OF RUPTURES AND RAPTURES: LOCATING IDEOLOGY WITH LIDAR IMAGERY

Archaeological praxis necessarily requires at least one object (a piece of technology or something that functions as an object) to articulate and explain ideologies from the past. This is problematic because ideology is abstract and difficult to locate in the archaeological record in reified form. Archaeology’s preoccupation for over 100 years has been the systematic location, identification, and excavation of discrete artifacts; features, and sites; interpreting meanings from comparative studies and data sets; and putting the past in order all while documenting change over time. Historical archaeologist Mark P. Leone identified fences, the Plat of the ideal City of Zion, Mormon temple architecture, plan, and program, and dams on the Little Colorado River in Arizona as the technologies and objects that facilitated Mormon settlement, survival, and adaptation in the Intermontane West of North America in the 19th and early 20th centuries. In 2010, Leone revisited his life-work including a critical re-examination of his original research on Mormon fences, the Plat of the ideal City of Zion, and Mormon temples. In the interim, Leone read Philosopher Slavoj Žižek’s The Sublime Object of Ideology. Žižek defined three types of ideological objects: voids (or absences); large, unattractive objects left over or resultant from the past of which we are all aware; and an index or circulating object, one that is known to exist or have existed and requires an ideological structure to understand it, e.g. Mormonism. Žižek’s definitions and rubric have a potential to answer a research question that emerges out of Leone’s life-work: What was or is the object of Mormon ideological desire in the archaeological record (OMIDAR)? The ultimate ideological desire of 19th and early 20th century Mormonism was the creation of a New Zion. A test revealed that none of the four technologies Leone previously identified completely meets Žižek’s criteria. This dissertation undertook a critical examination of LiDAR imagery of the Mormon Row Historic District (MRHD) (48TE1444) in Grand Teton National Park (GTNP) in which a provisional Mormon irrigation pattern (MIP) was identified. Leone considered irrigation associated with dams as an important factor, but did not consider it as an ideal technological object perhaps because, unlike fences, settlements, temples, and dams, irrigation was not seen as a unary object. The MIP was searched for along the Little Colorado River in Arizona. In each of the settlements in Leone’s original study area at least one relict field containing the MIP was located. As a technology and unary object, the MIP was tested against Žižek’s criteria and it passes. It is averred that the MIP is the metaphysical and material ‘footprint’ of New Zion—an ideological void. The authorizing heritage discourse (AHD) concerning irrigation features is also challenged and a recommended revision concerning their significance and eligibility for listing on the National Register of Historic Places is offered

Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival