Multiaxis thrust vectoring using axisymmetric nozzles and postexit vanes on an F/A-18 configuration vehicle

A ground-based investigation was conducted on an operational system of multiaxis thrust vectoring using postexit vanes around an axisymmetric nozzle. This thrust vectoring system will be tested on the NASA F/A-18 High Alpha Research Vehicle (HARV) aircraft. The system provides thrust vectoring capability in both pitch and yaw. Ground based data were gathered from two separate tests at NASA Langley Research Center. The first was a static test in the 16-foot Transonic Tunnel Cold-Jet Facility with a 14.25 percent scale model of the axisymmetric nozzle and the postexit vanes. The second test was conducted in the 30 by 60 foot wind tunnel with a 16 percent F/A-18 complete configuration model. Data from the two sets are being used to develop models of jet plume deflection and thrust loss as a function of vane deflection. In addition, an aerodynamic interaction model based on plume deflection angles will be developed. Results from the scale model nozzle test showed that increased vane deflection caused exhaust plume turning. Aerodynamic interaction effects consisted primarily of favorable interaction of moments and unfavorable interaction of forces caused by the vectored jet plume

Exploring the associations shared by mood, pain-related attention and pain outcomes related to sleep disturbance in a chronic pain sample

OBJECTIVE: Sleep disturbance in chronic pain is common, occurring in two-thirds of patients. There is a complex relationship between chronic pain and sleep; pain can disrupt sleep and poor sleep can exaggerate pain intensity. This may have an impact on both depressive symptoms and attention to pain. This study aims to evaluate the relationship between chronic pain and sleep, and the role of mood and attention. METHODS: Chronic pain patients, recruited from a secondary care outpatient clinic, completed self-report measures of pain, sleep, depressive symptoms and attention to pain. Hierarchical regression and structural equation modelling were used to explore the relationships between these measures. Participants (n = 221) were aged between 20 and 84 (mean = 52) years. RESULTS: The majority of participants were found to be ‘poor sleepers’ (86%) with increased pain severity, depressive symptoms and attention to pain. Both analytical approaches indicated that sleep disturbance is indirectly associated with increased pain severity Instead the relationship shared by sleep disturbance and pain severity was further associated with depressive symptoms and attention to pain. CONCLUSIONS: Our results indicate that sleep disturbance may contribute to clinical pain severity indirectly though changes in mood and attention. Prospective studies exploring lagged associations between these constructs could have critical information relevant to the treatment of chronic pain

Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.

Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-β treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid β-oxidation. TGF-β treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-β-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-β treatment

Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation

The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m

PKA-activated ApAF–ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation

Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF–ApC/EBP heterodimer transactivates enhancer response element–containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF–ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF

In vivo parasitological measures of artemisinin susceptibility

Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24