Everyday Diplomacy: UKUSA Intelligence Cooperation and Geopolitical Assemblages

This article offers an alternative to civilizational thinking in geopolitics and international relations predicated on assemblage theory. Building on literature in political geography and elsewhere about everyday practices that produce state effects, this article theorizes the existence of transnational geopolitical assemblages that incorporate foreign policy apparatuses of multiple states. Everyday material and discursive circulations make up these assemblages, serving as conduits of affect that produce an emergent agency. To demonstrate this claim, I outline a genealogy of the UKUSA alliance, an assemblage of intelligence communities in the United States, United Kingdom, Canada, Australia, and New Zealand. I then trace the circulation of materialities and affects—at the scales of individual subjects, technological systems of mediation, and transnational processes of foreign policy formation. In doing so, I offer a bottom-up process of assemblage that produces the emergent phenomena that proponents of civilizational thinking mistakenly attribute to macroscaled factors, such as culture

Cone-beam CT reconstruction with gravity-induced motion.

Fixed-gantry cone-beam computed tomography (CBCT), where the imaging hardware is fixed while the subject is continuously rotated 360° in the horizontal position, has implications for building compact and affordable fixed-gantry linear accelerators (linacs). Fixed-gantry imaging with a rotating subject presents a challenging image reconstruction problem where the gravity-induced motion is coupled to the subject's rotation angle. This study is the first to investigate the feasibility of fixed-gantry CBCT using imaging data of three live rabbits in an ethics-approved study. A novel data-driven motion correction method that combines partial-view reconstruction and motion compensation was developed to overcome this challenge. Fixed-gantry CBCT scans of three live rabbits were acquired on a standard radiotherapy system with the imaging beam fixed and the rabbits continuously rotated using an in-house programmable rotation cradle. The reconstructed images of the thoracic region were validated against conventional CBCT scans acquired at different cradle rotation angles. Results showed that gravity-induced motion caused severe motion blur in all of the cases if unaccounted for. The proposed motion correction method yielded clinically usable image quality with  <1 mm gravity-induced motion blur for rabbits that were securely immobilized on the rotation cradle. Shapes of the anatomic structures were correctly reconstructed with  <0.5 mm accuracy. Translational motion accounted for the majority of gravity-induced motion. The motion-corrected reconstruction represented the time-averaged location of the thoracic region over a 360° rotation. The feasibility of fixed-gantry CBCT has been demonstrated. Future work involves the validation of imaging accuracy for human subjects, which will be useful for emerging compact fixed-gantry radiotherapy systems

fMRI scanner noise interaction with affective neural processes

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes

Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and re‐emerging phenotype is associated with graft function

Islet transplantation is an effective therapy for life‐threatening hypoglycemia, but graft function gradually declines over time in many recipients. We characterized islet‐specific T cells in recipients within an islet transplant program favoring alemtuzumab (ATZ) lymphodepleting induction and examined associations with graft function. Fifty‐eight recipients were studied: 23 pretransplant and 40 posttransplant (including 5 with pretransplant phenotyping). The proportion with islet‐specific T cell responses was not significantly different over time (pre‐Tx: 59%; 1–6 m posttransplant: 38%; 7–12 m: 44%; 13–24 m: 47%; and >24 m: 45%). However, phenotype shifted significantly, with IFN‐γ–dominated response in the pretransplant group replaced by IL‐10–dominated response in the 1–6 m posttransplant group, reverting to predominantly IFN‐γ–oriented response in the >24 m group. Clustering analysis of posttransplant responses revealed two main agglomerations, characterized by IFN‐γ and IL‐10 phenotypes, respectively. IL‐10–oriented posttransplant response was associated with relatively low graft function. Recipients within the IL‐10+ cluster had a significant decline in C‐peptide levels in the period preceding the IL‐10 response, but stable graft function following the response. In contrast, an IFN‐γ response was associated with subsequently decreased C‐peptide. Islet transplantation favoring ATZ induction is associated with an initial altered islet‐specific T cell phenotype but reversion toward pretransplant profiles over time. Posttransplant autoreactive T cell phenotype may be a predictor of subsequent graft function

Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

Extra-Activism: Counter-Mapping and Data Justice

Neither big data, nor data justice are particularly new. Data collection, in the form of land surveys and mapping, was key to successive projects of European imperialist and then capitalist extraction of natural resources. Geo-spatial instruments have been used since the fifteenth century to highlight potential sites of mineral, oil, and gas extraction, and inscribe European economic, cultural and political control across indigenous territories. Although indigenous groups consistently challenged maintained their territorial sovereignty, and resisted corporate and state surveillance practices, they were largely unable to withstand the combined onslaught of surveyors, armed personnel, missionaries and government bureaucrats. This article examines the use of counter-mapping by indigenous nations in Canada, one of the globe’s hubs of extractivism, as part of the exercise of indigenous territorial sovereignty. After a brief review of the colonial period, I then compare the use of counter-mapping during two cycles of indigenous mobilization. During the 1970s, counter-mapping projects were part of a larger repertoire of negotiations with the state over land claims, and served to re-inscribe first nation’s long-standing history of economic, social and cultural relations in their territories, and contribute to new collective imaginaries and identities. In the current cycle of contests over extractivism and indigenous sovereignty, the use, scope and geographic scale of counter-mapping has shifted; maps are used as part of larger trans-media campaigns of Indigenous sovereignty. During both cycles, counter-mapping as data justice required fusion within larger projects of redistributive, transformative and restorative justice

The POT1-TPP1 telomere complex is a telomerase processivity factor

Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 ( protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1 - TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62923/1/nature05454.pd