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Article ; Online: A semi-empirical model of the aerodynamics of manoeuvring insect flight.

Walker, Simon M / Taylor, Graham K

2021 Volume 18, Issue 177, Page(s) 20210103

Abstract: Blade element modelling provides a quick analytical method for estimating the aerodynamic forces produced during insect flight, but such models have yet to be tested rigorously using kinematic data recorded from free-flying insects. This is largely ... ...

Abstract	Blade element modelling provides a quick analytical method for estimating the aerodynamic forces produced during insect flight, but such models have yet to be tested rigorously using kinematic data recorded from free-flying insects. This is largely because of the paucity of detailed free-flight kinematic data, but also because analytical limitations in existing blade element models mean that they cannot incorporate the complex three-dimensional movements of the wings and body that occur during insect flight. Here, we present a blade element model with empirically fitted aerodynamic force coefficients that incorporates the full three-dimensional wing kinematics of manoeuvring
MeSH term(s)	Animals ; Biomechanical Phenomena ; Diptera ; Flight, Animal ; Insecta ; Models, Biological ; Wings, Animal
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2021.0103
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Auditory sensory range of male mosquitoes for the detection of female flight sound.

Nakata, Toshiyuki / Simões, Patrício / Walker, Simon M / Russell, Ian J / Bomphrey, Richard J

Journal of the Royal Society, Interface

2022 Volume 19, Issue 193, Page(s) 20220285

Abstract: Male mosquitoes detect and localize conspecific females by their flight-tones using the Johnston's organ (JO), which detects antennal deflections under the influence of local particle motion. Acoustic behaviours of mosquitoes and their JO physiology have ...

Abstract	Male mosquitoes detect and localize conspecific females by their flight-tones using the Johnston's organ (JO), which detects antennal deflections under the influence of local particle motion. Acoustic behaviours of mosquitoes and their JO physiology have been investigated extensively within the frequency domain, yet the auditory sensory range and the behaviour of males at the initiation of phonotactic flights are not well known. In this study, we predict a maximum spatial sensory envelope for flying
MeSH term(s)	Animals ; Culex/physiology ; Culicidae/physiology ; Female ; Flight, Animal/physiology ; Male ; Sound
Language	English
Publishing date	2022-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2022.0285
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Article ; Online: Motor output and control input in flapping flight: a compact model of the deforming wing kinematics of manoeuvring hoverflies.

Nagesh, Indira / Walker, Simon M / Taylor, Graham K

Journal of the Royal Society, Interface

2019 Volume 16, Issue 161, Page(s) 20190435

Abstract: Insects are conventionally modelled as controlling flight by varying a few summary kinematic parameters that are defined on a per-wingbeat basis, such as the stroke amplitude, mean stroke angle and mean wing pitch angle. Nevertheless, as insects have ... ...

Abstract	Insects are conventionally modelled as controlling flight by varying a few summary kinematic parameters that are defined on a per-wingbeat basis, such as the stroke amplitude, mean stroke angle and mean wing pitch angle. Nevertheless, as insects have tens of flight muscles and vary their kinematics continuously, the true dimension of their control input space is likely to be much higher. Here, we present a compact description of the deforming wing kinematics of 36 manoeuvring
MeSH term(s)	Animals ; Biomechanical Phenomena ; Diptera/physiology ; Flight, Animal/physiology ; Models, Biological ; Principal Component Analysis ; Wings, Animal/physiology
Language	English
Publishing date	2019-12-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2019.0435
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Article ; Online: Mechanism and spectrum of inhibition of a 4’-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses

Gordon, Calvin J. / Walker, Simon M. / Tchesnokov, Egor P. / Kocincova, Dana / Pitts, Jared / Siegel, Dustin S. / Perry, Jason K. / Feng, Joy Y. / Bilello, John P. / Götte, Matthias

bioRxiv

Abstract: The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide ... ...

Abstract	The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5′-triphosphate (TP) metabolite of a 4ʹ-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4ʹ-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1′-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1ʹ-cyano and 4ʹ-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
Keywords	covid19
Language	English
Publishing date	2024-04-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.04.22.590607
Database	COVID19

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Article ; Online: Mechanism and spectrum of inhibition of a 4′-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses

Gordon, Calvin J. / Walker, Simon M. / Tchesnokov, Egor P. / Kocincova, Dana / Pitts, Jared / Siegel, Dustin S. / Perry, Jason K. / Feng, Joy Y. / Bilello, John P. / Gotte, Matthias

bioRxiv

Abstract	The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5′-triphosphate (TP) metabolite of a 4ʹ-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4ʹ-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1′-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1ʹ-cyano and 4ʹ-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
Keywords	covid19
Language	English
Publishing date	2024-04-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.04.22.590607
Database	COVID19

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Article ; Online: (with research data) Smart wing rotation and trailing-edge vortices enable high frequency mosquito flight.

Bomphrey, Richard J / Nakata, Toshiyuki / Phillips, Nathan / Walker, Simon M

Nature

2017 Volume 544, Issue 7648, Page(s) 92–95

Abstract: Mosquitoes exhibit unusual wing kinematics; their long, slender wings flap at remarkably high frequencies for their size (>800 Hz)and with lower stroke amplitudes than any other insect group. This shifts weight support away from the translation-dominated, ...

Abstract	Mosquitoes exhibit unusual wing kinematics; their long, slender wings flap at remarkably high frequencies for their size (>800 Hz)and with lower stroke amplitudes than any other insect group. This shifts weight support away from the translation-dominated, aerodynamic mechanisms used by most insects, as well as by helicopters and aeroplanes, towards poorly understood rotational mechanisms that occur when pitching at the end of each half-stroke. Here we report free-flight mosquito wing kinematics, solve the full Navier-Stokes equations using computational fluid dynamics with overset grids, and validate our results with in vivo flow measurements. We show that, although mosquitoes use familiar separated flow patterns, much of the aerodynamic force that supports their weight is generated in a manner unlike any previously described for a flying animal. There are three key features: leading-edge vortices (a well-known mechanism that appears to be almost ubiquitous in insect flight), trailing-edge vortices caused by a form of wake capture at stroke reversal, and rotational drag. The two new elements are largely independent of the wing velocity, instead relying on rapid changes in the pitch angle (wing rotation) at the end of each half-stroke, and they are therefore relatively immune to the shallow flapping amplitude. Moreover, these mechanisms are particularly well suited to high aspect ratio mosquito wings.
MeSH term(s)	Air Movements ; Animals ; Biomechanical Phenomena ; Culex/anatomy & histology ; Culex/physiology ; Flight, Animal/physiology ; Hydrodynamics ; Male ; Reproducibility of Results ; Rotation ; Wings, Animal/anatomy & histology ; Wings, Animal/physiology
Language	English
Publishing date	2017-03-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature21727
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 9: Show issues
Zs.MO 244: Show issues

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Book: Hospital and health care security in Australia

Walker, Simon M

2009

Author's details	Simon M. Walker
MeSH term(s)	Hospitals ; Security Measures/standards ; Safety Management
Keywords	Australia
Language	English
Size	x, 247 p. :, ill.
Publisher	Connley Walker
Publishing place	Melbourne
Document type	Book
Note	Includes index.
ISBN	9780957907416 ; 0957907419
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Aerodynamic imaging by mosquitoes inspires a surface detector for autonomous flying vehicles.

Nakata, Toshiyuki / Phillips, Nathan / Simões, Patrício / Russell, Ian J / Cheney, Jorn A / Walker, Simon M / Bomphrey, Richard J

Science (New York, N.Y.)

2019 Volume 368, Issue 6491, Page(s) 634–637

Abstract: Some flying animals use active sensing to perceive and avoid obstacles. Nocturnal mosquitoes exhibit a behavioral response to divert away from surfaces when vision is unavailable, indicating a short-range, mechanosensory collision-avoidance mechanism. We ...

Abstract	Some flying animals use active sensing to perceive and avoid obstacles. Nocturnal mosquitoes exhibit a behavioral response to divert away from surfaces when vision is unavailable, indicating a short-range, mechanosensory collision-avoidance mechanism. We suggest that this behavior is mediated by perceiving modulations of their self-induced airflow patterns as they enter a ground or wall effect. We used computational fluid dynamics simulations of low-altitude and near-wall flights based on in vivo high-speed kinematic measurements to quantify changes in the self-generated pressure and velocity cues at the sensitive mechanosensory antennae. We validated the principle that encoding aerodynamic information can enable collision avoidance by developing a quadcopter with a sensory system inspired by the mosquito. Such low-power sensing systems have major potential for future use in safer rotorcraft control systems.
MeSH term(s)	Accidents, Aviation/prevention & control ; Aircraft ; Animals ; Arthropod Antennae/physiology ; Bionics ; Computer Simulation ; Culicidae/physiology ; Flight, Animal/physiology ; Night Vision/physiology ; Robotics/methods
Language	English
Publishing date	2019-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aaz9634
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: Operation of the alula as an indicator of gear change in hoverflies.

Walker, Simon M / Thomas, Adrian L R / Taylor, Graham K

Journal of the Royal Society, Interface

2011 Volume 9, Issue 71, Page(s) 1194–1207

Abstract: The alula is a hinged flap found at the base of the wings of most brachyceran Diptera. The alula accounts for up to 10 per cent of the total wing area in hoverflies (Syrphidae), and its hinged arrangement allows the wings to be swept back over the thorax ...

Abstract	The alula is a hinged flap found at the base of the wings of most brachyceran Diptera. The alula accounts for up to 10 per cent of the total wing area in hoverflies (Syrphidae), and its hinged arrangement allows the wings to be swept back over the thorax and abdomen at rest. The alula is actuated via the third axillary sclerite, which is a component of the wing hinge that is involved in wing retraction and control. The third axillary sclerite has also been implicated in the gear change mechanism of flies. This mechanism allows rapid switching between different modes of wing kinematics, by imposing or removing contact with a mechanical stop limiting movement of the wing during the lower half of the downstroke. The alula operates in two distinct states during flight-flipped or flat-and we hypothesize that its state indicates switching between different flight modes. We used high-speed digital video of free-flying hoverflies (Eristalis tenax and Eristalis pertinax) to investigate whether flipping of the alula was associated with changes in wing and body kinematics. We found that alula state was associated with different distributions of multiple wing kinematic parameters, including stroke amplitude, stroke deviation angle, downstroke angle of incidence and timing of supination. Changes in all of these parameters have previously been linked to gear change in flies. Symmetric flipping of the alulae was associated with changes in the symmetric linear acceleration of the body, while asymmetric flipping of the alulae was associated with asymmetric angular acceleration of the body. We conclude that the wings produce less aerodynamic force when the alula is flipped, largely as a result of the accompanying changes in wing kinematics. The alula changes state at mid-downstroke, which is the point at which the gear change mechanism is known to come into effect. This transition is accompanied by changes in the other wing kinematic parameters. We therefore find that the state of the alula is linked to the same parameters as are affected by the gear change mechanism. We conclude that the state of the alula does indeed indicate the operation of different flight modes in Eristalis, and infer that a likely mechanism for these changes in flight mode is the gear change mechanism.
MeSH term(s)	Adaptation, Physiological/physiology ; Animals ; Computer Simulation ; Diptera/physiology ; Feedback, Physiological/physiology ; Flight, Animal/physiology ; Models, Biological ; Physical Exertion/physiology ; Stress, Mechanical ; Wings, Animal/physiology
Language	English
Publishing date	2011-11-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2011.0617
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa.

Walker, Simon M / Cox, Edward / Revill, Paul / Musiime, Victor / Bwakura-Dangarembizi, Mutsa / Mallewa, Jane / Cheruiyot, Priscilla / Maitland, Kathryn / Ford, Nathan / Gibb, Diana M / Walker, A Sarah / Soares, Marta

Journal of the International AIDS Society

2020 Volume 23, Issue 3, Page(s) e25469

Abstract: Introduction: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including ... ...

Abstract	Introduction: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standard-prophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm Conclusions: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices.
MeSH term(s)	AIDS-Related Opportunistic Infections/economics ; AIDS-Related Opportunistic Infections/prevention & control ; Adolescent ; Adult ; Africa ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/economics ; Anti-HIV Agents/therapeutic use ; Antifungal Agents/administration & dosage ; Antifungal Agents/therapeutic use ; Antigens, Fungal/analysis ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cohort Studies ; Cost-Benefit Analysis ; Cryptococcus/immunology ; Female ; Fluconazole/therapeutic use ; HIV Infections/drug therapy ; HIV Infections/economics ; HIV Infections/mortality ; HIV Infections/prevention & control ; Humans ; Male ; Post-Exposure Prophylaxis/economics ; Quality-Adjusted Life Years
Chemical Substances	Anti-HIV Agents ; Antifungal Agents ; Antigens, Fungal ; Fluconazole (8VZV102JFY)
Language	English
Publishing date	2020-03-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2467110-1
ISSN	1758-2652 ; 1758-2652
ISSN (online)	1758-2652
ISSN	1758-2652
DOI	10.1002/jia2.25469
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