Propagation of sound from aircraft ground operations

Atmospheric absorption effects on sound propagation losses during aircraft ground operation

The propagation of sound from airport ground operations

Noise measurements of sound propagation related to jet aircraft takeoff

HARMONIC GENERATION *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72100/1/j.1749-6632.1965.tb20242.x.pd

Twist1 Is a TNF-Inducible Inhibitor of Clock Mediated Activation of Period Genes.

BACKGROUND: Activation of the immune system affects the circadian clock. Tumor necrosis factor (TNF) and Interleukin (IL)-1β inhibit the expression of clock genes including Period (Per) genes and the PAR-bZip clock-controlled gene D-site albumin promoter-binding protein (Dbp). These effects are due to cytokine-induced interference of E-box mediated transcription of clock genes. In the present study we have assessed the two E-box binding transcriptional regulators Twist1 and Twist2 for their role in cytokine induced inhibition of clock genes. METHODS: The expression of the clock genes Per1, Per2, Per3 and of Dbp was assessed in NIH-3T3 mouse fibroblasts and the mouse hippocampal neuronal cell line HT22. Cells were treated for 4h with TNF and IL-1β. The functional role of Twist1 and Twist2 was assessed by siRNAs against the Twist genes and by overexpression of TWIST proteins. In luciferase (luc) assays NIH-3T3 cells were transfected with reporter gene constructs, which contain a 3xPer1 E-box or a Dbp E-box. Quantitative chromatin immunoprecipitation (ChIP) was performed using antibodies to TWIST1 and CLOCK, and the E-box consensus sequences of Dbp (CATGTG) and Per1 E-box (CACGTG). RESULTS: We report here that siRNA against Twist1 protects NIH-3T3 cells and HT22 cells from down-regulation of Period and Dbp by TNF and IL-1β. Overexpression of Twist1, but not of Twist2, mimics the effect of the cytokines. TNF down-regulates the activation of Per1-3xE-box-luc, the effect being prevented by siRNA against Twist1. Overexpression of Twist1, but not of Twist2, inhibits Per1-3xE-box-luc or Dbp-E-Box-luc activity. ChIP experiments show TWIST1 induction by TNF to compete with CLOCK binding to the E-box of Period genes and Dbp. CONCLUSION: Twist1 plays a pivotal role in the TNF mediated suppression of E-box dependent transactivation of Period genes and Dbp. Thereby Twist1 may provide a link between the immune system and the circadian timing system

Bidirectional and context-dependent changes in theta and gamma oscillatory brain activity in noradrenergic cell-specific Hypocretin/Orexin receptor 1-KO mice.

Noradrenaline (NA) and hypocretins/orexins (HCRT), and their receptors, dynamically modulate the circuits that configure behavioral states, and their associated oscillatory activities. Salient stimuli activate spiking of locus coeruleus noradrenergic (NA <sup>LC</sup> ) cells, inducing NA release and brain-wide noradrenergic signalling, thus resetting network activity, and mediating an orienting response. Hypothalamic HCRT neurons provide one of the densest input to NA <sup>LC</sup> cells. To functionally address the HCRT-to-NA connection, we selectively disrupted the Hcrtr1 gene in NA neurons, and analyzed resulting (Hcrtr1 <sup>Dbh-CKO</sup> ) mice', and their control littermates' electrocortical response in several contexts of enhanced arousal. Under enforced wakefulness (EW), or after cage change (CC), Hcrtr1 <sup>Dbh-CKO</sup> mice exhibited a weakened ability to lower infra-θ frequencies (1-7 Hz), and mount a robust, narrow-bandwidth, high-frequency θ rhythm (~8.5 Hz). A fast-γ (55-80 Hz) response, whose dynamics closely parallelled θ, also diminished, while β/slow-γ activity (15-45 Hz) increased. Furthermore, EW-associated locomotion was lower. Surprisingly, nestbuilding-associated wakefulness, inversely, featured enhanced θ and fast-γ activities. Thus HCRT-to-NA signalling may fine-tune arousal, up in alarming conditions, and down during self-motivated, goal-driven behaviors. Lastly, slow-wave-sleep following EW and CC, but not nestbuilding, was severely deficient in slow-δ waves (0.75-2.25 Hz), suggesting that HCRT-to-NA signalling regulates the slow-δ rebound characterizing sleep after stress-associated arousal

Function of the fully conserved residues Asp99, Tyr52 and Tyr73 in phospholipase A2

In the active centre of pancreatic phospholipase A2 His48 is at hydrogen-bonding distance to Asp99. This Asp-His couple is assumed to act together with a water molecule as a catalytic triad. Asp99 is also linked via an extended hydrogen bonding system to the side chains of Tyr52 and Tyr73. To probe the function of the fully conserved Asp99, Tyr52 and Tyr73 residues in phospholipase A2, the Asp99 residue was replaced by Asn, and each of the two tyrosines was separately replaced by either a Phe or a Gln. The catalytic and binding properties of the Phe52 and Phe73 mutants did not change significantly relative to the wild-type enzyme. This rules out the possibility that either one of the two Tyr residues in the wild-type enzyme can function as an acyl acceptor or proton donor in catalysis. The Gln73 mutant could not be obtained in any significant amounts probably due to incorrect folding. The Gln52 mutant was isolated in low yield. This mutant showed a large decrease in catalytic activity while its substrate binding was nearly unchanged. The results suggest a structural role rather than a catalytic function of Tyr52 and Tyr73. Substitution of asparagine for aspartate hardly affects the binding constants for both monomeric and micellar substrate analogues. Kinetic characterization revealed that the Asn99 mutant has retained no less than 65% of its enzymatic activity on the monomeric substrate rac 1,2-dihexanoyldithio-propyl-3-phosphocholine, probably due to the fact that during hydrolysis of monomeric substrate by phospholipase A2 proton transfer is not the rate-limiting step. The Asp to Asn substitution decreases the catalytic rate on micellar 1,2-dioctanoyl-sn-glycero-3-phosphocholine 25-fold. To explain this remaining activity we suggest that in the mutant the Asn99 orients His48 in the same way as Asp99 orients His48 in native phospholipase A2 and that the lowered activity is caused by a reduced stabilization of the transition state

Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer

Background Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. Methods The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. Results The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3–11.9Gy compared to radiotherapy alone (D95 = 45.0–45.5Gy). Conclusions This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting

Airborne investigations of clear-air turbulence with laser radars

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33443/1/0000846.pd

Prevalence of scoliosis and impaired pulmonary function in patients with type III osteogenesis imperfecta

Purpose: Osteogenesis Imperfecta (OI) is a rare group of congenital genetic disorders that consists of a collagen synthesis defect. The most severe phenotype is type III OI. Characterized by progressive bone deformity, fragility and pulmonary impairment, causing significant morbidity and mortality. Also, multilevel spine deformities are observed, such as scoliosis. The literature on the pathophysiology of pulmonary impairment in relation to scoliosis in these patients is scarce and conflicting. This study aims to determine the prevalence of scoliosis and its relation to pulmonary function in type III OI patients. Methods: This retrospective cohort study took place between April 2020 and November 2021. Forty-two patients with type III OI were included. Anterior–posterior spine radiographs were evaluated for scoliosis. Pulmonary function was assessed using spirometry and partial pressure of carbon dioxide. Results: All 42 patients had scoliosis, with a mean curve of 66° (95% CI of range). Vital lung capacity was decreased, compared to a non-OI population (mean 1.57 L). This was correlated to the degree of scoliosis (st. β − 0.40, P = 0.03), especially in increasing thoracic curves. Restrictive lung pathophysiology was shown in our study population with a mean FEV1/FVC ratio of 0.85. Conclusions: Increasing thoracic scoliosis was correlated with decreased vital lung capacity in our study population of type III OI patients. High FEV1/FVC ratios found in this study population show restrictive lung pathophysiology. Therefore, it is plausible that the pulmonary impairment found in type III OI patients is a combined issue, partly associated to scoliosis and partly intrinsic to OI