Minotaurs, Not Centaurs: The Future of Manned-Unmanned Teaming

Contesting Paul Scharre’s influential vision of “centaur warfighting” and the idea that autonomous weapon systems will replace human warfighters, this article proposes that the manned-unmanned teams of the future are more likely to be minotaurs, teams of humans under the control, supervision, or command of artificial intelligence. It examines the likely composition of the future force and prompts a necessary conversation about the ethical issues raised by minotaur warfighting

Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2

AbstractThe yeast UBC9 gene encodes a protein with homology to the E2 ubiquitin-conjugating enzymes that mediate the attachment of ubiquitin to substrate proteins [1]. Depletion of Ubc9p arrests cells in G2 or early M phase and stabilizes B-type cyclins [1]. p18Ubc9, the Xenopus homolog of Ubc9p, associates specifically with p88RanGAP1 and p340RanBP2[2]. Ran-binding protein 2 (p340RanBP2) is a nuclear pore protein [3,4], and p88RanGAP1 is a modified form of RanGAP1, a GTPase-activating protein for the small GTPase Ran [2]. It has recently been shown that mammalian RanGAP1 can be conjugated with SUMO-1, a small ubiquitin-related modifier [5–7], and that SUMO-1 conjugation promotes RanGAP1's interaction with RanBP2 [2,5,6]. Here we show that p18Ubc9 acts as an E2-like enzyme for SUMO-1 conjugation, but not for ubiquitin conjugation. This suggests that the SUMO-1 conjugation pathway is biochemically similar to the ubiquitin conjugation pathway but uses a distinct set of enzymes and regulatory mechanisms. We also show that p18Ubc9 interacts specifically with the internal repeat domain of RanBP2, which is a substrate for SUMO-1 conjugation in Xenopus egg extracts

Interaction of Stress, Lead Burden, and Age on Cognition in Older Men: The VA Normative Aging Study

BACKGROUND. Low-level exposure to lead and to chronic stress may independently influence cognition. However, the modifying potential of psychosocial stress on the neurotoxicity of lead and their combined relationship to aging-associated decline have not been fully examined. OBJECTIVES. We examined the cross-sectional interaction between stress and lead exposure on Mini-Mental State Examination (MMSE) scores among 811 participants in the Normative Aging Study, a cohort of older U.S. men. METHODS. We used two self-reported measures of stress appraisal-a self-report of stress related to their most severe problem and the Perceived Stress Scale (PSS). Indices of lead exposure were blood lead and bone (tibia and patella) lead. RESULTS. Participants with higher self-reported stress had lower MMSE scores, which were adjusted for age, education, computer experience, English as a first language, smoking, and alcohol intake. In multivariable-adjusted tests for interaction, those with higher PSS scores had a 0.57-point lower (95% confidence interval, -0.90 to 0.24) MMSE score for a 2-fold increase in blood lead than did those with lower PSS scores. In addition, the combination of high PSS scores and high blood lead categories on one or both was associated with a 0.05-0.08 reduction on the MMSE for each year of age compared with those with low PSS score and blood lead level (p < 0.05). CONCLUSIONS. Psychological stress had an independent inverse association with cognition and also modified the relationship between lead exposure and cognitive performance among older men. Furthermore, high stress and lead together modified the association between age and cognition.National Institutes of Health (R01ES07821, R01HL080674, R01HL080674-02S1, R01ES013744, ES05257-06A1, P20MD000501, P42ES05947, ES03918-02); National Center for Research Resources General Clinical Research Center (M01RR02635); Leaves of Grass Foundation; United States Department of Veterans Affair

Sonic Booms in Atmospheric Turbulence (SonicBAT): The Influence of Turbulence on Shaped Sonic Booms

The objectives of the Sonic Booms in Atmospheric Turbulence (SonicBAT) Program were to develop and validate, via research flight experiments under a range of realistic atmospheric conditions, one numeric turbulence model research code and one classic turbulence model research code using traditional N-wave booms in the presence of atmospheric turbulence, and to apply these models to assess the effects of turbulence on the levels of shaped sonic booms predicted from low boom aircraft designs. The SonicBAT program has successfully investigated sonic boom turbulence effects through the execution of flight experiments at two NASA centers, Armstrong Flight Research Center (AFRC) and Kennedy Space Center (KSC), collecting a comprehensive set of acoustic and atmospheric turbulence data that were used to validate the numeric and classic turbulence models developed. The validated codes were incorporated into the PCBoom sonic boom prediction software and used to estimate the effect of turbulence on the levels of shaped sonic booms associated with several low boom aircraft designs. The SonicBAT program was a four year effort that consisted of turbulence model development and refinement throughout the entire period as well as extensive flight test planning that culminated with the two research flight tests being conducted in the second and third years of the program. The SonicBAT team, led by Wyle, includes partners from the Pennsylvania State University, Lockheed Martin, Gulfstream Aerospace, Boeing, Eagle Aeronautics, Technical & Business Systems, and the Laboratory of Fluid Mechanics and Acoustics (France). A number of collaborators, including the Japan Aerospace Exploration Agency, also participated by supporting the experiments with human and equipment resources at their own expense. Three NASA centers, AFRC, Langley Research Center (LaRC), and KSC were essential to the planning and conduct of the experiments. The experiments involved precision flight of either an F-18A or F-18B executing steady, level passes at supersonic airspeeds in a turbulent atmosphere to create sonic boom signatures that had been distorted by turbulence. The flights spanned a range of atmospheric turbulence conditions at NASA Armstrong and Kennedy in order to provide a variety of conditions for code validations. The SonicBAT experiments at both sites were designed to capture simultaneous F-18A or F-18B onboard flight instrumentation data, high fidelity ground based and airborne acoustic data, surface and upper air meteorological data, and additional meteorological data from ultrasonic anemometers and SODARs to determine the local atmospheric turbulence and boundary layer height

Miracle seeds: Biased expectations, complementary input use, and the dynamics of smallholder technology adoption

To fully benefit from new agricultural technologies like improved seed varieties, significant investment in complementary inputs such as fertilizers and pesticides, and practices such as systematic planting, irrigation, and weeding are also required. Farmers may fail to recognize the importance of these complements, leading to unsatisfactory crop yields and outputs and, eventually, dis-adoption of the variety. We provide a simple model of biased expectations, complementary input use and technology adoption and test its predictions using a field experiment among smallholder maize farmers in eastern Uganda. We find that pointing out the importance of complementary investments using a short, engaging video effectively deters some farmers from using commercial improved varieties. Consistent with the theoretical model, we find some evidence that this behavior change emanates from increased knowledge and expectations that are more in line with realized outcomes

Coupling angle variability in healthy and patellofemoral pain runners

Background Patellofemoral pain is hypothesized to result in less joint coordination variability. The ability to relate coordination variability to patellofemoral pain pathology could have many clinical uses; however, evidence to support its clinical application is lacking. The aim was to determine if vector coding's coupling angle variability, as a measure of joint coordination variability, was less for runners with patellofemoral pain than healthy controls as is commonly postulated. Methods Nineteen female recreational runners with patellofemoral pain and eleven healthy controls performed a treadmill acclimation protocol then ran at a self-selected pace for 15 min. 3-D kinematics, force plate kinetics, knee pain and rating of perceived exertion were recorded each minute. Data were selected for the: pain group at the highest pain reached (pain � 3/10) in a non-exerted state (exertion < 14/20), and; non-exerted healthy group from the eleventh minute. Coupling angle variability was calculated over several portions of the stride for six knee-ankle combinations during five non-consecutive strides. Findings 46 of 48 coupling angle variability measures were greater for the pain group, with 7 significantly greater (P <.05). Interpretation These findings oppose the theory that less coupling angle variability is indicative of a pathological coordinate state during running. Greater coupling angle variability may be characteristic of patellofemoral pain in female treadmill running when a larger threshold of pain is reached than previously observed. A predictable and directional response of coupling angle variability measures in relation to knee pathology is not yet clear and requires further investigation prior to considerations for clinical utility. © 2013 Elsevier Ltd

Biomarkers of Lead Exposure and DNA Methylation within Retrotransposons

Background: DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. Objective: In this study we compared associations between lead biomarkers and DNA methylation. Methods: We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Results: Overall mean global methylation (± SD) was 26.3 ± 1.0 as measured by Alu and 76.8 ± 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (β = −0.25; p less than 0.01) but not Alu (β = −0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. Conclusion: Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells

Background: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Results: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024–2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND. Conclusions: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations

Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10-8) and PPP4R4/SERPINA1 (P = 1.0131028) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, ~0.6), and accounted for a mean 0.9–1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function

Towards an Economy of Higher Education

This paper draws a distinction between ways thinking and acting, and hence of policy and practice in higher education, in terms of different kinds of economy: economies of exchange and economies of excess. Crucial features of economies of exchange are outlined and their presence in prevailing conceptions of teaching and learning is illustrated. These are contrasted with other possible forms of practice, which in turn bring to light the nature of an economy of excess. In more philosophical terms, and to expand on the picture, economies of excess are elaborated with reference, first, to the understanding of alterity in the work of Emmanuel Levinas and, second, to the idea of Dionysian intensity that is to be found in Nietzsche. In the light of critical comment on some current directions in policy and practice, the implications of these ways of thinking for the administrator, the teacher and the student in higher education are explored