The nature of operating flight loads and their effect on propulsion system structures

Past diagnostics studies revealed the primary causes of performance deterioration of high by-pass turbofan engines to be flight loads, erosion, and thermal distortion. The various types of airplane loads that are imposed on the engine throughout the lifetime of an airplane are examined. These include flight loads from gusts and maneuvers and ground loads from takeoff, landing, and taxi conditions. Clarification is made in definitions of the airframer's limit and ultimate design loads and the engine manufacturer's operating design loads. Finally, the influence of these loads on the propulsion system structures is discussed

Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons

Human acute and inflammatory pain requires the expression of voltage-gated sodium channel Nav1.7 but its significance for neuropathic pain is unknown. Here we show that Nav1.7 expression in different sets of mouse sensory and sympathetic neurons underlies distinct types of pain sensation. Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses to heat. In contrast, heat-evoked pain is retained when SCN9A is deleted only in Nav1.8-positive nociceptors. Surprisingly, responses to the hotplate test, as well as neuropathic pain, are unaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in both sensory and sympathetic neurons abolishes these pain sensations and recapitulates the pain-free phenotype seen in humans with SCN9A loss-of-function mutations. These observations demonstrate an important role for Nav1.7 in sympathetic neurons in neuropathic pain, and provide possible insights into the mechanisms that underlie gain-of-function Nav1.7-dependent pain conditions

Specific involvement of atypical PKCζ/PKMζ in spinal persistent nociceptive processing following peripheral inflammation in rat.

BACKGROUND: Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP), a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCζ/PKMζ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. RESULTS: Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ζ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs) following formalin administration. In addition, Complete Freund's Adjuvant (CFA)-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCζ/PKMζ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCζ/PKMζ in dorsal horn neurons, specifically PKMζ phosphorylation in formalin rats. Finally, inhibition of PKCζ/PKMζ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. CONCLUSIONS: These results suggest that PKCζ, especially PKMζ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation

Foreground removal from CMB temperature maps using an MLP neural network

One of the main obstacles in extracting the Cosmic Microwave Background (CMB) signal from observations in the mm-submm range is the foreground contamination by emission from galactic components: mainly synchrotron, free-free and thermal dust emission. Due to the statistical nature of the intrinsic CMB signal it is essential to minimize the systematic errors in the CMB temperature determinations. Following the available knowledge of the spectral behavior of the galactic foregrounds simple, power law-like spectra have been assumed. The feasibility of using a simple neural network for extracting the CMB temperature signal from the combined CMB and foreground signals has been investigated. As a specific example, we have analysed simulated data, like that expected from the ESA Planck Surveyor mission. A simple multilayer perceptron neural network with 2 hidden layers can provide temperature estimates, over more than 80 percent of the sky, that are to a high degree uncorrelated with the foreground signals. A single network will be able to cover the dynamic range of the Planck noise level over the entire sky.Comment: Accepted for publication in Astrophysics and Space Scienc

Fine motor difficulties: the need for advocating for the role of occupational therapy in schools

Background: Fine motor difficulties can impact on the academic, social and emotional development of a student. Aim: The aims of this paper are to: (i) investigate the need for support to students experiencing fine motor&nbsp; difficulties from the perspective of their classroom teachers, and (ii) report on the level of knowledge teachers have in regard to the role of occupational therapists in supporting students with fine motor difficulties.&nbsp; Methods: Fifteen teachers from a stratified random sample of public schools within two regions of Victoria, Australia, were interviewed in this qualitative, grounded theory investigation. Results: Results showed that the current level of support for students with fine motor difficulties is inadequate. Conclusion: Occupational therapists in Victoria need to advocate their role in developing the fine motor skills of students at both an organisational and an individual level in order to increase the access of students with fine motor difficulties to occupational therapy services. <br /

Critical Review of Theoretical Models for Anomalous Effects (Cold Fusion) in Deuterated Metals

We briefly summarize the reported anomalous effects in deuterated metals at ambient temperature, commonly known as "Cold Fusion" (CF), with an emphasis on important experiments as well as the theoretical basis for the opposition to interpreting them as cold fusion. Then we critically examine more than 25 theoretical models for CF, including unusual nuclear and exotic chemical hypotheses. We conclude that they do not explain the data.Comment: 51 pages, 4 Figure

Unlocking value from machines: business models and the industrial internet of things

In this article we argue that the Industrial Internet of Things (IIoT) offers new opportunities and harbors threats that companies are not able to address with existing business models. Entrepreneurship and Transaction Cost Theories are used to explore the conditions for designing nonownership business models for the emerging IIoT with its implications for sharing uncertain opportunities and downsides, and for transforming these uncertainties into business opportunities. Nonownership contracts are introduced as the basis for business model design and are proposed as an architecture for the productive sharing of uncertainties in IIoT manufacturing networks. The following three main types of IIoT-enabled business models were identified: (1) Provision of manufacturing assets, maintenance and repair, and their operation, (2) innovative information and analytical services that help manufacturing (e.g., based on artificial intelligence, big data, and analytics), and (3) new services targeted at end-users (e.g., offering efficient customization by integrating end-users into the manufacturing and supply chain ecosystem)

Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/-) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2-/-mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2(-/-)) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2(-/-) mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability