire, but even more that she never about herself.
Don't be mislead by the prologue - there's nothing bland about the plot!
Disclaimer: Stephenie Meyer owns all things twilight!
What if Edward didn't get to Bella before Tyler's van hit her...what if he responded to her blood...? What if he bit her? Where would they be, how would their lives change...a view into an alternate Twilight.
What would happen if Leah imprinted?
What would happen if it was on someone we knew?
Ahh, unrequited love.
Or is it?
I never gave a thought about what marriage really meant, i loved Jake and i was happy. isn't that enough? i guess we will have to see.
This is an adaptation of New Moon and it takes place a year after Edward left Bella. Bella was heartbroken and devastated, on the verge of a catatonic depression but anger and resentment helped her heal as well as, Jacob, who she has become very close with. My story picks up a year after the breakup at Ben and Angela's wedding. (Yes, they married early). Please keep in mind that this is my first attempt at writing and that it is very amateur. Additionally, please be advised that this adaptation is very graphic and contains strong sexual passages. Any feedback, good or bad, would be greatly appreciated. Hope you enjoy.
Bella and Alice are finally in High School. Alice was more than excited to meet new boys and have fun. Bella remains unamused until she meets the dashing senior named Edward Cullen.
After two years, Lily finally knocks on Edward & Bella's door...
Part two of "Lily Honeycutt"
A oneshot sequel to First Kiss - don't worry, you don't have to read First Kiss to understand this. Written for Ysar for the April '09 Support Stacie Auction.
Bella has been with Jacob for four years and everyone thinks they have the perfect relationship. Their friends and family expect an engagement any day, but Bella is having second thoughts. A story about old love, new love, and friendship.
Canon pairings. Slightly OOC. Rated for later chapters.
2009 Nominee, Best AU AH, Most Romantic Moment, Indie TwiFic Awards
2009 Nominee, Character You Wish Was Real (Jasper), The Faithful Shipper Awards
A small-town music store... Several music-obsessed slackers with a penchant for sexual misadventures, disastrous love lives and a little too much alcohol... Customers with horrible taste in CDs... Thousands in missing cash deposits... and Carlisle's not even supposed to be here today!
Disc Jockeys is the story of Velvet Records, one of the few remaining independent music stores in Washington State. From shoplifters to has-been singers, from franchise threats to the complicated love lives of the inhabitants within, the employees of Velvet handle it all, under the watchful gaze of Carlisle, their long-suffering manager.
This AU, AH is a spoof of Empire Records blended with healthy cynicism of the Clerks vein. If you haven't seen Empire Records, have no fear; this fic assumes you haven't the faintest idea what "Damn The Man - Save The Empire!" means (but SEE IT because it's an awesome flick).
This fic is rated NC-17 for underage drinking, drug use, sexy naughty times, dark issues including sexual assault and abuse and language. Slightly OOC for some players, canon pairings apply (eventually).
This story completely ignores the vampires and focuses on the wolves. I have always wondered about Jacob's animal side and decided to experiment with a smutty one-shot.
The pack has formed and Jacob is the leader. I made up a fiancée for him to avoid any character clashes. This is a peek at what might happen if the wolf comes out to play in the bedroom.
AU and OOC in the sense that Jacob is not in love with Bella, but engaged to a La Push girl named Rebecca. Everything else could be possible, but doesn't really matter, because, let's face it, this is not really about plot.
Bella Swan is about to embark on the biggest tour of her musical career, but all that is put at risk after a night at a New Year's Party in London. And once the press finds out her secret, all hell will break lose. Follow Bella and Edward as they try to make sense of everything when it all falls apart.
It's been 100 years since Edward left Bella and she's still kicking. What will she do when she strays across her once would-be family in the same place it all started: Little Forks, Washington?
The government created a pathogen, a virus, that was used on soldiers to make them stronger. It got out of hand though and vampirism was born.
Bella and Jacob are in charge of a task force named Twilight who are sent to the island that was once Washington State. It is called Vampire Island and home to most of the vampires. It is while on the island that Bella's life is changed forever. When she meets a small family of vampires that are nothing like the rest.
Can she do what she is trained to do, kill vampires? Will this vampire family change her world entirely?
Bella is never alone. The warm caress of a pair of loving eyes has followed her throughout her entire life. Whenever she turns her head to find the source of the intense stare she is left staring into nothingness.
Soon she will be confronted by the eyes that have followed her.
And at that very moment, everything that Bella knows about herself and everything that Bella knows about the world around her will completely unravel.
Soon the veil will be lifted.
Bella is thrust into a 2,000 year old war and she must rise above the danger or she risks losing all that she holds closest to her heart.
Eight long years have passed and while it's been merely a drop in the bucket for a family of immortals, for Jacob it's been watching the love of his life grow. Now she's coming of age and he's as ready as she is-- but her parents have other ideas.
Clumsy Bella breaks something. Helpful Jake tries to fix it. New Moon missing moment. One-shot.
Renesmee and Jacob were as happy as could be thirty four years after Nessie was born. Now she's grown up and making decisions that could affect the entire Olympic Coven.
A Russian Doll is one that is hollow, and can be taken apart time and time again until the smallest solid doll remains.
After the events of Breaking Dawn, with no true family left to her, Tanya reminisces on the events of the past, from her failed love, Edward Cullen, to her mother's death and the immortal children, and also what transpired during Twilight, New Moon, Eclipse and Breaking Dawn.
This is Tanya's story.
All publicly recognizable characters, settings, etc. are the intellectual property of their respective owners. The original characters and plot are the property of Stephenie Meyer. No copyright infringement is intended.