613 research outputs found
The marriage of reason & squalor
No full textIn his first work of fiction, artist Jake Chapman slashes the romantic novel down to bare bone and constructs his own disfigured version from the slaughtered remains.Chlamydia Love is gifted her very own tropical island by her fiancé, where she develops a grudging adoration for its real owner, the enigmatic bestselling author, Helmut Mandragorass. A battle between her fiancé and Helmut ensues, for ownership of the island and ultimately for the love of Chlamydia.This mercilessly subversive tale is illustrated by Chlamydia's watercolours entitled Visions of Morass, images inspired by the island as she struggles with her feelings of agony and ecstasy.<br/
Jake and Iris Burritt Residence
No full textPhotograph - Jake and Iris Burritt residence, Athabasca, Alberta was built in 191
Pre-Biblical and Old Testament rape law parallels: recurring androcentric themes in historic Biblical text
No full textRape legislation in ancient Near Eastern texts is very slanted in respect to a pervasive androcentric ideology that drives the punitive outcomes. Unfortunately, evidence shows the lives of women in terms of their perceived societal value are affected (often negatively) in regard to their social status; regardless of region or period. Women did not wield much social power in ancient times and the laws demonstrate resolutions for prescribed transgressions that neglected to include any consideration for the viewpoint of women; who were the primary victims of the rape offense. As a result, women suffered and were historically antagonized by the these laws which failed to protect them. This research will illuminate the disparities by examining the laws in various regions of the period and challenge the underlying themes.M.A.L.S.Includes bibliographical referencesby Jake J. Jone
Jake and Iris Burritt Residence - 02
No full textPhotograph - Jake and Iris Burritt residence, Athabasca, Alberta was built in 191
Targeting the phosphatidylinositol-3-kinase and mammalian target of rapamycin signalling pathway in MYC-driven models of B-cell neoplasia
No full text© 2011 Dr. Jake ShorttThe phosphatidylinositol-3-kinase (PI3K) / mammalian target of rapamycin (mTOR) pathway links afferent signals from the microenvironment to the cellular machinery of growth, proliferation and survival. Aberrant PI3K activity is common in cancer, providing neoplastic cells with a competitive advantage over their normal counterparts. MYC is a prototypic oncogene that is deregulated in more than half of human cancers, but its activity is not readily amenable to pharmacological inhibition. Effectors of both PI3K signalling and MYC–regulated transcriptional networks intersect at multiple levels in cellular systems. This thesis examines interactions between PI3K/mTOR signalling and MYC, specifically exploring the therapeutic potential of PI3K/mTOR inhibition in MYC-driven haematological cancer.
Eµ-Myc lymphoma is a tractable model of human Burkitt lymphoma. This thesis utilises genetic and pharmacological manipulation of the Eµ-Myc system to mechanistically define apoptosis induction by NVP-BEZ235, an ATP-competitive pan-PI3K/dual-mTOR inhibitor. By contrasting NVP-BEZ235 against more selective kinase inhibitors, we identify PI3K-related DNA damage response (DDR) kinases and mTORC-1 as key targets in this apoptotic response. NVP-BEZ235 induces p53-independent apoptosis at low nanomolar concentrations that inhibit mTORC-1 and DDR kinases, but are insufficient to further downregulate the low basal activity of PI3K and mTORC-2 in Eµ-Myc cells. Apoptosis correlates with biomarkers of stressed translational machinery and is dependent on a reciprocal induction of pro-apoptotic BMF and reductions in anti-apoptotic MCL-1. Similar activity of NVP-BEZ235 is observed in vivo, where drug treatment results in apoptotic lymphoma regressions and prolongation of survival. In vivo regressions correlate with inhibition of DDR-kinases and mTORC-1, but not antagonism of PI3K/AKT. However, genetic manipulation to activate AKT at the initiation of lymphomagenesis augments the response to NVP-BEZ235 in an ‘mTORC-1-addicted’ model of Myc-driven lymphoma. Here, NVP-BEZ235 and the allosteric mTORC-1 inhibitor, NVP-RAD001, induce curative responses.
To broaden the scope of in vivo studies we next adapt the Vk*MYC myeloma model using a syngeneic transplant approach to facilitate the testing of novel therapeutics. In this second MYC-driven system of B-cell neoplasia, NVP-BEZ235 has only modest cytostatic activity. However, the unexpected efficacy of a commonly used drug delivery vehicle, n-methyl-2-pyrrolidone (NMP), is identified in this immunocompetent model. This NMP activity is subsequently defined as immunomodulatory with striking similarities to anti-myeloma thalidomide analogues. Moreover, a complex ‘on-target’ interaction between NVP-BEZ235 and its vehicle of administration (NMP) highlights the potential for an antagonistic relationship between mTOR inhibitors and immunomodulatory thalidomide analogues in myeloma.
The divergent efficacy of NVP-BEZ235 in two closely related haematological cancer models reaffirms the importance of molecular characterisation of specific diseases when considering the clinical translation of novel kinase inhibitors. The data presented herein indicates that dual PI3K (or DDR-kinase)/mTOR inhibitor-based strategies may have efficacy in human Burkitt lymphoma, including poor risk, p53 mutated disease. Conversely, NVP-BEZ235 has a poor activity in Vk*MYC myeloma, and has the potential to attenuate immune-mediated repression of myeloma in the clinic. Careful stratification to select haematological cancers that show functional reliance on PI3K/mTOR signalling is required to effectively progress agents like NVP-BEZ235 into human patients with lymphoid neoplasia
Oregon's urban cores saw steep declines in commuter-adjusted population
No full textby Jake Procino.Converted from HTML.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
A Cold Civil War? French Historian Pap Ndiaye and American novelist Jake Lamar discuss racial turmoil in the USA and its echoes in France
No full textOn February 1, 2022, the American Library in Paris launched its Black History Month program with a conversation between two well-known figures in France’s international Black community. Pap Ndiaye is a historian of French and Senegalese descent. As a professor at Sciences Po, he popularized the study of race and identity in French academia, most notably with his book La Condition noire. In 2021, he was appointed direc- tor of the National Museum of the History of Immigration in Paris. Jake Lamar is an African American writer who has lived in Paris since 1993. He is the prize-winning author of a memoir, seven novels and a play and teaches creative writing at Sciences Po. What follows are edited excerpts of their exchange
New job ads decrease slightly over the past year, but remain elevated
No full textby Jake Procino.Covers OCLC #1420053169 and OCLC #1405921779.Converted from HTML.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
A cross-sectional analysis of the relationship between alcohol availability, neighbourhood deprivation and chronic mental health disorder in Scotland
No full textThis study explores alcohol availability in Scotland. In particular it focuses on the relationship between availability, deprivation and mental health. The study aims to a) compare three supply-measures of availability and their associations with neighbourhood level deprivation, and b) examine the association between neighbourhood availabilities of on-sales and off-sales alcohol outlets and mental health disorders. This was a cross-sectional study where alcohol availability measures were calculated for the Scottish data zone administrative geography (n = 6,976 across Scotland). Using alcohol outlet data(2016) from the Liquor Licensing Board, three measures of availability were calculated for total, on and off-license alcohol outlets: 1) kernel density estimation at 800m and 1500m search distances; 2) counts within buffers at 800m and 1500m distances; 3) distance to the nearest outlet from the population-weighted centroid of each data zone. Average outlet densities and distances were calculated for neighbourhoods grouped by their level of income deprivation and compared using one-way analysis of variance (ANOVA). Multiple linear regression models were used to estimate the association between availability of alcohol outlets and chronic-related mental health disorder. This study found that the density-based supply-measures captured the same distribution of outlets and associations with the health outcome at 800m, but not for a 1500m travel distance. This emphasises the importance of sensitivity testing in studies of this nature. Additionally, this study observed a strong positive association between exposure to off-license outlets and chronic-related mental health disorder. These findings accentuate the need for alcohol-retail legislation, particularly for those populations most vulnerable
JOLTS in Oregon
No full textby Jake Procino.Converted from HTML.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Mode of access: Internet from the Oregon Government Publications Collection.Text in English
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