1,721,961 research outputs found
Development of second generation cyclic peptide inhibitors of hypoxia inducible factors
No full textHypoxia-inducible factors (HIFs) are heterodimeric transcription factors that function as the master regulators of the cellular response to low oxygen concentrations. HIFs upregulate the expression of genes that promote growth and initiate metabolic changes, which subsequently aid survival and reoxygenation under these conditions. Tumour cores often contain oxygen-depleted regions that exhibit high levels of HIF activity, subsequently triggering this biochemical response. HIF activity is thought to be associated with the aggressive growth, metastasis and greater persistence phenotypes exhibited by such tumours. As such the inhibition of the HIF pathway is considered to be an attractive target in the development of new cancer therapeutics.This work presents a set of novel cyclic peptide inhibitors of the HIF pathway, which function by disrupting a key protein-protein interaction between the α and β subunits of the HIF heterodimeric transcription factor. These peptides were selected for their ability to inhibit both isoforms of the HIF-α subunit. The affinity of the peptides for each of these was determined and from this, a lead peptide was identified.The structure-activity relationship of the lead peptide with the protein target has been explored, through use of alanine scanning and incorporation of unnatural amino acid derivatives. This approach has led to the identification of an optimised HIF inhibitor that exhibits a binding affinity below the μM threshold.A series of in vitro assays to detect HIF dimerization have also been designed and utilised. The effects of the inhibitory peptides on these systems has also been investigated
Tribological behaviour diagnostic and fault detection of mechanical seals based on acoustic emission measurements
No full textAcoustic emission (AE) has been studied for monitoring the condition of mechanical seals by many researchers, however to the best knowledge of the authors, typical fault cases and their effects on tribological behaviour of mechanical seals have not yet been successfully investigated. In this paper, AE signatures from common faults of mechanical seals are studied in association with tribological behaviour of sealing gap to develop more reliable condition monitoring approaches. A purpose-built test rig was employed for recording AE signals from the mechanical seals under healthy and faulty conditions. The collected data was then processed using time domain and frequency domain analysis methods. The study has shown that AE signal parameters: root mean squared (RMS) along with AE spectrum, allows fault conditions including dry running, spring out and defective seal faces to be diagnosed under a wide range of operating conditions. However, when mechanical seals operate around their transition point, conventional signal processing methods may not allow a clear separation of the fault conditions from the healthy baseline. Therefore an auto-regressive (AR) model has been developed on recorded AE signals to classify different fault conditions of mechanical seals and satisfactory results have been perceived
Condition Monitoring of Reciprocating Compressor Based on Acoustic Imaging
No full textAcoustical condition monitoring is capable of extracting the characteristics of operating machinery without installation of accelerometer. With the development of acoustic signal processing, the acoustical condition monitoring reactivates in recent years. One of the efficient technologies is acoustic imaging, which can localize and visualize the sound source position in different frequency band to suppress the noise interference. In this paper, the acoustic imaging technology is applied to perform condition monitoring of reciprocating compressor. The discharge valve leakage (DVL) of second stage cylinder are taken as an instance of compressor leakage. This experiment shows the potential to detect leakages of compressor. Firstly, the sound source positions of an operating reciprocating compressor are computed by an acoustic camera in different frequency bands. Secondly, the root mean square (RMS) are compared with baseline in certain frequency band, particularly the specific frequency of sound only emitted from around faulty position. The result shows that the RMS of DVL in specific frequency band would increase significantly.</p
Modelling acoustic emissions generated by tribological behaviour of mechanical seals for condition monitoring and fault detection
Full text linkAcoustic emission (AE) signals are useful for the condition monitoring of mechanical seals as tribological regimes affect the AE signatures. In this paper the investigation develops a mathematical model that can predict the energy of an AE signal under different tribological regimes. The developed model has been validated with experimental studies and satisfactory results have been perceived. Therefore, the model has strong potential to be used to obtain tribological behaviour of mechanical seals and hence develop a reliable and accurate condition monitoring system under varying operating conditions.</p
Planetary landers and entry probes
No full textContentsPreface; Acknowledgements; Part I. Engineering Issues Specific to Entry Probes, Landers or Penetrators: 1. Mission goals and system engineering; 2. Accommodation, launch, cruise and arrival from orbit or interplanetary trajectory; 3. Entering atmospheres; 4. Descent through an atmosphere; 5. Descent to an airless body; 6. Planetary balloons, aircraft, submarines and cryobots; 7. Arrival at a surface; 8. Thermal control of landers and entry probes; 9. Power systems; 10. Communication and tracking of entry probes; 11. Radiation environment; 12. Surface activities: arms, drills, moles and mobility; 13. Structures; 14. Contamination of spacecraft and planets; Part II. Previous Atmosphere/Surface Vehicles and Their Payloads: 15. Destructive impact probes; 16. Atmospheric entry probes; 17. Pod landers; 18. Legged landers; 19. Payload delivery penetrators; 20. Small body surface missions; Part III. ‘Case Studies’: 21. Surveyor landers; 22. Galileo probe; 23. Huygens; 24. Mars Pathfinder and Sojourner; 25. Deep Space 2 Mars microprobes; 26. Rosetta lander Philae; 27. Mars exploration rovers: Spirit and Opportunity; Appendix: Some key parameters for bodies in the Solar System; List of acronyms; Bibliography; References; Index
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Effect of Operating Parameters on the Acoustic Emission Induced by Polymer Surface Shearing in Fused Filament Fabrication
No full textTo implement in-process monitoring of 3D printing manufacturing and ensure the quality of printed workpieces, this paper investigates the mechanism of Acoustic Emission (AE) generated from the process of viscous flow shearing during material deposition. Firstly, a flow shearing force equation is derived to consider the dynamic effect caused by wavy surfaces, fluctuating pressures, and rheological properties. Then, deposition distance, material temperature, and flow rate are investigated to correlate the time–frequency characteristics of AE signals with various sources. It has been found deposition distance and material viscosity are two main factors affecting flow shearing behaviors and AE characteristics. At last, experiments were designed and conducted based on the control instructions. The results show an obvious correlation between AE signal and the running parameters, verifying the predictability of the shearing force equation for the main parameters. These findings have paved the foundation for further research on monitoring the extrusion process of additive manufacturing materials using AE technology.</p
Multisensory Data-Based Fault Diagnosis of Induction Motors Using 1D and 2D Convolutional Neural Networks
No full textInduction motors are widely employed across various industries, which necessitates the development of an effective fault diagnosis system to prevent unplanned downtime. Lately, there has been a notable emphasis on deep learning techniques, primarily attributed to their capacity for directly extracting features from unprocessed data. In this study, we collected multisensory signals (vibration, current, voltage, and speed) from an induction motor test stand under diverse operating conditions, including healthy, outer bearing fault, and shaft misalignment. Seven combinations of the multisensory data were employed to train 1D and 2D Convolutional Neural Network (CNN) architectures for motor fault classification. A comparative analysis was undertaken to evaluate the diagnostic accuracy, number of parameters, and computational time of the 1D and 2D CNN models. The results reveal that the best performance was achieved when the 1D and 2D CNN models were trained solely on the motor’s vibration signals. Additionally, the 2D CNN model slightly outperformed the 1D CNN in terms of its overall validation accuracy under different multisensory signal combinations.</p
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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