The introduction of the bacterium Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Evidence of a reduction in dengue case ...incidence following field releases of wMel-infected Ae. aegypti has been reported previously from a cluster randomised controlled trial in Indonesia, and quasi-experimental studies in Indonesia and northern Australia.
Following pilot releases in 2015-2016 and a period of intensive community engagement, deployments of adult wMel-infected Ae. aegypti mosquitoes were conducted in Niterói, Brazil during 2017-2019. Deployments were phased across four release zones, with a total area of 83 km2 and a residential population of approximately 373,000. A quasi-experimental design was used to evaluate the effectiveness of wMel deployments in reducing dengue, chikungunya and Zika incidence. An untreated control zone was pre-defined, which was comparable to the intervention area in historical dengue trends. The wMel intervention effect was estimated by controlled interrupted time series analysis of monthly dengue, chikungunya and Zika case notifications to the public health surveillance system before, during and after releases, from release zones and the control zone. Three years after commencement of releases, wMel introgression into local Ae. aegypti populations was heterogeneous throughout Niterói, reaching a high prevalence (>80%) in the earliest release zone, and more moderate levels (prevalence 40-70%) elsewhere. Despite this spatial heterogeneity in entomological outcomes, the wMel intervention was associated with a 69% reduction in dengue incidence (95% confidence interval 54%, 79%), a 56% reduction in chikungunya incidence (95%CI 16%, 77%) and a 37% reduction in Zika incidence (95%CI 1%, 60%), in the aggregate release area compared with the pre-defined control area. This significant intervention effect on dengue was replicated across all four release zones, and in three of four zones for chikungunya, though not in individual release zones for Zika.
We demonstrate that wMel Wolbachia can be successfully introgressed into Ae. aegypti populations in a large and complex urban setting, and that a significant public health benefit from reduced incidence of Aedes-borne disease accrues even where the prevalence of wMel in local mosquito populations is moderate and spatially heterogeneous. These findings are consistent with the results of randomised and non-randomised field trials in Indonesia and northern Australia, and are supportive of the Wolbachia biocontrol method as a multivalent intervention against dengue, chikungunya and Zika.
Traditional vector control approaches such as source reduction and insecticide spraying have limited effect on reducing Aedes aegypti population. The endosymbiont Wolbachia is pointed as a promising ...tool to mitigate arbovirus transmission and has been deployed worldwide. Models predict a rapid increase on the frequency of Wolbachia-positive Ae. aegypti mosquitoes in local settings, supported by cytoplasmic incompatibility (CI) and high maternal transmission rate associated with the wMelBr strain.
Wolbachia wMelBr strain was released for 20 consecutive weeks after receiving >87% approval of householders of the isolated community of Tubiacanga, Rio de Janeiro. wMelBr frequency plateued~40% during weeks 7-19, peaked 65% but dropped as releases stopped. A high (97.56%) maternal transmission was observed. Doubling releases and deploying mosquitoes with large wing length and low laboratory mortality produced no detectable effects on invasion trend. By investigating the lab colony maintenance procedures backwardly, pyrethroid resistant genotypes in wMelBr decreased from 68% to 3.5% after 17 generations. Therefore, we initially released susceptible mosquitoes in a local population highly resistant to pyrethroids which, associated with the over use of insecticides by householders, ended jeopardizing Wolbachia invasion. A new strain (wMelRio) was produced after backcrossing wMelBr females with males from field to introduce mostly pyrethroid resistance alleles. The new strain increased mosquito survival but produced relevant negative effects on Ae. aegypti fecundity traits, reducing egg clutche size and egg hatch. Despite the cost on fitness, wMelRio successful established where wMelBr failed, revealing that matching the local population genetics, especially insecticide resistance background, is critical to achieve invasion.
Local householders support was constantly high, reaching 90% backing on the second release (wMelRio strain). Notwithstanding the drought summer, the harsh temperature recorded (daily average above 30°C) did not seem to affect the expression of maternal transmission of wMel on a Brazilian background. Wolbachia deployment should match the insecticide resistance profile of the wild population to achieve invasion. Considering pyrethroid-resistance is a widely distributed phenotype in natural Ae. aegypti populations, future Wolbachia deployments must pay special attention in maintaining insecticide resistance in lab colonies for releases.
•Formalize disjunctive linear separation conditions for aircraft conflict resolution.•Characterize pairwise aircraft conflict-free trajectories based on velocity bounds.•Propose exact solution ...methods for the 2D aircraft conflict resolution problem.•Lexicographic optimization approach for extended problem with flight level changes.•Show that the proposed methods outperform state-of-the-art approaches.
We address the aircraft conflict resolution problem in air traffic control. We introduce new mixed-integer programming formulations for aircraft conflict resolution with speed, heading and altitude control which are based on disjunctive linear separation conditions. We first examine the two-dimensional aircraft conflict resolution problem with speed and heading control represented as continuous decision variables. We show that the proposed disjunctive linear separation conditions are equivalent to the classical nonlinear conditions for aircraft separation. Further, we characterise conflict-free trajectories based on aircraft velocity bounds and propose a simple pre-processing algorithm to identify aircraft pairs which are either always conflict-free, or which cannot be separated using speed and heading control only. We then incorporate altitude control and propose a lexicographic optimisation formulation that aims to minimise the number of flight level changes before resolving outstanding conflicts via two-dimensional velocity control. The proposed mixed-integer programming formulations are nonconvex, and we propose convex relaxations, decomposition methods and constraint generation algorithms to solve the two-dimensional and lexicographic optimisation formulations to guaranteed optimality. Numerical experiments on four types of conflict resolution benchmarking instances are conducted to test the performance of the proposed mixed-integer formulations. Further, the proposed method is compared against two benchmarks based on state-of-the-art approaches for the aircraft conflict resolution problem. Our numerical results show that the proposed method largely outperforms both benchmarks in terms of runtime and is able to solve significantly more instances to global optimality.
The recent association of Zika virus with cases of microcephaly has sparked a global health crisis and highlighted the need for mechanisms to combat the Zika vector, Aedes aegypti mosquitoes. ...Wolbachia pipientis, a bacterial endosymbiont of insect, has recently garnered attention as a mechanism for arbovirus control. Here we report that Aedes aegypti harboring Wolbachia are highly resistant to infection with two currently circulating Zika virus isolates from the recent Brazilian epidemic. Wolbachia-harboring mosquitoes displayed lower viral prevalence and intensity and decreased disseminated infection and, critically, did not carry infectious virus in the saliva, suggesting that viral transmission was blocked. Our data indicate that the use of Wolbachia-harboring mosquitoes could represent an effective mechanism to reduce Zika virus transmission and should be included as part of Zika control strategies.
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•Mosquitoes harboring Wolbachia were resistant to current circulating Zika virus isolates•Zika virus prevalence, intensity, and disseminated infection were reduced•Saliva from Wolbachia-harboring mosquitoes did not contain infectious Zika virus
Strategies to combat Zika virus (ZIKV) and its mosquito vector are urgently needed. Dutra et al. report that Wolbachia-carrying mosquitoes are highly resistant to ZIKV and display reduced virus prevalence and intensity. Saliva from Wolbachia-carrying mosquitoes did not contain infectious virus, suggesting the possibility to block ZIKV transmission.
Thermally activated delayed fluorescence (TADF) has recently emerged as one of the most attractive methods for harvesting triplet states in metal-free organic materials for application in organic ...light emitting diodes (OLEDs). A large number of TADF molecules have been reported in the literature with the purpose of enhancing the efficiency of OLEDs by converting non-emissive triplet states into emissive singlet states. TADF emitters are able to harvest both singlets and triplet states through fluorescence (prompt and delayed), the latter due to the thermally activated reverse intersystem crossing mechanism that allows up-conversion of low energy triplet states to the emissive singlet level. This allows otherwise pure fluorescent OLEDs to overcome their intrinsic limit of 25% internal quantum efficiency (IQE), which is imposed by the 1:3 singlet-triplet ratio arising from the recombination of charges (electrons and holes). TADF based OLEDS with IQEs close to 100% are now routinely fabricated in the green spectral region. There is also significant progress for blue emitters. However, red emitters still show relatively low efficiencies. Despite the significant progress that has been made in recent years, still significant challenges persist to achieve full understanding of the TADF mechanism and improve the stability of these materials. These questions need to be solved in order to fully implement TADF in OLEDs and expand their application to other areas. To date, TADF has been exploited mainly in the field of OLEDs, but applications in other areas, such as sensing and fluorescence microscopies, are envisaged. In this review, the photophysics of TADF molecules is discussed, summarising current methods to characterise these materials and the current understanding of the TADF mechanism in various molecular systems.
Chemical modification of phenothiazine‐benzophenone derivatives tunes the emission behavior from triplet states by selecting the geometry of the intramolecular charge transfer (ICT) state. A ...fundamental principle of planar ICT (PICT) and twisted ICT (TICT) is demonstrated to obtain selectively either room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF), respectively. Time‐resolved spectroscopy and time‐dependent density functional theory (TD‐DFT) investigations on polymorphic single crystals demonstrate the roles of PICT and TICT states in the underlying photophysics. This has resulted in a RTP molecule OPM, where the triplet states contribute with 89 % of the luminescence, and an isomeric TADF molecule OMP, where the triplet states contribute with 95 % of the luminescence.
Rapid and efficient utilization of triplet states to generate room temperature phosphorescence (RTP) or highly efficient thermally activated delayed fluorescence (TADF) is achieved by structural modification to give a planar or twisted intramolecular charge transfer (PICT or TICT) geometry, respectively.
The kinetics of thermally activated delayed fluorescence (TADF) is investigated in dilute solutions of organic materials with application in blue light-emitting diodes (OLEDs). A method to accurately ...determine the energy barrier (ΔEa) and the rate of reverse intersystem crossing (kRisc) in TADF emitters is developed, and applied to investigate the triplet-harvesting mechanism in blue-emitting materials with large singlet-triplet energy gap (ΔEST). In these materials, triplet-triplet annihilation (TTA) is the dominant mechanism for triplet harvesting; however, above a threshold temperature TADF is able to compete with TTA and give enhanced delayed fluorescence. Evidence is obtained for the interplay between the TTA and the TADF mechanisms in these materials.
Sequence alignments are the foundations of life science research, but most innovation so far focuses on optimal alignments, while information derived from suboptimal solutions is ignored. We argue ...that one optimal alignment per pairwise sequence comparison is a reasonable approximation when dealing with very similar sequences but is insufficient when exploring the biodiversity of the protein universe at tree-of-life scale. To overcome this limitation, we introduce pairwise alignment-safety to uncover the amino acid positions robustly shared across all suboptimal solutions. We implement EMERALD, a software library for alignment-safety inference, and apply it to 400k sequences from the SwissProt database.
Understanding the delayed fluorescence mechanism behind the creation of emissive singlets from the non‐emissive triplets in exciplexes is vital for the fabrication of highly efficient blue ...fluorescent emitters, and subsequent white light applications. In this article we report the spectroscopic investigation of the exciplex formed between 4,4′,4′′‐tris3‐methylphenyl(phenyl)aminotriphenylamine (m‐MTDATA) and 2‐(biphenyl‐4‐yl)‐5‐(4‐tert‐butylphenyl)‐1,3,4‐oxadiazole (PBD) in a 50:50 blended film. The mechanism behind extra singlet production in the blend is of E‐type nature, that is, "thermally activated" delayed fluorescence. The exciplex singlet‐triplet energy splitting is estimated to be around 5 meV, smaller than previously estimated at ≈ 50 meV. The absence of a well defined separation between prompt emission and emission components with very long lifetimes, >100 ns, is indicative of such a small exchange energy, and arises through multiple cycling between the resonant singlet and triplet manifolds before eventually being emitted from a singlet state. An observed redshift of the exciplex emission with time and increasing temperature is attributed to different exciplex species being formed between the m‐MTDATA and PBD molecules.
Extra singlet production via thermally activated delayed fluorescence in the exciplex formed between m‐MTDATA and PBD is investigated. The exciplex singlet‐triplet splitting is estimated to be very small at ≈ 5 meV, leading to a multiple cycling between the resonant singlet and triplet manifolds of exciplex before eventually being emitted from a singlet state.
We investigated the influence of diaphragmatic activation control (diaphC) on the relaxation rate, contractile properties and electrical activity of the inspiratory muscles of healthy subjects. ...Assessments were performed non-invasively using the sniff inspiratory pressure test (SNIP) and surface electromyography, respectively. Twenty-two subjects (10 men and 12 women) performed 10 sniff maneuvers in two different days: with and without diaphC instructions. For the SNIP test with diaphC, the subjects were instructed to perform intense activation of the diaphragm. The tests with the best SNIP values were used for analysis. The maneuver with diaphC when compared to the maneuver without diaphC exhibited significant lower values for: SNIP (p <0.01), maximum relaxation rate (MRR) (p <0.01), maximum rate of pressure development (MRPD) (p <0.01), contraction times (CT) (p = 0.02) and electrical activity of the sternocleidomastoid (SCM) (p <0.01), scalene (SCL) (p = 0.01) and intercostal (CI) (p = 0.03) muscles. In addition, the decay constant (tau, tau) and relaxation time (½ RT) did not present any changes. The diaphragmatic control performed during the SNIP test influences the inspiratory pressure and the contractile properties of inspiratory muscles. This occurs due to changes in the pattern of muscle recruitment, which change force velocity characteristics of the test. Thus, instruction on diaphC should be encouraged for better performance of the SNIP test and for evaluation targeting the diaphragm muscle activity.
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