SRB water impact velocity trade study

The results of the attrition/cost studies which formulated the data base for the recommendation to reduce the Space Shuttle Solid Rocket Booster's nominal vertical water impact velocity to 85 feet per second is presented

Reduced tubulin tyrosination as an early marker of mercury toxicity in differentiating N2a cells

The aims of this work were to compare the effects of methyl mercury chloride and Thimerosal on neurite/process outgrowth and microtubule proteins in differentiating mouse N2a neuroblastoma and rat C6 glioma cells. Exposure for 4 h to sublethal concentrations of both compounds inhibited neurite outgrowth to a similar extent in both cells lines compared to controls. In the case of N2a cells, this inhibitory effect by both compounds was associated with a fall in the reactivity of western blots of cell extracts with monoclonal antibody T1A2, which recognises C-terminally tyrosinated α-tubulin. By contrast, reactivity with monoclonal antibody B512 (which recognises total α-tubulin) was unaffected at the same time point. These findings suggest that decreased tubulin tyrosination represents a neuron-specific early marker of mercury toxicity associated with impaired neurite outgrowth

The pleasures and perils of inheritance

Facing death, reflecting on one’s legacies (material and ethical, personal and political) and the legal and interpersonal attempts to resolve or prevent inheritance conflicts, all bring to the fore constructions of memory and identity, intergenerational relations, and the complexities of doing and undoing family and kinship. Consequently, drawing attention to inheritance, keeping sight of it, and bringing it into play is a useful piece of the puzzle of ageing across a range of disciplines and this article provides an overview of some of the key themes in this emerging field

The heritability of telomere length among the elderly and oldest-old

A tight link exists between telomere length and both population doublings of a cell culture and age of a given organism. The more population doublings of the cell culture or the higher the age of the organism, the shorter the telomeres. The proposed model for telomere shortening, called the end replication problem, explains why the telomere erodes at each cellular turnover. Telomere length is regulated by a number of associated proteins through a number of different signaling pathways. The determinants of telomere length were studied using whole blood samples from 287 twin pairs aged 73 to 95 years. Structural equation models revealed that a model including additive genetic effects and non-shared environment was the best fitting model and that telomere length was moderately heritable, with an estimate that was sensitive to the telomere length standardization procedure. Sex-specific analyses showed lower heritability in males, although not statistically significant, which is in line with our earlier finding of a sex difference in telomere dynamics among the elderly and oldest-old

Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients

The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors

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