Ideologies of time: How elite corporate actors engage the future

Our paper deals with how elite corporate actors in a Western capitalist-democratic society conceive of and prepare for the future. Paying attention to how senior officers of ten important Danish companies make sense of the future will help us to identify how particular temporal narratives are ideologically marked. This ideological dimension offers a common sense frame that is structured around a perceived inevitability of capitalism, a market economy as the basic organizational structure of the social and economic order, and an assumption of confident access to the future. Managers envisage their organization?s future and make plans for organizational action in a space where ?business as usual? reigns, and there is little engagement with the future as fundamentally open; as a time-yet-to-come. In using a conceptual lens inspired by the work of Fredric Jameson, we first explore the details of this presentism and a particular colonization of the future, and then linger over small disruptions in the narratives of our interviewees which point to what escapes or jars their common sense frame, explore the implicit meanings they assign to their agency, and also find clues and traces of temporal actions and strategies in their narratives that point to a subtly different engagement with time

C-Type Natriuretic Peptide (CNP) Inhibition of Interferon-γ-Mediated Gene Expression in Human Endothelial Cells In Vitro

Cardiovascular diseases, including atherosclerosis, now account for more deaths in the Western world than from any other cause. Atherosclerosis has a chronic inflammatory component involving Th1 pro-inflammatory cytokines such as IFN-γ, which is known to induce endothelial cell inflammatory responses. On the other hand CNP, which acts via its receptors to elevate intracellular cGMP, is produced by endothelium and endocardium and is upregulated in atherosclerosis. It is believed to be protective, however its role in vascular inflammation is not well understood. The aim of this study was to investigate the effects of CNP on human endothelial cell inflammatory responses following IFN-γ stimulation. Human umbilical vein endothelial cells were treated with either IFN-γ (10 ng/mL) or CNP (100 nm), or both in combination, followed by analysis by flow cytometry for expression of MHC class I and ICAM-1. IFN-γ significantly increased expression of both molecules, which was significantly inhibited by CNP or the cGMP donor 8-Bromoguanosine 3’,5’-cyclic monophosphate (1 µm). CNP also reduced IFN-γ mediated kynurenine generation by the IFN-γ regulated enzyme indoleamine-2,3-deoxygenase (IDO). We conclude that CNP downmodulates IFN-γ induced pro-inflammatory gene expression in human endothelial cells via a cGMP-mediated pathway. Thus, CNP may have a protective role in vascular inflammation and novel therapeutic strategies for CVD based on upregulation of endothelial CNP expression could reduce chronic EC inflammation

Processing and analysis methods for transonic cavity flow

This paper focuses on the localisation of noise sources in transonic cavity flows. Beamforming is used to estimate the pressure fluctuations inside a resonant transonic cavity, showing the localisation of the main sources of noise using an acoustic array and also combining it with a mean flow-field. The influence of the microphone array position, density, and shape is investigated. The presented method models the noise propagation with simple assumptions that are easily applicable to wind tunnel testing and may help localise the noise sources from complex geometries without intrusive methods

RANS-based Aerodynamic Shape Optimization of a Blended-Wing-Body Aircraft

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106453/1/AIAA2013-2586.pd

Strategies for Solving High-Fidelity Aerodynamic Shape Optimization Problems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140440/1/6.2014-2594.pd

Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients.

BACKGROUND: Critically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function. METHODS: Primary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty. Validation cohort: Four-centre randomized controlled trial. INTERVENTION: FES cycling for 60-90min/day. ANALYSES: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation. RESULTS: Positively enriched pathways between healthy volunteers and ICU participants were "stress response", "response to stimuli" and "protein metabolism", in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were "FOXO-mediated transcription" (admission = 0.48 ± 0.94, day 7 = - 0.47 ± 1.04 mean log2 fold change; P = 0.042), "Fatty acid metabolism" (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2 fold change; P = 0.042) and "Interleukin-1 processing" (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2 fold change; P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P  0.05). CONCLUSIONS: Intramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone

Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid

5,6-Dimethylxanthenone-4-acetic acid, synthesised in this laboratory, reduces tumour blood flow, both in mice and in patients on Phase I trial. We used TUNEL (TdT-mediated dUTP nick end labelling) assays to investigate whether apoptosis induction was involved in its antivascular effect. 5,6-Dimethylxanthenone-4-acetic acid induced dose-dependent apoptosis in vitro in HECPP murine endothelial cells in the absence of up-regulation of mRNA for tumour necrosis factor. Selective apoptosis of endothelial cells was detected in vivo in sections of Colon 38 tumours in mice within 30 min of administration of 5,6-Dimethylxanthenone-4-acetic acid (25 mg kg−1). TUNEL staining intensified with time and after 3 h, necrosis of adjacent tumour tissue was observed. Apoptosis of central vessels in splenic white pulp was also detected in tumour-bearing mice but not in mice without tumours. Apoptosis was not observed in liver tissue. No apoptosis was observed with the inactive analogue 8-methylxanthenone-4-acetic acid. Positive TUNEL staining of tumour vascular endothelium was evident in one patient in a Phase I clinical trial, from a breast tumour biopsy taken 3 and 24 h after infusion of 5,6-Dimethylxanthenone-4-acetic acid (3.1 mg m−2). Tumour necrosis and the production of tumour tumour necrosis factor were not observed. No apoptotic staining was seen in tumour biopsies taken from two other patients (doses of 3.7 and 4.9 mg m−2). We conclude that 5,6-Dimethylxanthenone-4-acetic acid can induce vascular endothelial cell apoptosis in some murine and human tumours. The action is rapid and appears to be independent of tumour necrosis factor induction

MHC immunoevasins: protecting the pathogen reservoir in infection

Alteration of antigen recognition by T cells as result of insufficient major histocompatibility complex (MHC)-dependent antigen-presenting function has been observed in many cases of infections, particularly in in vitro systems. To hide themselves from an efficient immune response, pathogens may act on MHC-related functions at three levels: (i) by limiting the number of potential antigens that can be presented to naive T cells; (ii) by synthesizing proteins which directly affect MHC cell-surface expression; and (iii) by altering the normal intracellular pathway of peptide loading on MHC. Here, we review examples of pathogens' action on each single step of MHC function and we suggest that the result of these often synergistic actions is both a limitation of the priming of naive T cells and, more importantly, a protection of the pathogen's reservoir from the attack of primed T cells. The above mechanisms may also generate a skewing effect on immune effector mechanisms, which helps preserving the reservoir of infection from sterilization by the immune system

Carma CO observations of three extremely metal-poor, star-forming galaxies

We present sensitive CO (J = 1 0) emission line observations of the three metal-poor dwarf irregular galaxies Leo P (Z ∼ 3% Zo), Sextans A (Z ∼ 7.5% Zo), and Sextans B (Z ∼ 7.5% Zo), all obtained with the Combined Array for Millimeter-wave Astronomy interferometer. While no CO emission was detected, the proximity of the three systems allows us to place very stringent (4σ) upper limits on the CO luminosity (LCO) in these metal-poor galaxies. We find the CO luminosities to be LCO < 2900 K km s-1 pc2 for Leo P, LCO < 12,400 K km s-1 pc2 for Sextans A, and LCO < 9700 K km s-1 pc2 for Sextans B. Comparison of our results with recent observational estimates of the factor for converting between LCO and the mass of molecular hydrogen, as well as theoretical models, provides further evidence that either the CO-to-H2 conversion factor increases sharply as metallicity decreases, or that stars are forming in these three galaxies very efficiently, requiring little molecular hydroge